Rebif News: 52 articles

The REGARD Study – A Head-to-Head Comparison of Rebif® 44 mcg (interferon beta-1a) and Copaxone® (glatiramer acetate)

2009-01-09T11:28:00.000-08:00

The results of the REGARD* study were presented at the recent 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The REGARD study compared Rebif (interferon beta-1a) 44 mcg and Copaxone (glatiramer acetate) over 96 weeks in patients with relapsing-remitting MS. Principal investigator, Daniel Mikol, MD, PhD, from the Department of Neurology at the University of Michigan, Ann Arbor, provides some first-hand insight into the findings of the study.

Q. What was the overall rationale for the REGARD study and what information were you hoping it would provide?

Dr Mikol: The REGARD study was the first well-controlled, randomized, head-to-head study between any interferon-beta and glatiramer acetate. The interferon-beta preparation used in the study was Rebif, and the study was sponsored by EMD Serono and Pfizer, co-marketers of Rebif in the US.

It's well accepted that the best way to gauge the relative efficacies of 2 agents in a disease such as relapsing-remitting MS is to compare them head-to-head. Prior to this study, the only way to try to compare interferon-beta and glatiramer acetate was by using results from the individual placebo-controlled studies — different trials with different patient populations, and trial designs that differed somewhat from one study to another. So in conducting the REGARD study, the intent was to use the same population of patients and the same study design to determine whether one agent was superior to the other.

Q: You mentioned the importance of having the same population for both therapies — what exactly were the entry criteria for patients enrolled in the REGARD study?

Dr Mikol: The main inclusion criterion was relapsing-remitting MS. The study was planned in 2003 and began enrollment in 2004, so we used the 2001 McDonald criteria¹ for MS diagnosis which distinguishes it from previous trials that used the Poser criteria. Patients had to be between 18 and 60 years of age, had to have had at least one attack during the previous 12 months, and had to have a baseline disability rating (EDSS^†) between 0 and 5.5. Patients could not have progressive MS, and they could not have used any interferon-beta or glatiramer acetate prior to study entry.

Q: Could you describe the overall study design?

Dr Mikol: The REGARD study was a multicenter, 96-week, open-label study. Patients were randomized to Rebif 44 mcg or Copaxone. Patients knew which of the 2 agents they received. However, evaluation of the results was blinded, both by MRI and by the neurological assessor — the neurological assessor rating EDSS, either at scheduled visits or unscheduled visits at the time of possible relapse, did not know which treatment the patient had been assigned to receive. MRIs were also analyzed in a blinded fashion.

A total of 81 clinical centers in 14 different countries took part in the study. The initial design called for 736 patients. This number of patients was expected to provide 80% power to detect a 30% relative difference in the primary outcome measure. With this subject size, it was projected that approximately 460 patients would have at least one relapse during the course of the study; 764 subjects were actually enrolled (386 Rebif 44 mcg; 378 Copaxone).

An open-label, randomized, multicenter, comparative, assessor-blinded study
Planned sample size of 736 patients provides 80% power to detect 30% relative increase in primary parameter (time to first relapse at 96 weeks)
Assumes 460 patients will have at least one relapse over 96 weeks

IFN = Interferon.

Patients were seen at baseline and randomized to receive either Rebif 44 mcg tiw SC or Copaxone 20 mg qd SC. The main clinic visits for neurological assessment were conducted at 6-month intervals, when patients underwent EDSS assessment. All patients had a baseline brain MRI, and approximately 60% of patients underwent serial MRIs every 6 months.

Q: Were there any differences between the patients in the 2 arms of the study?

Dr Mikol: For the most part, there were no differences at baseline — in both groups, patients were about 37 years of age, and roughly 70% of patients in each group were female. The mean EDSS at entry was 2.3 in both groups, which is similar to other recent relapsing-remitting MS trials. Gadolinium-enhancing volume and T2 lesion volume were not significantly different between groups.

A statistically significant difference was that more patients in the Copaxone group (48%) had received steroid treatment in the 6 months prior to the study than patients in the Rebif group (40%; P=0.023). Another difference that was observed regards the proportion of patients who had experienced more than one relapse in the 24 months prior to enrollment. While not statistically significant it is important to note that 71% of Copaxone-treated patients had experienced more than one relapse, compared with 60% of Rebif-treated patients (P=0.057). It is difficult to extrapolate how this difference might have affected outcome, if at all.

Q: What was the primary endpoint of the REGARD study, and what was the rationale for selecting that endpoint?

Dr Mikol: The primary endpoint in the REGARD study was time to first relapse during the 96-week treatment period. Many other relapsing-remitting MS trials have used relapse rate, but those trials have typically used a placebo comparator. This endpoint was selected because it was thought to be clinically meaningful. I believe that the type of patient entering this study (ie, just beginning treatment) has concerns about their future disease course, such that delaying the time to relapse is very important.

Q: So with respect to the primary endpoint of time to first relapse, what did you see in the REGARD study?

Dr Mikol: In terms of the primary endpoint — time to first relapse — there was no significant difference between the 2 agents over the course of 96 weeks. The hazard ratio, which is a measure of the relative chance of experiencing a relapse on one agent versus the other, was just very slightly in favor of Rebif (0.943). But the confidence interval was very broad, and there was certainly no statistically significant difference between the 2 agents (95% CI, 0.74-1.21; P=0.643).

Time to first relapse (primary endpoint)

Time to first relapse: hazard ratio (95% CI) = 0.943 (0.74, 1.21)
This was not statistically significant (P=0.643), so the study did not meet its primary endpoint
460/736 patients (63%) were expected to have ≥1 relapse
However, only 258/764 patients (34%) experienced ≥1 relapse
- Approximately 45% fewer relapses than expected (258/460)

CI = confidence interval.

What was unexpected in this study was the small number of relapses overall. Based on previous studies, it was expected that around 63% of patients would have had at least one relapse over the course of 96 weeks, and in fact only 34% had any relapse — a little over half of the number that were expected. As a result, the study was not powered sufficiently to show a potential difference between the 2 agents with respect to this outcome measure.

Q: Why do you think there were fewer relapses overall than the 63% that you expected?

Dr Mikol: Well, that is an interesting and important question, and we don't have a definitive answer. If you follow the trend in clinical studies with interferon-beta or glatiramer acetate over recent years, the relapse rate seems to be declining over time, with other recent studies yielding lower relapse rates than have been seen historically. In addition, there are a number of possible reasons why we saw fewer relapses in this study compared to earlier trials, which reflects study design. Whereas the REGARD study required just one relapse in the previous 12 months, many previous trials required subjects to have had at least 2 relapses in the previous 2 years. So we may have biased towards a less active group of patients in REGARD.

Moreover, we now have a number of available treatment options for relapsing-remitting MS, as well as an increasing number of clinical trials. Patients in the REGARD study had to be naïve to treatment with interferon-beta or glatiramer acetate. In earlier trials, these treatments were not as widely available as they are now, especially in some parts of the world, so at that time treatment-naïve patients may have had very active disease. Today, however, you would expect the majority of patients with active disease to already be on one of these treatments. So it is quite probable that we were trying to detect a treatment benefit in a population that had a relatively low level of disease activity. The drop-out rate was also higher than expected, which means that complete data were available from fewer patients than we had originally projected.

Q: What did the REGARD study show with respect to the safety of these medications?

Dr Mikol: Neither drug appeared to offer any safety advantage over the other. There were no unexpected adverse events, and both agents were rather comparable in terms of the incidence of any treatment-related adverse events. The overall withdrawal rate from the study was higher than historical trials — 17% (21% on Rebif and 14% on Copaxone). Many of the incremental drop-outs in the Rebif group were patients who were lost to follow-up or whose reason for withdrawing from the study was described as "other," rather than any specific drug-related effect. In the Rebif group, 23 patients (6%) discontinued treatment due to adverse events, and in the Copaxone group, 18 patients (5%) discontinued treatment due to adverse events.

Around 95% of adverse events in both groups were mild to moderate, meaning that about 5% in each group were more severe.

Certain adverse events were more commonly seen in the Rebif group, and others were more commonly seen in the Copaxone group. In the Rebif group, not surprisingly, flu-like side effects, headache, and myalgias were more common, as well as elevated ALT levels. Patients in the Copaxone treatment arm more commonly experienced injection-site pruritis, injection-site swelling, and injection-site induration, as well as dyspnea and postinjection systemic reactions. 19 Copaxone patients (5.1%) reported postinjection reactions vs 0 Rebif patients. Otherwise, there were no statistically significant differences with respect to adverse events between the 2 treatment arms, including depression, which was not significantly different.

Adverse events leading to discontinuation

In the Rebif group, 23 patients (6.0%) discontinued treatment due to 40 events*

"Influenza-like illness" resulted in significantly more discontinuations than in the Copaxone group (1.6% versus 0% of patients; P=0.031)

In the Copaxone group, 18 patients (4.8%) discontinued treatment due to 35 events*

"Immediate postinjection reaction" resulted in significantly more discontinuations than in the Rebif group (1.3% versus 0% of patients; P=0.030)

* Does not include discontinuations due to pregnancy.

