More MS news articles for June 2001

Results of Evidence Study of Rebif(R) Versus Avonex(R) Presented at the World Congress of Neurology in London

Primary and Secondary Efficacy Data All Statistically in Favor of Rebif(R)

http://finance.individual.com/display_news.asp?doc_id=PR20010622HSF009&page=news

Friday June 22  8:01am
Source: PR Newswire

LONDON, June 22 /PRNewswire/ -- Serono Laboratories (UK) Ltd. (NYSE: SRA) (SWX Swiss Exchange: SEO)

Today, at the World Congress of Neurology in London, the results of the direct comparative EVIDENCE study between Rebif(R) (Serono Inc.) and Avonex(R) (Biogen Inc.) in patients with relapsing-remitting multiple sclerosis (RRMS) are being presented. These results provide strong evidence that Rebif(R) yields statistically significant benefits over Avonex(R) for all primary and secondary efficacy outcomes studied.

"The EVIDENCE study confirms the greater benefits of higher and more frequent doses of beta-interferon. This comprehensive and rigorous study has major implications for the optimal treatment of patients with multiple sclerosis," said Dr Patricia Coyle, Professor of Neurology and Director of the MS Comprehensive Case Center at the School of Medicine, Stony Brook, New York, who is the investigator presenting the study in London.

"The EVIDENCE study results are highly significant and further demonstrate the clinical efficacy of Rebif(R)," said Ernesto Bertarelli, Chief Executive Officer of Serono. "We will shortly be submitting this data to the FDA for their review in our effort to make Rebif(R) available to patients in the USA."

Summary of results

    REBIF(R) DEMONSTRATES CLEAR BENEFITS OVER AVONEX(R) WITH STATISTICAL
    SIGNIFICANCE ON ALL PRIMARY AND SECONDARY EFFICACY ENDPOINTS

Relapses

The primary endpoint of the study is a comparison of the proportion of relapse-free patients after 24 weeks expressed as an odds ratio. 25.1% of patients treated with Rebif(R) experienced a relapse during six months of treatment compared with 36.7% on Avonex(R), a relative difference of 32%. The adjusted odds ratio of relapse-free patients was 1.9 meaning that patients treated with Rebif(R) had 90% greater odds of remaining relapse-free relative to patients treated with Avonex(R). This result is highly statistically significant with a p value of 0.0005.

The average number of relapses during 6 months for patients treated with Rebif(R) was 0.29 and for those treated with Avonex(R) was 0.40, a relative reduction of 27% in favor of Rebif(R) (p value 0.022).

The relative risk of experiencing a relapse at any time within 6 months was 37% less for Rebif(R) patients relative to Avonex(R) patients (p value 0.001).

The need for steroids to treat relapses for the Rebif(R) group was 47% less, relative to the Avonex(R) group (p value 0.004).

MRI disease activity

The main secondary endpoint is the difference in combined unique lesion activity as measured by monthly MRI brain scans over 6 months. On average, patients treated with Avonex(R) had 50% more new lesions in the brain relative to those treated with Rebif(R). Rebif(R) treated patients had an average of 0.8 lesions per scan while Avonex(R) patients had an average of 1.2 lesions per scan. This result is highly statistically significant with a p value of less than 0.0001.

The proportion of brain scans per patient showing disease activity in the Rebif(R) group was 24.0% compared with 37.3% in the Avonex(R) group, a statistically significant reduction in favor of Rebif(R) (p value of less than 0.001).

The proportion of patients with no new disease activity, as measured by MRI, was 48.3% in the Rebif(R) group compared with 33.2% in the Avonex(R) group, a statistically significant difference in favor of Rebif(R) (p value of less than 0.001).

Safety and tolerability

Overall, 97% of patients completed 24 weeks on study with no statistically significant difference in withdrawal rates between the groups. Both formulations of IFN beta-1a were generally well tolerated. Although there were more injection site reactions and elevated liver enzymes associated with the higher and more frequent doses of Rebif(R) used, these were usually mild in nature. There were no cases of injection site necrosis with either medication.

Rebif(R)

Rebif(R) is registered in 67 countries worldwide and is currently the fastest growing treatment for MS outside the USA. In 2000, Rebif(R) achieved worldwide sales of $254.2m.

Conference Call and Webcast

Serono will hold a conference call today, June 22, 2001, at 4:30 P.M. Central European Time (3:30 P.M. London Time, 10:30 A.M. Eastern Daylight Time) during which Serono Management will present the outcome of the EVIDENCE study. To join the telephone conference please dial (+41.91.610.41.11 from Europe) and (+1.412.858.46.00 from the U.S.). The event will be relayed by live audio webcast (listen only mode) which interested parties may access via Serono's corporate home page www.serono.com . A series of slides will be available via the website at 14:00 CET.

A link to the webcast will be provided immediately prior to the event. Additionally, the webcast will be available for replay until close of business on 20th July 2001. The telephone play back will be available until 27th June 2001 using the following numbers and a PIN code of 320#: (+41.91.610.25.00 from Europe) and (+1.412.858.14.40 from the U.S.).

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 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). 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 are traded on the SWX Swiss Exchange (SEO) and its American Depositary Shares are traded on the New York Stock Exchange (SRA).

