More MS news articles for June 2001

Results of Four-Year Study of Rebif(R) Published in Neurology

Serono Study Provides 'most convincing evidence yet that patients with relapsing-remitting MS treated with interferon beta will develop less permanent disability'(1)

http://finance.individual.com/display_news.asp?doc_id=PR20010628HSTH020&page=news

Thursday June 28  6:16am
Source: PR Newswire

GENEVA, June 28 /PRNewswire/ -- Serono S.A. (SWX Swiss Exchange: SEO and NYSE: SRA) An article published in this week's issue of Neurology(2) reports the results of PRISMS(3), a comprehensive four-year study of interferon beta-1a (Rebif(R), Serono) in the treatment of relapsing remitting multiple sclerosis (RRMS). The conclusions of the four-year study, involving 560 patients, give further support to the use of Rebif(R) at high dose (44mcg) three times per week. Moreover, the study provides evidence that early treatment of MS results in significant benefits over later treatment.

An accompanying editorial(1) describes the PRISMS study as providing "the most convincing evidence yet that patients with relapsing-remitting MS treated with interferon beta will develop less permanent disability." According to the study results, patients receiving high dose interferon beta-1a treatment for the full four years of the study had less impairment and disability than the low dose interferon beta-1a and placebo groups, and patients who received placebo for the first two years of the study never regained losses caused by delaying treatment.

Two-year data from the PRISMS study was published in The Lancet(4) in 1998. Adverse events during years three and four of PRISMS were similar to those observed in the first two years of the study with injection site inflammation and flu-like symptoms being the most common.

The PRISMS data has formed the basis for approval of Rebif(R) in 67 countries worldwide. Rebif(R) is currently not approved in the USA because a competitor product holds Orphan Drug status.

Earlier this year, Serono announced that, on the basis of the 4-year PRISMS data, the European Commission's CPMP(5) recommended the highest available dose of Rebif(R) (44mcg 3 times weekly) as first line therapy (compared to 22mcg 3 times weekly) for those RRMS patients using Rebif(R).

Background

Multiple Sclerosis (MS) is the most common disease of the central nervous system in young adults and it is estimated that up to two million people are affected worldwide, 450,000 of whom are in Europe alone.

Rebif(R) is currently the most frequently selected treatment for newly diagnosed MS patients in the world outside the USA. In 2000, Rebif(R) recorded worldwide sales of $254m.

Please see attached further details on the 4-Year Results of the PRISMS Study.

  1. Steven R. Schwid, MD; and Christopher T. Bever, Jr., MD. The cost of delaying treatment in multiple sclerosis, What is lost is not regained: Neurology 2001; June 26th; 56: 1620.
  2. The PRISMS Study Group and the University of British Columbia MS/MRI Analysis Group. PRISMS-4: Long-term efficacy of interferon-b-1a in relapsing MS: Neurology 2001; June 26th; 56:1628-1636.
  3. Prevention of Relapses and Disability by Interferon-beta-1a Subcutaneously in Multiple Sclerosis
  4. PRISMS Study Group Randomised, Double-Blind, Placebo-Controlled Study of Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis: Lancet 1998; November 8th; 352; 1498-1504.
  5. The CPMP is the committee responsible for providing scientific advice and opinions to the European Medicines Evaluation Agency (EMEA), within the framework of the European centralized approval procedure.
Some of the statements in this press release are forward looking. Such statements are inherently subject to known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements of Serono S.A. and affiliates to be materially different from those expected or anticipated in the forward-looking statements. Forward-looking statements are based on Serono's current expectations and assumptions, which may be affected by a number of factors, including those discussed in this press release and more fully described in Serono's Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on April 23, 2001. These factors include any failure or delay in Serono's ability to develop new products, any failure to receive anticipated regulatory approvals, any problems in commercializing current products as a result of competition or other factors, our ability to obtain reimbursement coverage for our products, and government regulations limiting our ability to sell our products. Serono has no responsibility to update the forward-looking statements contained in this press release to reflect events or circumstances occurring after the date of this press release.

About Serono

Serono, headquartered in Geneva, Switzerland, is a global biotechnology leader. The Company has six recombinant products on the market, Gonal-F(R), Luveris(R), Ovidrel(R), Rebif(R), Serostim(R) and Saizen(R), (Rebif(R) and Luveris(R) are not approved in the USA). In addition to being the world leader in reproductive health, Serono has strong market positions in neurology, metabolism and growth. The Company's research programs are focused on growing these businesses and on establishing new therapeutic areas. Currently, there are eleven molecules in development.

In 2000, Serono achieved worldwide revenues of US$1.240 billion, and a net income of US$301 million, making it the third largest biotech company in the world based on revenues. The Company operates in 45 countries, and its products are sold in over 100 countries. Bearer shares of Serono S.A., the holding company, are traded on the SWX Swiss Exchange (SEO) and its American Depositary Shares are traded on the New York Stock Exchange (SRA).