Q: Finally, then, how do you feel the REGARD study advances what is known today about optimal treatment approaches for relapsing-remitting MS?

Dr Mikol: This study is important because it is the first large, randomized, controlled, head-to-head comparison between any interferon-beta and Copaxone in relapsing-remitting MS. As far as advancing knowledge about the relative clinical efficacy of Rebif and Copaxone, I don't think that we can draw any definitive conclusions with respect to the primary endpoint in this study. With far fewer observed relapses than expected overall, the study was not sufficiently powered to see the projected difference in time to first relapse for one treatment arm versus the other. I think that investigators in other studies will have to take into account the possibility that treatment-naïve patients who are available for enrollment in clinical trials today may not have as active disease as patients who were enrolled in previous studies, conducted at a time when effective treatment options were not widely available.

Ultimately, in order to show a treatment effect on a clinical outcome (ie, relapses) in a clinical trial, there must be a sufficient number of those events. If the McDonald criteria are employed, as they were in this study, patients who have had just one clinical attack (and demonstrated MRI change) can be enrolled. However, it is not necessarily possible to predict how such patients are likely to behave during the course of the study: Patients who have had multiple attacks, but only one in the past year, may not have another attack during the course of the study. As a result, there may need to be some rethinking about what criteria are most appropriate when enrolling subjects into a 2-year clinical study.

Medscape

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2008-12-26T19:49:00.000-08:00

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2006-12-29T11:45:00.000-08:00

Put Out the Fires of MS - Today, we have an array of “hoses” to combat this disease [Review of Optometry]...MORE
".....Beginning MS treatment as soon as possible is very important; over time, nerve damage caused by multiple sclerosis in the brain and spinal cord becomes permanent and leads to physical disability or cognitive impairment. The treatment of MS focuses mainly on decreasing the rate and severity of relapse, reducing the number of MS lesions, delaying the progression of the disease, and providing symptomatic relief for the patient. (A discussion of the symptoms, relapses and remissions of MS is beyond the scope of this column.)

Over time, nerve damage caused by MS in the brain and spinal cord becomes permanent and leads to physical disability or cognitive impairment.

Advances in interferon therapy have assisted greatly in the management of impairment from MS. Interferons are substances produced by the body to combat viral infections and regulate the immune system.

Recombinant interferon therapies have proven to be effective in reducing relapses and accumulation of brain lesions over time.2-10 The overall reduction in risk of relapse appears to be nearly 30%.2 Patients who have a lower baseline relapse rate prior to the initiation of interferon therapy seem to have a more favorable prognosis.4 Adverse reactions associated with these medications include flu-like symptoms, increased spasticity of lower limbs, site injection reactions and systemic allergic reactions.7

All MS treatments are given by injection. There are currently four available MS drugs:
• Avonex (interferon beta-1a, Biogen Idec). This is indicated for patients who have relapsing forms of MS to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. Avonex appears to be most successful in patients who have experienced a first clinical episode of focal neurologic deficit and have MRI features consistent with MS.4

Avonex is injected intramuscularly once a week. It decreases the rate of relapse and the development of new lesions. It also delays the progression of motor and cognitive disability.

• Rebif (interferon beta-1a, Serono and Pfizer). Similar to Avonex, this interferon is injected subcutaneously three times per week. Rebif also reduces the rate of relapse and slows the progression of disability.3

• Betaseron (interferon beta-1b, Berlex). This drug is injected subcutaneously three to four times per week. It has similar indications and actions of Avonex and Rebif.4,5

• Copaxone (glatiramer acetate, Teva Pharmaceutical). This is actually a mixture of amino acids. It is injected subcutaneously seven times per week. Exactly how Copaxone works is unclear, but it is believed to modify the immune process that causes MS.7 In one study, nearly all patients who used Copaxone (with a mean disease duration of 15 years) remained ambulatory after 10 years.10 Patients who withdrew from treatment had greater disability than patients who continued treatment.10

Patients can develop resistance to these drugs if they endogenously produce neutralizing antibodies that inactivate MS therapy. Although the significance of neutralizing antibodies is not fully understood, it is thought that they can render MS treatments less effective over time.11 So, the potential for development of neutralizing antibodies is an important consideration in determining whether to initiate treatment.

Optic neuritis has long been seen as a calling card of MS. While we typically suspected underlying MS in patients who had optic neuritis, we were averse to actually diagnosing MS in these patients years ago because we could offer them no effective treatment. Today, however, we have several therapies that reduce the relapse rate of the disease and slow the progression and development of both motor and cognitive disabilities. Because the clinical course of MS can now be altered, it is imperative to diagnose the patient as quickly as possible so that immunomodulatory therapies can be offered"

2006-12-29T11:41:00.000-08:00

(CHILD ON REBIF)
For kids, MS itself just half the battle | Chicago Tribune

(previous) Improving clinical care and support services for young people is another objective of the centers, whose Midwest location is the Mayo Clinic in Rochester, Minn.

"The biggest single problem these kids have is they don't know anyone else like them," said Maria Milazzo, a pediatric nurse practitioner at the Stony Brook MS center.

learning to adjust

Nicole Caron was so scared after being diagnosed with MS last year at 15 that she didn't tell any of her friends what was wrong--or even admit the truth of her illness to herself. A basketball and soccer player, Nicole first felt numbness in her fingers, then extreme fatigue. Within a few months, she began getting excruciating headaches, blurred vision and pain behind her left eye.

The final diagnosis came after a brain scan and a spinal tap, but relief at knowing what was wrong was quickly followed by fear and denial.

"I didn't want to believe anything was wrong," said Nicole, who lives in North Attleboro, Mass., and is being treated at Massachusetts General Hospital. "I thought if I kept it to myself it would be all right. And I knew everyone at school would gossip, and I didn't to be the center of attention."

But the more Nicole concealed her worries, the lonelier she became. "I felt like a bad person because I wasn't telling anyone the truth," she said. After a month, she began letting friends know what was going on, but none of them had ever heard of MS.

Twice a week, Nicole left school for doctors' appointments; once, a teacher commented in class on her excused absences. "I started to cry, I was so upset," said Nicole, who gives herself daily injections of the drug Copaxone to help stall the progress of MS. Several weeks later, she disclosed her illness to the teacher.

For her mother, Judy Caron, the hardest part is accepting the unpredictability of MS, with symptoms that can come and go without warning.

"As a parent, you always try to fix everything for your children, but with this disease you have absolutely no control," she said.

In south suburban Country Club Hills, Carol Jones--Tiffany's mom--repeats a similar lament: "What's so scary about MS is, you can't tell what the future holds. You just don't know day to day what tomorrow is going to be."

Coping, with help

Tiffany's symptoms first surfaced in July 2005; after multiple visits with doctors and medical tests, a definitive diagnosis came a year later. In between, this slim dancer and pompom squad member with big, dark eyes couldn't understand why her arms and legs were going numb or why she suddenly would stumble or drop a cup.

"It makes you feel so uncertain and so afraid," said the soft-spoken girl, who started thrice weekly injections of the drug Rebif in November.

For support, Tiffany and her mom turned to a group of adults with MS who meet monthly in nearby Crete.

"It's really helpful to know what other people go through," but many of the group members are in wheelchairs and "I was thinking one day that could be me," she said.

At school, Tiffany told a few close friends about her illness early this fall but kept it concealed from other classmates and her teachers. She felt conflicted. She wanted people at school to know how her life had changed, but she didn't want to tell them.

Then, an assignment for her anatomy class became an inspiration to come forward. The teacher, by coincidence, had asked her to write a report on multiple sclerosis.

Standing before her classmates, Tiffany spoke of her fear, her faith and her confusion about what it means to stand on the edge of adulthood, trying to accept a lifelong illness.

"At times, I still feel like MS is taking over my life. I'm still struggling with that," she said. But "I have to tell myself to stop wondering what will become of me. I know that no matter what, I won't give up."

2006-12-29T10:33:00.000-08:00

Serono Announces Initiation of the Reflex Trial to Evaluate New Formulation of Rebif(R) in Patients at Risk of Developing Multiple Sclerosis
First Trial Assessing Therapeutic Benefit of Two Different Dosage Regimens of Disease Modifying Therapy in People With First Clinical Symptoms Suggesting Multiple Sclerosis

GENEVA, Switzerland -- Serono (virt-x: SEO and NYSE: SRA) announced today the initiation of a Phase III clinical trial to evaluate the effect of two dosage regimens of the new formulation of Rebif(R) (interferon beta-1a 44 mcg, three times a week or once a week) on the time to conversion to multiple sclerosis (MS) in people with first clinical symptoms suggestive of the disease. The trial, called the REFLEX study (REbif FLEXible dosing in early MS), will involve 480 patients considered at risk of developing MS because of a recently experienced isolated demyelinating event and of typical magnetic resonance imaging (MRI) brain scans.