Please see attached background information concerning:

  • EVIDENCE study
  • Orphan Drug Status
  • Proportion of Relapse-free
  • Reduction in Combined Unique Lesion activity
  • P value
Background

EVIDENCE study

The EVIDENCE (EVidence for Interferon Dose-response: European-North American Comparative Efficacy Study) study is of particular interest as it marks the largest prospective comparative study of two disease modifying drugs in multiple sclerosis (MS).

The objective of the study was to investigate the clinical benefit of Rebif(R) compared to Avonex(R) based on pre-defined endpoints. The study was conducted following agreement with the FDA regarding its design, primary and secondary endpoints and the prospectively defined statistical analysis plan. It measured clinical endpoints as well as brain scan endpoints using monthly magnetic resonance imaging (MRI).

677 patients with RRMS, aged 18-55, at 56 centers in 9 countries in North America and Europe, were included in the EVIDENCE study. Patients underwent repeated clinical and MRI assessments while taking either Rebif(R) (interferon beta-1a) 44 mcg three times weekly by subcutaneous injection or Avonex(R) (interferon beta-1a) 30 mcg once weekly by intramuscular injection. During the study, all assessing neurologists and radiologists were blinded from knowing which drug the patients were taking.

Patients entered the study with an Expanded Disability Status Score (EDSS) of 0 to 5.5 and with clinically active disease defined as two or more relapses in the previous two years. There were no statistically significant differences in demographics or disease history between the randomized groups at baseline. Groups were comparable and characteristic of RRMS (75% female, late 30's, EDSS between 1 and 3).

The primary and main secondary endpoints are at 24 weeks, and both these endpoints were statistically significant in favor of Rebif(R). All other secondary endpoints over 24 weeks were also statistically significant in favor of Rebif(R). The patients are continuing treatment for a further 24 weeks. Data were analyzed on an intention-to-treat basis, which is the most statistically pure, unbiased method of analyzing study results.

Orphan Drug Status

Rebif(R) cannot currently be marketed in the USA. The Orphan Drug status of Avonex(R) is due to expire in mid 2003.

The terms of the Orphan Drug Act permit Rebif(R) to potentially enter the USA market before mid 2003, if Rebif(R) has been compared in a direct head-to-head study and successfully demonstrated its clinical benefit over Avonex(R) to the satisfaction of the FDA. The pre-defined endpoints in this study were:

  • Primary = The proportion of relapse-free patients after 24 weeks, expressed as an adjusted odds ratio.
  • Main Secondary = The combined unique lesion count as measured by MRI over 24 weeks.
The results of this study will be submitted to the Food and Drug Administration (FDA), as part of Serono's ongoing discussions with the Agency.

Proportion of Relapse-free patients

This is a clinical endpoint for the assessment of patients suffering from relapsing-remitting multiple sclerosis (RRMS). In the EVIDENCE study, clinicians assessed whether a patient had developed any new, acute worsening of disease or whether he or she had remained free of new exacerbations over a period of 24 weeks. Comparing Rebif(R) relative to Avonex(R) the adjusted odds ratio to remain free of relapses is 1.9. This means that patients treated with Rebif(R) had 90% greater odds of remaining relapse-free during the period of observation relative to patients treated with Avonex(R). The odds ratio is the number of patients who remained relapse- free divided by the number who had a relapse on Rebif(R), divided by the same ratio for Avonex(R).

Reduction in Combined Unique Lesion activity

This is a sensitive endpoint for measuring the amount of disease activity in the brains of patients suffering from RRMS. In the EVIDENCE study, patients were scanned using magnetic resonance imaging (MRI) every month for six months to determine how many new lesions appeared. A lesion is a new region of inflammation or damage to brain tissue. This particular endpoint of "combined unique lesions" provides maximum information about new MS activity in the brain as it measures activity using two types of complementary images (T1 and T2), yet it avoids double counting of lesions. The number of new lesions for Avonex(R) patients was 50% more relative to the number of new lesions for Rebif(R) patients, indicating significantly more MRI lesion development with Avonex(R).

P value

The p-value is a measure of the statistical probability that the outcome of a study is due to chance. In the EVIDENCE study, the primary endpoint had a p value of 0.0005 and the main secondary endpoint had a p value of less than 0.0001. Studies are considered positive if the p value is less than or equal to 0.05.

    For more information, please contact:
    Serono Laboratories (UK) Ltd.:

    Media Relations:      Investor Relations:     Noonan/Russo Communications:
    Tel: +44-20-8818-7200 Tel: +44-20-8818-7200   Tel: +44-207-726-4452
    Fax: +44-20-8818-7222 Fax: +44-20-8818-7222   Fax: +44-207-726-4453
    www.serono.com        Reuters: SEOZ.S/SRA.N   www.noonanrusso.com
                          Bloomberg: SEO SW/SRA US

    Serono, Inc., Norwell, MA
    Media Relations:
    Tel: +1-781-681-2340
    Fax: +1-781-982-1369
    www.seronousa.com

Source: Serono Laboratories (UK) Ltd.
Contact: Media Relations or Investor Relations, +44-20-8818-7200, or fax, +44-20-8818-7222, both of Serono Laboratories (UK) Ltd.; or Media Relations, Serono, Inc., Norwell, MA, 781-681-2340, or fax, 781-982-1369; or Noonan-Russo Communications, +44-207-726-4452, or fax, +44-207-726-4453, for Serono