4-YEAR RESULTS OF THE PRISMS STUDY

Summary of results

The 4-year data from this study indicate that:

  • Treatment benefit with IFN-(beta)1a was maintained over 4 years.
  • High-dose IFN-(beta)1a, 3x44 mcg/week, was superior to 3x22 mcg/week on measures of disability, relapses, and magnetic resonance imaging endpoints.
  • Early treatment showed significant benefits over later treatment.
  • Placebo patients re-randomized to IFN-(beta)1a treatment demonstrated over 50% reduction in relapse rate.
  • IFN-(beta)1a was well tolerated at both doses.
Study objectives
  • To determine the long-term efficacy and safety of interferon (IFN)-beta 1a (IFN-(beta)1a; Rebif(R), Serono) administered subcutaneously three times a week for the treatment of relapsing-remitting multiple sclerosis (RRMS).
  • To assess the effects of high (3x44 mcg/week) compared with lower (3x22 mcg/week) doses of IFN-(beta)1a and the effects of early compared with delayed therapy.
Study design

Five hundred and sixty patients (389 females, 171 males) with RRMS and an EDSS score of 0-5 were initially randomized to receive IFN-(beta)1a, 3x22 mcg/week (189 patients), 3x44 mcg/week (184 patients) or placebo (187 patients) subcutaneously. After the first 2 years, placebo patients were re-randomized in a blinded way to receive one of the two active doses for an additional 2 years, while patients already on active treatment continued with the same dose in a blinded fashion.

After 2 years, a total of 506 patients (90%) remained in the trial and continued into the additional 2-year extension phase. Four hundred and forty-five out of 560 patients (79%) finished the 4 years of the study, demonstrating an excellent adherence to treatment and study protocol by patients and physicians over 4 years. All patients underwent clinical and neurological assessments every 3 months during the first 3 years and every 6 months during year 4, while MRI scans were performed at least every 6 months during the first 2 years and yearly thereafter.

Persistence of efficacy over 4 years

Even though biased against treatment, the Intention To Treat (ITT) analysis demonstrated highly significant treatment advantages of both doses of IFN-(beta)1a versus placebo on number of relapses, time to first and second relapse, and proportion of patients who were relapse-free during the full 4 years of therapy. Time to first confirmed progression was delayed by almost 12 and 18 months for patients on IFN-(beta)1a, 3x22 mcg/week and 3x44 mcg/week, compared with the placebo group. In addition, the total number of confirmed progressions was reduced.

Burden of disease was defined as the total area of lesions (abnormal plaques) in the brain, assessed using MRI scans. These were expressed as a percentage change from baseline. Natural-history studies indicate that untreated patients with RRMS show an increase in MRI burden of disease of 5-10% annually. Over years 1-4, patients who received placebo for 2 years and who were re-randomized to receive IFN-(beta)1a, 3x22 mcg/week and 3x44 mcg/week, for the last 2 years, demonstrated a median increase in burden of disease of 9.7% and 7.2%, respectively. Patients receiving IFN-(beta)1a, 3x22 mcg/week throughout, demonstrated a median increase in burden of disease of 3.4%, while those receiving 3x44 mcg/week showed a median reduction of 6.2%. There was also a sustained decrease in MRI activity over 4 years.

Dose-effect

The following outcomes showed a clear dose-response in this 4-year trial, with IFN-(beta)1a, 3x44 mcg/week, giving significantly (p<0.05) better results than IFN-(beta)1a, 3x22 mcg/week:

  • Total number of 1-point changes on disability progression scale
  • Time to second relapse
  • Relapse rate during years 3 and 4
  • Steroid use for MS
  • T2 active lesion count as measured by MRI
  • T2 lesion burden accumulation
Safety

The total exposure to IFN-(beta)1a during this trial was 1624 patient-years, and the total length of observation of all patients was 2015 patient-years. IFN-(beta)1a treatment at both doses was also well tolerated long term, and most of the adverse events reported were mild in severity. Only 7.5% of patients who received active treatment during the 4 years of study discontinued treatment due to adverse events. Side effects observed in the trial were generally those expected with interferon beta treatment. As expected, the effects most commonly attributable to active therapy were injection site reactions and flu-like symptoms. The great majority of side effects were not dose-related, with the exception of injection site reactions, asymptomatic decreases in white blood cells and platelet counts and asymptomatic increases in liver enzymes which were more common in the high dose group. The development of persistent neutralizing antibodies is associated with reduced efficacy.

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Source: Serono S.A.
Contact: Serono International S.A., Geneva, Switzerland, Media Relations, +41-22-739-36-00, or fax, +41-22-739-30-85, or Investor Relations, +41-22-739-36-01, or fax, +41-22-739-30-22; or Serono, Inc., Norwell, MA, Media Relations, 781-681-2340, or fax, 781-982-1369; or Noonan-Russo Communications, London, +44-207-726-4452, or fax, +44-207-726-4453, for Serono