"It has been demonstrated that early treatment with interferon-beta can reduce the risk of developing multiple sclerosis. Optimizing the impact of such treatment on development of irreversible neurological damage and ascertainment of long term outcomes is still subject of active experimental and clinical research", said Professor Ludwig Kappos, from the Department of Neurology, University Hospital Basel, Switzerland, and a member of the Steering Committee of the REFLEX study. "The REFLEX study will determine the respective therapeutic benefit of two different dosage regimens of the new formulation of Rebif(R) for people at risk of developing multiple sclerosis."

The REFLEX study is a randomized, double-blind, placebo-controlled, multicenter trial. Study participants will receive either the new formulation of Rebif(R) 44 mcg three times a week (160 patients), or the new formulation of Rebif(R) 44 mcg once a week (160 patients), or placebo (160 patients) as a subcutaneous injection for a period of 24 months, unless they suffer from a second attack leading to a diagnosis of clinically definite MS. In this case, patients will be offered open label treatment with the new formulation of Rebif(R) 44 mcg three times a week. The primary endpoint of the study is time to conversion to MS, according to the McDonald criteria. Other endpoints will include assessments of MRI brain scans, clinical relapses and disability progression.

The REFLEX study will also evaluate the effect of the new formulation of Rebif(R) on cognitive function as measured by the Paced Auditory Serial Addition Test (PASAT)[1]. Cognitive dysfunction can occur early in MS and impact memory, ability to process information and learning. A sub-study will assess retinal nerve fiber thickness (a marker of axonal loss) by means of optical coherence tomography (OCT). This sub-study will be conducted in selected centers, equipped with this leading edge technology. In addition, the REFLEX study will aim at identifying genetic/genomic profiles associated with disease and treatment outcomes.

The new formulation of Rebif(R) has been developed by an innovative approach, using state-of-the-art technologies. It is under regulatory review by the European Medicines Agency, the US Food and Drug Administration and other healthcare authorities, and is not currently approved.

2006-12-29T10:29:00.000-08:00

Why Rebif: CLICK TO GO TO REBIF'S HOME PAGE
Only you and your doctor can decide if your current therapy is right for you. If it is not, you might want to think about Rebif® (interferon beta-1a). Rebif has been widely studied in several clinical studies. Two of those studies which proved Rebif's efficacy in relapsing MS are the PRISMS Study and the EVIDENCE† Study.

PRISMS Study - The PRISMS Study is the largest study of interferon beta-1a ever conducted in relapsing-remitting MS (RRMS) and proved that Rebif is an effective treatment at reducing relapses and delaying disease progression vs. placebo over 2 years and sustained over 4 years.

EVIDENCE Study - The EVIDENCE Study demonstrated the superior effectiveness of a higher, more frequent subcutaneous interferon beta-1a dosing of Rebif 44mcg tiw versus Avonex 30 mcg qw at reducing relapses at 24 and 48 weeks. These results were seen in patients through the completion of the study — average 64 weeks.

Rebif — the drug that made history

Rebif was approved by the FDA in 2002 because it met the requirements of the Orphan Drug Act for superior efficacy.

The Orphan Drug Act gives a 7-year market exclusivity to a company that develops a treatment for a rare disease, such as MS. In 1996, Avonex was granted 7-year market exclusivity for MS in the United States under the terms of the Orphan Drug Act. Exclusivity was granted through May 2003. The makers of Rebif wanted FDA approval before then, so they had to show Rebif was either safer or worked better than Avonex to overcome the exclusivity. In a head-to-head study, Rebif 44 mcg tiw proved to work better than Avonex 30 mcg qw at reducing the frequency of relapses. This was proven at 24 and 48 weeks.

The FDA granted Rebif the ONLY exception to the exclusivity rule based on efficacy.

Compared to Avonex, side effects were generally similar despite the higher, more frequent dosing of Rebif 44 mcg tiw with three exceptions. As to be expected with higher, more frequent dosing, people taking Rebif had a greater number of injection-site reactions (85% Rebif vs 33% Avonex), liver disorders (18% Rebif vs 10% Avonex), and white blood cell disorders (13.6% Rebif vs 5.3% Avonex). However, the rate of discontinuation or serious adverse events were similar for the two drugs. Flu-like symptoms were significantly higher for people taking Avonex than for people taking Rebif (45% Rebif vs. 53% Avonex).

*PRISMS Study: Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis.

†EVIDENCE: Evidence for Interferon Dose Response: European-North American Comparative Efficacy Study.

Avonex ® (interferon beta-1a) is a registered trademark of Biogen Idec® Inc.

2006-11-08T20:59:00.000-08:00

REBIF & COPAXONE: From new ideas to Nobel prizes, Israeli university research forges ahead
[PHOTO: Professors Aaron Ciechanover, 57, (right) and Avram Hershko, 67, in their lab at the Technion-Israeli Institute in Haifa.]
If the high tech and biotech industries are the engines that have been driving the Israeli economy over the past five years, it is the nation's universities that have provided the fuel: brainpower.

Behind nearly every Israeli business success story is an idea which born in a laboratory in one of the country's impressive institutions of higher learning.

Innovation at Israeli universities, of course, is nothing new. But what has rapidly improved has been the journey from university to the marketplace. Once a rough and rocky path filled with obstacles, the road to commercialization has become smoother and more efficient, thanks to the level of assistance and support provided by the universities themselves.

The past five years has seen a blossoming and expansion of what are known as technology transfer companies: businesses housed on campus that are devoted to taking the products of the university's minds, presenting them to the business world, and guaranteeing, with its proactive role, that the universities benefit financially from the ideas that they foster.

Israel's best-known technology transfer company, admired and imitated around the world, is the Weizmann Institute's Yeda Research and Development.

"In all, Weizmann scientists have been responsible for well over 1,000 registered patents, many of which have been developed commercially.

Among its licenses are two of the four drugs used in the United States and worldwide to treat multiple sclerosis - Copaxone made by Israel-based Teva Pharmaceuticals, whose annual sales top $360 million, and Rebif, made by Ares Serono of Switzerland and developed by its subsidiary Interpharm, whose sales exceed $370 million. "

2006-10-09T07:37:00.001-07:00

New Formulation Rebif for Relapsing Multiple Sclerosis Lowers Immunogenicity and Improves Tolerability

MADRID, SPAIN -- September 30, 2006 -- At 48 weeks into a 96 week phase 3b trial, a new formulation of Rebif (interferon beta-1a), researchers report that 44 mcg given subcutaneously 3 time a weeks significantly improves tolerability and reduces antibody formation compared with historical 48-week data on the currently available formulation of the drug in patients with relapsing multiple sclerosis (MS).

The data were presented here on September 28th at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

........."Rebif is already effective," said lead investigator Gavin Giovannoni, MD, consulting neurologist at the Institute of Neurology, University College in London, UK. "But here, with this new formulation, we see lower immunogenicity emerging, which is very important for relapse reduction. Notably, we also see a 3-fold lower rate of injection site reactions, and they were all mild to moderate," he added....

The new formulation has no animal or human-derived components. It is also delivered with a new auto-injector, which uses the thinnest needle in a ready-to-use syringe for use in MS treatment....

[PRESENTATION STUDY NAME: Reduced Immunogenicity With a New Formulation of Interferon-Beta-1a (Rebif): 24-Week Results of a Phase IIIb Study. Abstract P675]

2006-10-09T07:37:00.000-07:00

2006-10-09T07:32:00.000-07:00

ONE-YEAR DATA FROM PHASE III TRIAL SHOW THAT NEW FORMULATION OF REBIF® OFFERS SUBSTANTIAL IMPROVEMENT IN TOLERABILITY AND IMMUNOGENICITY PROFILES...[click for full press release]:
Madrid, Spain, September 28, 2006 - Serono (virt-x: SEO and NYSE: SRA) announced today data from an ongoing two-year (96 weeks) Phase IIIb trial show that the new formulation of Rebif® (interferon beta-1a) 44 mcg subcutaneously (sc) three times weekly (tiw) for the treatment of relapsing forms of multiple sclerosis (MS) offers substantial improvement in tolerability and reduction in antibody formation observed at one year (48 weeks), compared with historical data from patients. Historical data for the currently available formulation of Rebif® is the EVIDENCE study. These data are presented today at a satellite symposium at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Madrid, Spain.

“These results are promising news for patients with multiple sclerosis," said Prof Per Soelberg Sørensen, from the Danish MS Research Center, Copenhagen University Hospital, Rigshospitalet and an investigator of the trial.

“If approved the new formulation of Rebif® potentially represents an improvement in the treatment of patients with multiple sclerosis.”

The incidence of injection site reactions with the new formulation of Rebif® at 48 weeks was nearly three-fold less than in the EVIDENCE study (29.6% versus 83.8%). Injection site reactions are one of the reasons why some patients discontinue MS treatment. Treatment enhancements resulting in a decrease of injection site reactions are usually associated with improved compliance and adherence to treatment......

