Serono to Submit Data to FDA
Tuesday May 8
Source: PR Newswire
NORWELL, Mass. and GENEVA, May 8 /PRNewswire/ -- Serono S.A. (NYSE: SRA) and SWX Swiss Exchange: SEO)
Serono announced today the major outcomes of the direct comparative study between Rebif(R) (Serono S.A.) and Avonex(R) (Biogen Inc.) in patients with relapsing-remitting multiple sclerosis (RRMS). The primary endpoint of the study shows that patients treated with Rebif(R) have a 90% greater chance of remaining relapse-free during the period of observation compared to patients treated with Avonex(R). This result is highly statistically significant with a p value of 0.0005.
"We are pleased that the study endpoints as agreed with the FDA have been achieved. We will now progress our discussions with the Agency in our effort to make Rebif(R) available to patients in the USA as soon as possible," said Ernesto Bertarelli, Chief Executive Officer of Serono.
The EVIDENCE (EVidence for Interferon Dose-effect: 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 demonstrate the clinical benefit of Rebif(R) compared to Avonex(R) based on pre-defined FDA approved endpoints. The study was conducted with the concurrence of 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 magnetic resonance imaging (MRI).
The primary endpoint of the study is a comparison of the proportion of relapse-free patients after 24 weeks, expressed as an adjusted odds ratio. The resulting ratio is 1.9. This means that patients treated with Rebif(R) have a 90% greater chance of remaining relapse-free during the period of observation compared to patients treated with Avonex(R). This result is highly statistically significant with a p value of 0.0005. This finding is based on a 32% relative reduction in the proportion of patients experiencing relapses on Rebif(R) as compared to Avonex(R).
The main secondary endpoint is the reduction in combined unique lesion activity as measured by MRI over 24 weeks. Patients treated with Avonex(R) had 50% more new lesions in the brain than those treated with Rebif(R). This result is also highly statistically significant with a p value less than 0.0001.
677 patients with RRMS 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 or Avonex(R) (interferon beta-1a) 30 mcg once weekly. During the study, all assessing neurologists and radiologists were blinded from knowing which drug the patients were taking. The primary and main secondary endpoints are at 24 weeks, and both these endpoints have been achieved. The study follows patients for a total of 48 weeks.
Further details of the data on all endpoints of the EVIDENCE study will be announced on June 22 at a platform presentation during the World Congress of Neurology in London.
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, May 8, 2001, from 3:00 to 4:00 P.M. Central European Time (9:00 to 10:00 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 which interested parties may access via Serono's corporate home page, www.serono.com.
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 May 31, 2001. The telephone play back will be available until May 15 using the following numbers and a PIN code of 453#: +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.
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). 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).
Please see attached background information concerning:
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 in order to demonstrate its clinical benefit over Avonex(R) based on pre-defined endpoints. The pre-defined endpoints agreed with the FDA were:
Primary = The proportion
of relapse-free patients after 24 weeks, expressed as an adjusted odds
Main Secondary = The reduction in combined unique lesion activity 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
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) with Avonex(R) the adjusted odds ratio to remain free of relapses is 1.9. This means that patients treated with Rebif(R) have a 90% greater chance of remaining relapse-free during the period of observation compared to patients treated with 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 than the number of new lesions for Rebif(R) patients, indicating significantly more MRI lesion development with Avonex(R).
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 = 0.0005 and the main secondary endpoint had a p value of < 0.0001. Studies are considered positive if the p value is < 0.05. The EVIDENCE study is therefore very positive for Rebif(R) and highly statistically significant.
Source: Serono International S.A.
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