Sixteen-Year Follow-up Study

[Dunmann]

First Avonex, then Rebif now Betaseron... next we need some "new" info on Copaxone.


Sixteen-Year Follow-up Study Reinforces Betaseron(R) Long-Term Efficacy, Safety and Tolerability in Multiple Sclerosis
Efficacy in relapse rate reduction beyond five years shown for the first time

Berlex announced today that Betaseron® (interferon beta 1b) remained consistently safe, effective and well tolerated over the long term, according to results of the Betaseron 16-Year Long-Term Follow-up (16-Year LTF) Study presented at the 58th Annual Meeting of the American Academy of Neurology. This is the longest follow-up study for any disease modifying therapy in multiple sclerosis (MS).

Patients with relapsing forms of MS taking Betaseron (known as Betaferon® outside the US) had a sustained reduction in the annual rate of relapses of up to 40 percent over 16 years.

The data also showed that patients remaining on long-term Betaseron treatment had a slower disease progression compared to patients who did not. Among the patients who reached EDSS(1) level 6.0 (e.g., needing a cane for walking), those on long-term Betaseron treatment reached EDSS 6.0 after a median time of 13 years compared to seven years for patients on short-term treatment. Long-term treatment was defined as use of Betaseron for more than 80 percent of the time since the start of the pivotal trial (approx. 12 years or longer), while short-term treatment was defined as use for less than 10 percent of the time (approx. 1.6 years or less). The impact of long-term treatment on disease progression is being studied further using historical control groups.

"This study has comprehensively re-evaluated patients after 16 years," said Professor George Ebers, lead investigator of the study, Department of Clinical Neurology, Radcliffe Infirmary, University of Oxford. "The evidence for relapse rate reduction, combined with further support for long-term safety of Betaseron, is convincing. More studies are being done to further analyze the impact of treatment on disease progression."

The long-term use of Betaseron over 16 years revealed no new or unexpected adverse events. Betaseron was well accepted by patients in this long-term study. The median treatment duration with Betaseron of the analyzed trial participants was almost 10 years, while the longest duration on therapy is 17.1 years.

"The 16-year LTF is ground-breaking in that it is the longest follow-up study of patients on disease modifying MS therapy," said Richard Neiman, MD, Vice President, Head of Medical Affairs at Berlex. "These results show that first-line and long-term use of Betaseron for relapsing MS patients is safe, effective and well-tolerated. These data are very reassuring given the chronic nature of relapsing forms of MS, and the need for long-term therapy."

Sixteen Years of Betaseron Use in Patients with MS

The 16-Year LTF Study provides clinical assessment of patients who first enrolled in the Betaseron pivotal trial between 1988 and 1990. Of the original 372 patients involved in the pivotal trial, 328 (88.2 percent) have been identified. It is a multicenter, open-label, observational study designed to evaluate the impact of Betaseron treatment on long-term outcomes in patients with relapsing forms of MS. The study constitutes the longest follow up for any disease-modifying therapy in MS.

The results support a previously reported trend, in that there was a lower number of deaths in patients that were initially treated with Betaseron 250 mcg during the pivotal trial. This trend needs to be further evaluated.

The Betaseron pivotal trial was the first large, randomized, placebo- controlled study of any therapy in MS. This groundbreaking study was conducted in North America and led to the approval of Betaseron, the first disease-modifying agent for MS, in 1993. Patients were randomly assigned to one of three study arms, Betaseron® 50 mcg(2), Betaseron 250 mcg or placebo, with a median duration of observation of 45 months. Analysis after two years demonstrated that significantly more patients receiving Betaseron were relapse-free, that those relapses that occurred were less frequent and that hospitalizations for MS were cut nearly in half. These results were confirmed at five years.

About Betaseron

Betaseron® is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. The most commonly reported adverse reactions are lymphopenia, injection site reaction, asthenia, flu-like symptom complex, headache and pain. Betaseron should be used with caution in patients with depression. Injection site necrosis has been reported in 5 percent of patients in controlled trials. Patients should be advised of the importance of rotating injection sites. Female patients should be warned about the potential risk to pregnancy. Cases of anaphylaxis have been reported rarely. Please see full Prescribing Information for more information.