“The new formulation of Rebif® has been developed by an innovative approach, using state-of-the-art technologies, with a major focus on the molecule’s structural and functional integrity”, said Franck Latrille, Senior Executive Vice President Global Product Development at Serono. “Based on the improvements in tolerability and immunogenicity, the new formulation of Rebif® could lead to an improved benefit-to-risk profile”.
......MORE

PRESS RELEASE: Data Presented at 22nd ECTRIMS Congress in Madri

2006-09-27T23:43:00.000-07:00

ONE-YEAR DATA FROM PHASE III TRIAL SHOW THAT NEW FORMULATION OF REBIF® OFFERS SUBSTANTIAL IMPROVEMENT IN TOLERABILITY AND IMMUNOGENICITY PROFILES:
Madrid, Spain, September 28, 2006 - Serono (virt-x: SEO and NYSE: SRA) announced today data from an ongoing two-year (96 weeks) Phase IIIb trial show that the new formulation of Rebif® (interferon beta-1a) 44 mcg subcutaneously (sc) three times weekly (tiw) for the treatment of relapsing forms of multiple sclerosis (MS) offers substantial improvement in tolerability and reduction in antibody formation observed at one year (48 weeks), compared with historical data from patients. Historical data for the currently available formulation of Rebif® is the EVIDENCE study. These data are presented today at a satellite symposium at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Madrid, Spain.

“These results are promising news for patients with multiple sclerosis," said Prof Per Soelberg Sørensen, from the Danish MS Research Center, Copenhagen University Hospital, Rigshospitalet and an investigator of the trial.

“If approved the new formulation of Rebif® potentially represents an improvement in the treatment of patients with multiple sclerosis.”

The incidence of injection site reactions with the new formulation of Rebif® at 48 weeks was nearly three-fold less than in the EVIDENCE study (29.6% versus 83.8%). Injection site reactions are one of the reasons why some patients discontinue MS treatment. Treatment enhancements resulting in a decrease of injection site reactions are usually associated with improved compliance and adherence to treatment.

The primary endpoint of the study is the proportion of neutralizing antibody positive patients at the last assessment. At 48 weeks, the data showed that 13.9% of patients treated with the new formulation of Rebif® were neutralizing antibody positive. In the EVIDENCE study at 48 weeks, 24.4% of the patients were positive. Persistent neutralizing antibodies were detected in 2.5% of the patients treated with the new formulation of Rebif® at 48 weeks. In the EVIDENCE study at 48 weeks, the rate of persistent neutralizing antibodies observed was 14.3%.

“The new formulation of Rebif® has been developed by an innovative approach, using state-of-the-art technologies, with a major focus on the molecule’s structural and functional integrity”, said Franck Latrille, Senior Executive Vice President Global Product Development at Serono. “Based on the improvements in tolerability and immunogenicity, the new formulation of Rebif® could lead to an improved benefit-to-risk profile”.

The new formulation of Rebif® is the latest of many product developments from Serono to continually enhance the convenience and tolerability of Rebif®. Other enhancements have included the Rebiject II auto-injector to facilitate injections; a 29 gauge-5 bevel needle pre-filled syringe, the thinnest needle in a ready-to-use pre-filled syringe for the treatment of MS; and a titration pack designed to make starting on Rebif® therapy easier and more convenient. The new formulation of Rebif® is currently under regulatory review by the European Medicines Agency, the US Food and Drug Administration and other healthcare authorities.

The results presented today are the 48-week results from a 96-week, Phase IIIb, multicenter, single-arm, open-label study evaluating the safety and immunogenicity of the new formulation of Rebif® 44 mcg sc tiw in 260 patients with relapsing forms of MS. The primary objective of the study was to compare the antigenicity of new formulation Rebif to historical data.

About Rebif®

Rebif® (interferon beta-1a) is a disease-modifying drug used to treat relapsing forms of multiple sclerosis and is similar to the interferon beta protein produced by the human body. Interferon helps modulate the body’s immune system, fight disease and reduce inflammation.

Rebif®, which was approved in Europe in 1998 and in the US in 2002, is registered in more than 80 countries worldwide. In the United States, Rebif® is co-marketed by Serono, Inc. and Pfizer Inc. Rebif® has been proven to delay the progression of disability, reduce the frequency of relapses and reduce MRI lesion activity and area1. Rebif® is available in a 22 mcg and 44 mcg ready-to-use pre-filled syringe and a titration pack, and can be stored at room temperature for up to 30 days if a refrigerator is not available.
Most commonly reported side effects are injection site disorders, flu-like symptoms, elevation of liver enzymes and blood cell abnormalities. Patients, especially those with depression, seizure disorders, or liver problems, should discuss treatment with Rebif® with their doctors.

1 The exact relationship between MRI findings and the clinical status of patients is unknown......MORE

2006-07-10T00:24:00.000-07:00

Serono Press Release - Throughout the European Union, multiple sclerosis patients can now benefit from Rebif® as soon as their diagnosis of MS is confirmed - Serono announced today that the European Commission has approved an update of the Summary of Product Characteristics (SmPC) of Rebif (interferon beta-1a), in order to align it with current medical practice. Throughout the European Union, Rebif can now be prescribed after the diagnosis of multiple sclerosis (MS) has been confirmed based on one attack and subsequent positive magnetic resonance imaging (MRI) scans.The ‘therapeutic indication’ section of the SmPC of Rebif® now takes into account the McDonald criteria, which are the current reference criteria for the diagnosis of MS. The SmPC of Rebif® was previously based on the Poser criteria, which were in use at the time of Rebif® approval in the European Union in 1998, and Rebif® was consequently indicated for MS patients who had experienced at least two attacks. Compared with the Poser criteria, the McDonald criteria utilize MRI evidence as an alternative to a second attack, and allow the same patients to be diagnosed with more sensitivity and specificity. Current understanding of the disease supports that it is critical to initiate treatment as soon as the diagnosis of MS is established to ensure the best possible outcome for the patients.

“We are delighted with the European Commission decision,” said Roberto Gradnik, Senior Executive Vice President Europe at Serono. “MS has an initial stage when clinical manifestations are not pronounced but irreversible neurological damage is taking place. This neurological damage determines the relative risk of progression of the disease. People with MS living in Europe will be able to benefit from the proven efficacy of Rebif® as soon as MS is diagnosed, when it is needed most”.
Rebif® is proven effective on the following three key measures of treatment effectiveness: MRI lesion area and activity, relapse rates, and disability progression. The safety and efficacy of Rebif® are supported by eight-year follow-up data and 12 years of patient experience from around the world.

The European Commission decision means that the updated SmPC of Rebif® is valid immediately in all 25 member states of the European Union. In most other regions of the world, the therapeutic indication of Rebif® already takes into account the McDonald criteria.
About Rebif®....."

Back in the saddle

2006-05-30T23:20:00.000-07:00

Because the steroids she was taking to alleviate her MS would not allow her to sleep, Richens found herself one winter morning staring at the financial network on television at 4 a.m. "I thought I was going crazy," she said. Suddenly the anchorman announced that the U.S. Food and Drug Administration had approved a new drug, REBIF, which had been having dramatic results for MS sufferers in Europe.

A telephone number was provided for MS Lifelines, an information hot line, and Richens "hit redial until 8 a.m. I was their first caller."

Richens said MS Lifelines was the answer to her prayers. "They did everything for me," she said. "My insurance wouldn't cover the drug because it was so new, so they paid for it. They sent a nurse to teach me how to care for myself and take the medication. Talking to the hot line was like talking to a bartender late at night. I could let out all my secrets. I wasn't alone."

With daily injections of REBIF and a regimen of six other drugs, Richens' symptoms began to recede. She still was unable to walk without shuffling, but she knew she was getting stronger.

CLICK TO READ MORE: "Carolyn Richens feeds a flake of hay to one of her American quarter horse geldings while making the rounds in her stable in Pittsfield on Monday afternoon. Richens, a Pittsfield resident, was diagnosed with multiple sclerosis nearly 10 years ago. With the help of drugs she remains a competitive barrel racer"

Rebif's 15% thinner needle

2006-05-30T20:47:00.000-07:00

"Rebif's 29-gauge needle is the thinnest of any MS therapy.

And a thinner needle may mean more comfortable injections. In fact, in a survey of patients using the thinner needle*:

89% reported less pain
84% reported less bruising
81% reported less stinging/burning
77% reported fewer injection-site reactions"

MORE: Rebif.com (MS) Treatment Information

2006-05-30T20:10:00.000-07:00

REBIF VIDEO: "People go, oh, my gosh. M.S., you're dead. You're out of here. .... You're in a wheelchair...None of that stuff is true"
“When I got a diagnosis for M.S., I go, ‘oh, this is not stopping me. I'm not letting this stop me.’

"And I think to go around and talk about it and tell people that that's what I did and that they can do it, too, it helps people. It helps a lot of people feel better. So that makes me happy.” - And if she can do it, so can others. - “I think it's good for me to be functioning and okay and come out there and say, look, I have M.S., And if you have M.S., it's not so bad.”

For the past four or five years, Garr has been taking a powerful immunity-boosting drug called Rebif. And it seems to be working. She says her most recent M.R.I.s show no there’s been no progression of the disease.

2 VIDEOS: " Hi! I'm Heather Johnson......I'm on Rebif and I'm proud to be a Rebif Ambassador!" [Produced by the MS News Channel]

2006-05-29T23:59:00.001-07:00

Please watch my 2 videos on the left column of this page!

"I've had MS for 2 years...this is the most important advice you'll ever hear.
"This is how I give myself a painless injection."

Rebif HOME PAGE - Multiple Sclerosis (MS) Treatment Information

2006-05-29T23:59:00.000-07:00

CLICK HERE TO GO TO REBIF HOME PAGE

REBIF TIPS: From Heather

2006-05-28T21:56:00.000-07:00

"When I take the cap off the needle... i hold it UP in the air (needle facing ceiling) This helps so that no meds come out of the tip which greatly decreases site reactions! If meds come out while I'm holding the needle to the ceiling...I take the alcohol swab and clean it off."

Serono seeks OK for new form of MS drug Rebif

2006-05-28T20:25:00.000-07:00

MORE...REUTERS
Swiss biotech company Serono SA (SEO.VX: Quote, Profile, Research) said on Tuesday it had asked U.S. and European regulators to approve a new and better-tolerated formulation of its Rebif treatment for multiple sclerosis.

The company said in a statement that late-stage trials of the new formulation showed a "substantial improvement in overall tolerability," including less incidence of inflammation at the site of injections.

Serono said the trials also showed that patients taking the new formulation developed fewer antibodies -- immune system proteins that might attack the medicine -- a favorable finding that typically suggests a drug will work longer....

A MS NEWS CHANNEL PRODUCTION: " Hi! I'm Andrew Kinney...

2006-05-28T17:16:00.000-07:00

I have MS...I'm on Rebif...plus I'm proud to be a Rebif Ambassador!

Please listen to my Podcasts"

"5 YEARS WAS HOW LONG IT TOOK FOR ME TO BE DIAGNOSED WITH MS"

LISTEN NOW by clicking on the tiny black triangle below...OR

LISTEN LATER by clicking on "MP3 file" to download to your iPOD or any MP3 Player

MP3 File

Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis (INCOMIN Trial) II: analysis of MRI responses to trea

2006-05-26T19:04:00.000-07:00

CLICK HERE TO READ MORE: "Background In RRMS, clinical exacerbations are usually associated with different types of active lesions at MRI, including: hyperintense lesions on T1-weighted post-gadolinium sequences; new hyperintense lesions or enlarging old lesions on PD/T2-weighted scans; or new hypointense lesions on T1-weighted pre-Gd sequences.Objective/methods Primary outcome was the occurrence of patients with at least one active MRI lesion of the different types indicated above during treatment with 250 m g every other day (EOD) interferon beta (IFNβ)-1b or 30 μg once weekly (OW) IFNβ-1a in outpatients with RRMS (INCOMIN Trial).Results The number of patients with at least one 'active' lesion, evaluated over the two-year follow-up, was significantly (P=0.014) lower in the EOD IFNβ-1b arm (13/76, 17%) then in the OW IFNβ-1a arm (25/73, 34%). NAb frequency over two-year follow-up was 22/65 (33.8%) in the EOD IFNβ-1b arm and 4/62 (6.5%) in the OW IFNβ-1a arm, significantly greater in the EOD IFNβ-1b arm."

THINKING OF CHANGING TREATMENTS?...Sign up for the free Evaluating Your MS Therapy e-mail series

2006-05-25T17:40:00.000-07:00

The Rebif� (interferon beta-1a) Evaluating Your MS Therapy email series is a free email publication containing information you may wish to review if you are considering a change in your MS therapy. Just fill out the field below to start your brief subscription.

CLICK HERE

Why Rebif may be a good alternative to your current treatment:

2006-05-23T17:42:00.000-07:00

Changing medication may really make a difference and it is an important decision to be made with your doctor. This section will give you information as to why Rebif® (interferon beta-1a) might be the right alternative for you.
Choose an Effective Treatment >

VIDEO: HERE'S HOW REBIF WORKS

2006-05-23T16:44:00.000-07:00

CLICK HERE TO WATCH VIDEO"Find out how Rebif (interferon beta-1a) helps slow the progression of your MS."

Patient Information and/or Financial Assistance

2006-05-15T14:02:00.000-07:00

MS LifeLines  877-447-3243

www.mslifelines.com 

www.rebif.com 

www.livingwithms.com

Viragen Reports Avian Transgenic Breakthrough: OVA™ System Expresses Interferon-Beta

2006-02-20T19:10:00.000-08:00

CLICK HERE TO READ MORE: "Viragen, Inc. (AMEX: “VRA”) today announced that the Company’s scientists, along with its collaborators at the Roslin Institute and Oxford BioMedica plc, have successfully achieved expression of significant quantities of the human protein, interferon beta-1a, in the whites of eggs laid by transgenic hens using the OVA™ System (Avian Transgenic Biomanufacturing). Interferon-beta is a key component of the human immune system and is the active ingredient in several leading multiple sclerosis (MS) therapies. These results are the first in a series of anticipated milestones demonstrating “Proof-of-Principle” with an avian-expressed version of beta-interferon, and it is expected that the OVA™ System will be capable of cost-effectively expressing many types of therapeutic proteins.

Viragen and Roslin are conducting avian expression studies on various protein candidates including interferon beta-1a, which is currently marketed under two competing brand names for the treatment of MS. These MS products are Avonex®*, marketed by Biogen Idec, and Rebif®**, marketed by Serono, with combined annual global sales over $2.5 billion.

The Project’s Scientific Leader, Dr. Helen Sang of Scotland’s Roslin Institute, commented, “We are extremely pleased to report this key advance in our program to develop a preferred platform for the production of selected biopharmaceutical proteins, having now successfully developed transgenic hens that are synthesizing significant quantities of interferon-beta as a component of their egg white. This is the second protein candidate with which we have achieved promising results, as we previously reported expression and recovery of a functional humanized antibody. As we fully characterize the interferon-beta that is recovered, both biochemically and by functional tests, we expect such results will confirm our progress.”

“This is a truly remarkable achievement for our team in Scotland and represents a major event towards our goal to definitively position the OVA™ System as a revolutionary transgenic bio-manufacturing alternative,” stated Dr. Karen Jervis, Vice President and Managing Director of Viragen (Scotland) Ltd. “We will continue to collect eggs from these hens and subsequent generations to confirm quality and quantity of the protein. In addition, we will be analyzing the carbohydrate profile of the product, which may represent another key advantage to OVA™-expressed proteins. Certain biotech drugs require post-translational modifications in order that the drug retains its full efficacy and is well tolerated when used as a human therapeutic. Although we must confirm the nature of the modifications conferred by the OVA™ System, we are hopeful that avian transgenic production may be able to retain these beneficial modifications, which may in turn translate to a lower cost of goods and a more economical process.”

"Hope for young MS victims"

2006-01-20T17:56:00.000-08:00

Four doctors examined Melissa Harris before she got the correct diagnosis for her double vision: pediatric multiple sclerosis.
That was two years ago. After many visits to the University at Buffalo's Jacobs Neurological Institute, in Buffalo General Hospital, and treatment that included chemotherapy and now a disease-modifying drug called Rebif, the Fredonia 15-year-old is holding her own.

My balance is a little off, but not by much," she said....When Melissa was diagnosed at 13, her parents, Linda and Scott Harris, were stunned. But since the Fredonia Central High School sophomore began injecting herself with Rebif, one of a group of drugs called beta-interferons, her symptoms have not worsened. "She's doing wonderfully," her mother said. "She's a trouper."
READ MORE

Immune Response to Influenza Vaccine is Maintained in MS Patients Treated With Rebif (interferon beta-1a)

2005-12-13T20:49:00.000-08:00

"Data presented today at the XVIIIth World Congress of Neurology in Sydney, Australia, show that treatment with Rebif in patients with multiple sclerosis (MS) does not alter the immune response to influenza vaccination."MORE:

Flu vaccine's efficacy not impaired by Rebif

2005-11-19T20:18:00.002-08:00

IMMUNE RESPONSE TO INFLUENZA VACCINE IS MAINTAINED IN MS PATIENTS TREATED WITH REBIF

Data presented today at the XVIII th World Congress of Neurology in Sydney, Australia, show that treatment with Rebif in patients with multiple sclerosis (MS) does not alter the immune response to influenza vaccination.

Immune response to influenza vaccine was prospectively assessed in an open-label study over a four-week period in a total of 163 patients with MS. One group of MS patients (n=86) received Rebif (interferon beta-1a) 44 mcg subcutaneously three times weekly for at least six months before administration of the flu vaccine and continued their Rebif treatment after the vaccination. The control group of MS patients (n=77) did not receive interferon treatment within six months prior to study entry and during the study. Patients of both groups received a single dose of the same influenza vaccine. The data from the two groups were similar on the primary endpoint, defined by the proportion of patients achieving a hemagglutination inhibition (HI) titer %u226540 four weeks after vaccination, which indicates the ability of patients to mount a positive vaccine response. More than 90% of the patients in both groups (93% in the Rebif-treated patients group and 91% in the group of patients receiving no interferon treatment) were able to mount an appropriate immune response.