About Berlex

Berlex is committed to addressing unmet medical needs through research and development in the areas of oncology, gastroenterology, women's health, diagnostics and neurology. Berlex also markets diagnostic imaging agents, innovative treatments in the areas of female health care and oncology, as well as specialized therapeutics for life-threatening and disabling diseases of the central nervous system and cardiovascular system. Berlex has business operations in New Jersey, California and Washington. For more information, please visit http://www.berlex.com.

Certain statements in this press release that are neither reported financial results nor other historical information are forward-looking statements, including but not limited to, statements that are predictions of or indicate future events, trends, plans or objectives. Undue reliance should not be placed on such statements because, by their nature, they are subject to known and unknown risks and uncertainties and can be affected by other factors that could cause actual results and Berlex's plans and objectives to differ materially from those expressed or implied in the forward-looking statements. Berlex, Inc. undertakes no obligation to update publicly or revise any of these forward-looking statements, whether to reflect new information or future events or circumstances or otherwise.

(1) EDSS or Expanded Disability Status Scale is a standard method of evaluating a person's level of impairment due to MS. EDSS level of 6.0 is defined as being able to walk, but needing a cane, crutch or brace for assistance.

(2) The Betaseron 50 mcg dose was a study dose only. The FDA approved and marketed dose is Betaseron 250 mcg.

Source: Berlex

[LisaBee]

Dunman,

I have a question about this report. They give the total number of patients located for the followup at 88.2 percent, which is pretty good followup, only 12 percent lost to followup (I hope they're not dead, but there are less serious reasons to lose track of people).

The numbers I didn't see, though, was the number of patients in the long-term therapy group (12 years or more) versus the short term therapy group (defined as those taking it for 1.6 years or less). This means there is also a middle group (1.6 years to 12 years of treatment) that they don't talk about. That is a potential big gap of subjects. The short term people are people who, probably by a large percentage, couldn't tolerate the drug, so they wouldn't be expected to be much different than a historical control (although comparison to a historical control would be interesting). The people falling into a the middle group are people who may have developed an intolerance or kept progressing, so they stopped the drug. The people took the drug for 12 years or more must have good tolerance and believe they are having a good response, or they wouldn't keep taking it.

Now, the response could be real, or the people could have had milder MS anyway and it just looks like the drug helps. I don't know how the researchers can really control for this. One helpful clue might be if a large percentage of the original trial group, like 75% or more, made it to the long-term user category and showed good response. But if only a small number (10-20%) made it to the long term user group, this is not much greater than the number of people with "benign" MS" in the historical controls. I would be very interested to know the percentage of long-term users in relation to the total number at followup.

LisaBee

[Dunmann]

I agree, it seems a bit misleading. But when it comes to the CRABs, aren't they all misleading to an extent?

[TonyJegs]

Another tailored report and manipulation with numbers.

Disability score: 7% (several patients only) were slightly better after 16 years of treatment, survival number was a little bit better, but not impressive.
Interesting that they ‘forgot’ to mention that betaseron group consisted of 60% women (the number of women in betaseron group was greater than in control group), who have better outcome and survival rate anyway. If you recalculate this the results of this study will be awful, no real difference between treated and untreated patients.

There is more, practically all of betaseron taking patients took ibuprofen together (supposedly for side effect treatment), and this fact was muted as insignificant. As I have mentioned earlier, any kind of anti-inflammatory drug (in this case NSAID) will have positive effect on MS. Also they didn’t mention the number of dropouts, witch was significant, and this number was never added to side-effects group.

Kind regards,
Tony

[gwa]

I have never been on any of the CRABS and have always thought that I was in as good or better health than the groups that are using the drugs.

One thing that always catches my attention is the trials that report relapses that are cut in half in two years. I went from relapses of every three months the first year to about 2 the second year and less than one per year after 5 years.

The trial results do not beat that. Also, in this 16 year report, the time to cane usage in Beta users was 12 years. My time to cane use was 14 years, again better than the "average" Beta user.

Nothing I have ever read about the CRABS would make me take any of them . Many people believe in them and take them, but I will not take anything that does not make me better. By better, I mean something that alleviates or reverses my symptoms.

So far I do not see anything in the pipeline that will accomplish this.

gwa