No new safety concerns regarding the treatment of MS patients with Rebif were identified. The proportion of patients experiencing a vaccine-related adverse event was similar for both the Rebif-treated group and the control group.

"These results demonstrate that treatment with Rebif does not alter the immune response to influenza vaccination, and that this vaccination can be performed safely in MS patients who are treated with Rebif," said Dr. Paul Lammers, Chief Medical Officer of Serono, Inc. "This news is important for patients treated with Rebif as vaccination may provide medical benefits to people with MS by preventing an influenza virus infection, and also by possibly avoiding MS exacerbations or worsening of neurologic symptoms due to concurrent viral infection."

The importance of MS patients avoiding viral infections was previously outlined by the Immunization Panel of the MS Council for Clinical Practice Guidelines. The meta-analysis performed by the Panel demonstrated that MS subjects were at increased risk of MS exacerbation during concurrent viral infections.
Serono Group -

Media - Archives 2005

Biogen Idec CEO says not interested in Serono(REBIF)

2005-11-12T23:38:00.000-08:00

MORE: Reuters.com: "The CEO of the U.S. maker of multiple sclerosis treatments said that he saw no sense in a deal...because of their important MS products there would be huge competition issues in Europe and the U.S.'"

REBIF: Serono reports it is looking for a buyer

2005-11-08T20:58:00.000-08:00

Spotlight on Subcutaneous Recombinant Interferon-beta-1a Rebif in Relapsing-Remitting Multiple Sclerosis

2005-11-03T06:55:00.000-08:00

Entrez PubMed
: "A significant efficacy advantage for subcutaneous interferon-beta-1a three times weekly over intramuscular interferon-beta-1a 30microg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-beta-1a 44microg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat relapsing-remitting multiple sclerosis"

Nephrotic syndrome in a multiple sclerosis patient treated with interferon beta 1a

2005-11-03T06:32:00.000-08:00

MORE-Entrez PubMed

SERONO'S (REBIF) THIRD QUARTER 2005 ADJUSTED EPS INCREASED BY 37.6%

2005-10-30T08:43:00.000-08:00

Serono Inc. - MORE

News - Rebif (Interferon Beta-1a) More Effective In Reducing Frequency of Relapses in Relapsing Forms of Multiple Sclerosis

2005-10-30T08:41:00.000-08:00

"Serono, S.A. and Pfizer Inc today announced that the final 63-week findings from the Rebif® (interferon beta-1a) vs. Avonex® (interferon beta-1a) EVIDENCE head-to-head study continue to show that Rebif is significantly more effective in reducing frequency of relapses and MRI activity as compared to Avonex.(1) These newly released data further support the benefit of increased dose and frequency of interferon administration in the treatment of relapsing forms of multiple sclerosis (MS).

The findings are consistent with data comparing Rebif and Avonex at 24 and 48 weeks.(2) The 63-week results will be presented by Hillel Panitch, M.D., a University of Vermont College of Medicine clinical researcher and member of the EVIDENCE Study Group, at the annual meeting of the Consortium of Multiple Sclerosis Centers held this week in San Diego, CA.

"This additional data comparing Rebif and Avonex provides further information for physicians and people with relapsing forms of MS in choosing an interferon treatment," said Dr. Panitch. "It adds to the weight of scientific data supporting the clinical superiority of Rebif over Avonex at reducing frequency of relapses as observed at 24 and 48 weeks," he added.

The EVIDENCE study, which involved 677 patients with relapsing remitting MS, was designed to compare the proportion of MS patients treated with either Rebif (44 mcg three times weekly, subcutaneously) or Avonex (30 mcg once weekly, intramuscularly) who were relapse-free after 24 weeks (primary endpoint) and 48 weeks. Approximately 90% of patients continued in the study for an average of 63 weeks.

EVIDENCE Study data over 63 weeks consistent with previous findings At 63 weeks, 56% of Rebif patients versus 48% of Avonex patients remained relapse free (p=0.023). Rebif patients had a 17% relative increase in the risk to remain relapse free as compared to Avonex patients, and is consistent with previously published EVIDENCE Study data. Other relapse measures such as overall relapse rate, time to first relapse, and steroid use for relapses were also significantly better in Rebif than Avonex patients.

Regarding MRI activity, mean T2 active lesion count was 0.9 for Rebif treated patients and 1.4 for Avonex treated patients (p<0.001); mean proportion of active scans per patient was 27% for Rebif treated patients and 44% for Avonex treated patients (p<0.001); and the proportion of patients with no active scans was 58% for Rebif treated patients and 38% for Avonex treated patients (p<0.001). The exact relationship between MRI findings and clinical outcomes for patients is unknown.

No new safety concerns were noted with comparable numbers of treatment discontinuations in both groups. Adverse events reported more frequently with Rebif were injection site reactions, asymptomatic liver function test changes and white blood cell abnormalities. Flu-like symptoms were reported in significantly more patients treated with Avonex than with Rebif (p=0.031).
"MORE: docguide.com

TERI GAR - MS LifeLines AMBASSADOR

2005-10-23T16:52:00.000-07:00

Well, it's true what you've heard: I do have a slight case of MS. I like to say it that way because it keeps things in perspective. I also have a life and believe me, that's a lot more important! This MS thing is just along for the ride.

My dream is to change the view so many people have about MS: that it equals a ruined life. I'm here to tell you that it doesn't and that life goes on and it's pretty damn good. Although I did notice my work opportunities thinning out a bit. Was it my acting ability or the MS rumors? In Hollywood it's amazing how quickly people jump on the negative bandwagon — "Split ends? She's OUT."

MS affects each of us so differently. That's why I think it's important for everyone with MS to share their stories. We can help each other — you know, a little comparison shopping.

The first thing I felt was a little beep, beep on my foot. It was 1983 and I was living in New York City, jogging every day in Central Park. I started tripping but didn't think anything of it. Then I felt a tingling in my arm that gradually increased. When it became a sharp, stabbing pain I decided to see a doctor.

He said, "You have a bulging disc and we need to operate on Thursday," which seemed a little crazy since he hadn't taken so much as an X-ray. So I asked for a second opinion and was told by the second doctor that I had a degenerative nerve disease and he needed to stretch my spine. He put me in the hospital for 10 days, gave me 18 tons of Valium, and sent me home with ropes, pulleys, and sandbags — some kind of medieval torture thing I was supposed to strap over the doorway and hook up to my neck for 15 minutes twice a day. Maybe MRI will seem archaic someday, but it beats the hell out of ropes and pulleys.

All I wanted to do was go back to work. So when I started to feel better I said, "Oh good, it's gone." I assumed it was like a cold sore: when it's gone, it's gone. For a long time I was physically fine. Ten years later I started tripping again.

In 1999, I saw a doctor at UCLA who put me in a hot tub — only in California, right? When I got out I was tired and weak. He said, "This looks like MS." I asked, "So what can we do about it?" He said, "Right now, nothing." I said, "OK, so it's kinda like expecting an earthquake." What was the point of worrying about it if there was nothing I could do? So I started my first MS therapy — denial, one of the earliest treatments for MS, and in my opinion, one of the best.

Later when people asked why I was limping, I'd say "skiing accident," "pinched nerve" — anything but "MS." Because I was really scared of what it might do to my life, my career. Here's another big reason: I didn't want to be a victim. If you are an athlete or a dancer, as I was, you are taught not to complain. If you fall down you get right back up again! It's a little something I got from my mom.

My mother was a dancer and my biggest role model. My dad passed away when I was 11. Here she was with no husband, no income, and three kids to take care of. We moved to a small house and she worked in a knit shop and took in sewing, eventually getting a studio job in wardrobe. When my brother needed a room to study in she bought a used trailer. On the back was a sign that read "Kwitcher Bitchin." I said "Mom, we should take that off" and she said, "No, we're leaving that on so you always remember to kwitcher bitchin." She put three kids through school: a doctor, a boat builder, and me. Whenever I feel like having my own personal pity party, I think of the sign on the back of that trailer.

I finally got serious and tried a real medicine for a change. It didn't work as well as I had hoped, and the side effects were a problem for me, but you do what you have to do. I also realized that MS wasn't stopping me from getting work. I mean, what's the difference between being handicapped and being a woman over 50 in Hollywood? I'm over 50 and I have relapsing MS. For the MS, I now take a medicine called Rebif® (interferon beta-1a). For the over 50, I'm working on a youth serum like everyone else.

One thing that keeps me going is my nine-year-old daughter, Molly. She is hell on wheels. I tried to make her take ballet but she wants the chess club and baseball. Kids today. People ask me how Molly deals with my MS. She really doesn't have any preconceived notions about it. As far as she's concerned, you can have a cold, or you can have MS. And I think that's good.

I'm also lucky enough to have an ex-husband, "ex-" being the key word there. Unfortunately, MS doesn't stop you from having bad relationships. I can still pick the handsome dysfunctional Irish guy out of a roomful of saints. But he does take her camping, skiing — the things I can't do. Whereas I'm finally learning state capitals and working on 4th grade math. I've learned a few other things that have helped me along the way, and I hope they help you:

Be positive. The right attitude really helps me cope, and a sense of humor is critical. My neurologist recently told me that if we can just hang in for two or three more years, there is going to be a lot of great help for us. Of course my ex-husband made the same promise, but I believe my neurologist.

Find out about MS medicines. It sounds weird to say but this is a good time to get MS because of the choices available to treat it. As I mentioned, I am taking Rebif, which seems to be working for me. I experience minimal side effects, mostly consisting of a little redness where I inject.

Stay active. Keeping fit is a challenge for everybody as they get older. For people with MS, I think it's got to be slow and strong. So for me, Pilates is great.

Make adjustments. In the old days I would do 50 things in a day and be fine. Of course when I say 50, I actually mean eight. Today I accept that I can do maybe three things in a day, but I do them better because I've adjusted to my abilities.MORE

VIDEO: HOW REBIF WORKS

2005-10-23T16:36:00.000-07:00

Find out how Rebif (interferon beta-1a)
helps slow the progression of your MS.

CLICK HERE THEN GO TO TOP RIGHT CORNER AND CLICK ON VIDEO

Frequently Asked Questions: Rebif

2005-10-23T16:33:00.000-07:00

CLICK TO READ

2005-10-23T16:28:00.000-07:00

It can be hard living with MS, especially when facing frequent relapses or when you are experiencing increased disability despite being on treatment. At times like these it's important to talk to your doctor. It may be time to consider another therapy. One thing you'll want to know is that Rebif® (interferon beta-1a) has been proven effective against MS in three important ways.

The PRISMS* Study, the largest study of interferon beta-1a ever conducted in relapsing-remitting MS, proved that Rebif 44 mcg three times per week effectively reduced relapses and delayed progression of disability versus placebo over a two-year period.

The EVIDENCE† Study, a completed head-to-head comparative study of MS treatments, showed that people taking the higher, more frequent dosing of Rebif — 44 mcg three times a week — were more likely to remain relapse-free than people treated with Avonex® (interferon beta-1a) 30 mcg once a week. This was proven at 24 and 48 weeks, and the results were maintained through the completion of the study (average 64 weeks).

People in the PRISMS* Study underwent MRI†† scans twice a year to assess the effect of treatment. In this study, Rebif 44 mcg three times per week significantly reduced the number of new and active T2 lesions versus placebo over a two-year period.

Moreover, the EVIDENCE† Study showed that people taking Rebif 44 mcg three times per week had a significant reduction in MRI activity versus those treated with Avonex 30 mcg once a week — at 24 weeks, 48 weeks, and up to an average of 64 weeks.

††The exact relationship between MRI findings and the clinical status of patients is unknown.

In the PRISMS* Study, Rebif 44 mcg three times per week was proven to significantly delay the progression of disability versus placebo over a two-year period.MORE

Rebif May Be Right For You

2005-10-23T16:20:00.000-07:00

You can pick the days that work best with your schedule. Rebif injections should be taken on the same three days a week. Injections should be at least 48 hours apart. Many people choose to take their injections on Monday, Wednesday, and Friday so that they have injection free weekends. After you decide which three days work best for your lifestyle, stick with those to help make your injections part of your weekly routine. If you accidentally take more than your prescribed dose, call your doctor right away.

Rebif is given by subcutaneous (under the skin) injection, as opposed to intramuscular (into the muscle) injection. With Rebif, you only have to put the needle right beneath your skin, and Rebif now uses a 29-gauge needle — the thinnest of any MS therapy.

Rebif comes ready to use, in syringes that already contain the medicine and do not require needle assembly, so you don't have to worry about mixing any solutions before injection. Monthly supplies of Rebif syringes are provided.

MORE

Take the MS Assessment

2005-10-23T16:15:00.000-07:00

Learning you have multiple sclerosis is not something anyone is ever ready for. With this diagnosis naturally comes uncertainty about what the future will bring. We're here to help, because you should know that having MS does not necessarily mean giving up all your life plans. Take this assessment to learn more about MS and possible treatment options available to you. MORE

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2005-10-23T16:09:00.000-07:00

"I GAVE MYSELF MY 500TH SHOT THIS MONTH....HERE'S A QUICK LESSON FOR YOU"...Andrew Kinney

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2005-10-21T21:54:00.000-07:00

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Effects of dose titration on tolerability and efficacy of interferon beta-1b in people with multiple sclerosis

2005-10-21T17:47:00.000-07:00

Effects of dose titrationMultiple sclerosis (MS) treatment with interferon beta is associated with well-known, easily managed adverse events, including influenza-like symptoms and injection-site reactions that decline over time. Initial dose titration has been shown to be one way of limiting these adverse events. Hence, a placebo-controlled, multicentre study of 98 patients was set up to explore whether a slower, four-stage, 4-week titration to a final dose of 250 microg subcutaneous interferon beta-1b might improve tolerability over a more rapid two-stage, 2-week titration in patients with relapsing-remitting MS. Frequency of adverse events was found to be similar between the two regimens: notably, no difference in the incidence of injection-site reactions, with a trend towards fewer influenza-like symptoms in the slow-titration group. Relative to placebo, significantly fewer patients receiving interferon beta-1b relapsed. This was more pronounced in the rapid-titration group than in the slow-titration group, showing that rapid and significant improvements in relapse rates were achieved within 90 days of starting interferon beta-1b. Although a rapid-titration regimen results in a quicker onset of clinical benefit, slow titration showed a non-significant trend towards reduced influenza-like symptoms.

Not all Interferon-beta Treatments are Created Equal in Developing Neutralizing Antibodies

2005-10-21T17:34:00.000-07:00

Neutralizing Antibodies can significantly decrease the effectiveness of IFN-b in the treatment of MS

Three studies published in Neurology which included more than 1200 patients, confirm that the three interferon preparations used to treat relapsing-remitting multiple sclerosis (MS) vary in their rate of production of neutralizing antibodies (NAbs).

Further, there is agreement that NAbs reduce or eliminate the biologic activity and clinical efficacy of the interferon-beta (IFN-b) therapies.

Once-weekly Avonex® (interferon beta-1a IM) was shown to be significantly less likely to induce the development of NAbs than the other two available interferon therapies (Rebif® and Betaseron®). Since NAbs reduce or eliminate the clinical benefits of the interferons, these studies highlight a concern for MS patients, neurologists and those who pay for these medications.

"MS is a chronic disease, and patients need to have the confidence that their therapy will retain its efficacy throughout the course of treatment, which is often for many years," commented Dr. Stanley Hashimoto, neurologist and former medical director of the University of British Columbia MS Clinic, Vancouver, Clinical Director of the UBC MS Clinic, Vancouver, British Columbia. "These studies confirm that in MS, high titre and persistent NAbs are very important in eliminating the efficacy of the therapeutic agent. It is important that we have available a less immunogenic option such as Avonex®."

While each of the studies showed slightly different rates of NAbs, Avonex® (interferon beta-1a IM) consistently demonstrated the lowest rates as compared to the other IFNb therapies. For example, in the first study the Danish Multiple Sclerosis Study group (Neurology 2005;65:33-39) concluded, "Unlike previous findings reported in the literature we did not find any difference in the proportion of patients treated with [Betaseron®] and [Rebif®] who became NAb-positive, but could confirm that Avonex® is much less immunogenic."

In the second study, Kappos and associates (Neurology 2005;65:40-47) analyzed 395 patients over four years in a controlled trial, and clearly demonstrated the loss of efficacy in terms of relapse rate reduction and disability progression over a significant number of years. It can be assumed from this research, that persisting NAbs beyond the four years will continue to suppress the therapeutic activity of the interferons. This was also echoed by Drs. Giovannoni and Goodman in their Editorial (Neurology 2005;65:6-8).

The third study, authored by Dr. Gordon Francis et al. (Neurology 2005;65:48-55), concluded that, "Neutralizing antibody development in IFN-b-treated patients is correlated with reduced efficacy and is a potential cause for renewed (MS) disease activity."

"Many patients being treated for MS are not getting the efficacy they deserve because of the neutralizing effect of NAbs," said Dr. Hashimoto "This is not to mention the fact that our healthcare system is paying for these drugs without realizing the potential negative effects of neutralizing antibodies."

The Danish Multiple Sclerosis study group agreed that the presence of NAbs decrease or eliminate efficacy of the interferons. They recommended that to avoid these negative consequences, all patients on the therapies should be tested at six-month intervals for two years when it becomes less likely the new positivity will develop. Routine testing will assure patients that they are self-injecting their medication and getting benefit from it.

With recent concerns about existing and future MS treatments, patients and physicians are reassessing currently available therapies, like the interferons. As a result, it is more important than ever to re-evaluate which therapy will provide efficacy over the long-term, including minimizing the formation of NAbs

docguide.com

trial of the tolerability of interferon beta-1a (Rebif) administered by autoinjection or manual injection in MS

2005-10-21T15:43:00.000-07:00

The decreased incidence of ISRs with the autoinjector compared to manual injection seen in this short-term study, coupled with ease of use of the autoinjector, suggest that it could improve compliance, and therefore therapeutic outcomes in some patients.MORE...Entrez PubMed

STUDY...Predictors of long-term clinical response to interferon beta therapy in relapsing multiple sclerosis.

2005-09-11T16:35:00.000-07:00

OBJECTIVES: The aim of this study was to identify clinical, magnetic resonance imaging (MRI) and biological markers predictive of long-term clinical response to interferon beta (IFN beta) therapy in patients with relapsing-remitting multiple sclerosis (RRMS).METHODS: Sixty-eight patients treated with IFN beta were followed over a 6-year period. Relapse rate and disability progression were evaluated throughout the study. We considered suboptimal clinical response to be either the presence of sustained disability progression, or more than two relapses. Baseline and 12-month demographic, clinical and MRI findings, as well as the development of neutralizing antibodies (NAbs) against IFN beta during the first year of therapy were analyzed as predictors of long-term clinical outcome..CONCLUSIONS: Variables assessable within the first year of treatment significantly influence relapse rate and disability progression in patients with RRMS treated with IFN beta. These findings may help clinicians to make decisions regarding therapy regimen over time, and highlight the need for a prognostic algorithm.Entrez PubMed

Rebif is manufactured from one of the naturally-occurring interferons.

2005-08-28T01:19:00.000-07:00

It is made of the same amino acids as interferon beta, found in the human body. ...Click to read entire article...MS NeighborhoodStudies have demonstrated that groups receiving the medication demonstrated a lower relapse rate, prolonged time to first relapse, a higher proportion of relapse-free patients, a lower number of active lesions on MRI, and delay in progression of disability, when compared to the placebo group.

Rebif is currently available in a 44 microgram (mcg) dose in pre-filled syringes ready for subcutaneous injection.

Rebif should be stored in the refrigerator. Storage at room temperature without exposure to heat or light is permissible for up to 30 days, but the medication should not be allowed to freeze.

Flu-like symptoms are a fairly common side effect during the initial weeks of treatment, so it is recommended that the injection be given at bedtime. Your doctor may prescribe medications to decrease these side effects.

Docs Evaluate Effects of Long-Term MS Therapy of the four different interferon-beta preparations

2005-08-16T16:54:00.000-07:00

Click to read... The study, which is still ongoing, is labeled Quality Assessment in MS Therapy, or QUASIMS. "The goal of this study was to compare the efficacy of interferon-beta products in relapsing MS in different clinical settings throughout the world," Limmoth and his fellow investigators wrote. Patients were included in the study if they had been taking one of four interferon betas uninterrupted for at least two years. That included 30 micrograms (mcg) of Avonex (interferon beta-1a) once per week, 250 mcg of Betaseron (interferon beta-1b) once every other day, or two different doses of Rebif (interferon beta-1a): 22 mcg or 44 mcg three times per week.

"Efficacy was similar among patients treated with the four different interferon-beta preparations in different countries," the researchers wrote. "Switching between different interferon preparations did not appear to provide additional benefits."

MS Neighborhood : Rebif

2005-08-07T14:11:00.000-07:00

LINKRebif is manufactured from one of the naturally-occurring interferons.

It is made of the same amino acidsas interferon beta, found in the human body.

Studies have demonstrated that groups receiving the medication demonstrated a lower relapse rate, prolonged time to first relapse, a higher proportion of relapse-free patients, a lower number of active lesions on MRI, and delay in progression of disability, when compared to the placebo group.

Rebif is currently available in a 44mcg dose in pre-filled syringes ready for subcutaneous injection.

Rebif should be stored in the refrigerator. Storage at room temperature without exposure to heat or light is permissible for up to 30 days, but the medication should not be allowed to freeze.vmvmds

Flu-like symptoms are a fairly common side effect during the initial weeks of treatment, so it is recommended that the injection be given at bedtime. Your doctor may prescribe medications to decrease these side effects.

Precautions While Using Rebif

2005-08-03T22:40:00.001-07:00

LINKRebif should not be used during pregnancy or breast-feeding, or by any woman who is trying to become pregnant.

Women taking Rebif should use birth control measures at all times.

If you become pregnant while using Rebif, stop the treatment and contact your physician.

There was no increase in depression reported by people receiving Rebif in the clinical trial.

However, some patients treated with interferons, including Rebif, have become seriously depressed, and depression and suicidal thoughts are known to occur with some frequency in MS.

It is recommended that individuals with a history of severe depressive disorder be closely monitored while taking Rebif.

Anyone who experiences significant feelings of sadness or helplessness, or feels like hurting him- or herself or others, should consult with family or friends and their physician as soon as possible.

Rebif can affect liver function. Your physician may require regular blood tests to assess liver function.

If you notice that your skin or the whites of your eyes become yellow, or if you are bruising more easily than usual, contact your physician.

A post-marketing case of liver failure has been reported in a person taking Rebif along with another medication that was potentially toxic to the liver.

Because of the potential of Rebif to affect the levels of red and white blood cells and platelets in a person's system, blood tests are recommended at regular intervals.

Thyroid function tests are recommended every 6 months in patients with a history of thyroid dysfunction.

Serono

2005-07-26T22:50:00.000-07:00

linkSerono is the North American affiliate of Serono International SA. With nine recombinant molecules approved or under development, Serono International today ranks among the world’s leading biotechnology companies. Serono is the developer of Rebif (Interferon beta-1a)

Serono is committed to bringing hope to people suffering from multiple sclerosis.

Rebif® is the leading treatment for Relapsing MS outside the US, and is the fastest growing MS treatment in the US.

Several studies support the concept of maximal benefit with higher and more frequent doses of beta-interferon. With respect to interferon beta-1a administered subcutaneously, Rebif® 44 mcg, three times per week, has shown to achieve maximum treatment effect in terms of disease progression and reducing the frequency and severity of relapses

Combining mitoxantrone and beta interferon for MS

2005-07-08T18:00:00.000-07:00

Multiple Sclerosis Society of London Website - linkMitoxantrone is a potent immunosuppressant used in the treatment of some forms of cancer. It is licensed in the US for the treatment of worsening relapsing remitting MS and relapsing progressive MS. This study investigated the effectiveness of mitoxantrone as a "rescue therapy" for people taking beta interferon who continued to experience disabling relapses or significant disability progression.

Ten people who experienced more than three relapses a month and had rapid disability progression took part in the study. Neurological assessments, MRI scans and blood tests, both to monitor ongoing inflammation, were completed initially, every three months and within three days of a relapse. After six months receiving just beta interferon participants received three infusions of mitoxantrone into the vein, in combination with steroids, shown to shorten the recovery time after a relapse, once monthly. After an additional six months of just beta interferon therapy people who did not show a benefit from the first combination therapy again received intravenous infusions of mitoxantrone, in addition to beta interferon therapy, at the rate of once every three months. All participants were monitored for the following 15-18 months.

During the first three months of mitoxantrone treatment none of the participants experienced any relapses and disability levels stabilised. The amount of inflammation present also significantly decreased compared to levels present during beta interferon therapy alone. During the following six months of just beta interferon treatment the relapse rate remained significantly reduced and inflammation levels remained low. Disability levels for seven of the 10 participants remained stable after the initial mitoxantrone treatment. The remaining three participants received additional mitoxantrone, as described. During further mitoxantrone treatment these participants experienced no new relapses and their disability stabilised. Overall, mitoxantrone was well tolerated with a low number of adverse events reported.

In conclusion, mitoxantrone administered concurrently with beta interferon was effective in significantly reducing both the relapse rate and levels of inflammation in people with MS. It also effectively stabilised disability progression in people with rapidly progressive disease. Positive effects were still detectable after 15 months. The authors highlight that further studies of agents for rapidly progressing MS are warranted.

Cytoxan plus interferon beta as rescue therapy could be used to treat relapsing-remitting multiple sclerosis patients

2005-07-07T18:07:00.000-07:00

LINK PubMed
"These data showed that the combination of CTX plus IFN beta halted the progression of disease in active and deteriorating MS patients suggesting the necessity of RCTs to test the efficacy of this combination therapy in active RRMS patients or in patients who experienced treatment failure in response to disease modifying drugs (DMDs)."

Immune response to immunotherapy: the role of neutralising antibodies to interferon beta in the treatment of multiple sclerosis

2005-07-07T18:04:00.000-07:00

The Lancet Neurology...LINK TO ARTICLEInterferon beta was the first therapy to be approved for the treatment of relapsing-remitting multiple sclerosis (MS) more than 10 years ago. Interferon beta reduces relapse rates and disease burden and activity, and it may have beneficial effects on the progression of long-term disease disability. The occurrence of neutralising interferon-beta antibodies has been postulated as a possible cause of the failure of interferon beta in some patients with MS. Here we discuss the basic mechanisms that may account for the generation of an interferon-beta antibody response and its biological implications. We review the evidence for neutralising antibodies as a consequence of interferon-beta treatment, and discuss the implications for the treatment of MS. Strategies to assess and manage the long-term impact of neutralising antibodies will be outlined.