By Brady Huggett

Serono SA has been seeking a piece of the American pie for its product for relapsing-remitting multiple sclerosis, Rebif, since it filed its original biologics license application in the spring on 1998, but has been locked out through Biogen Inc.¿s orphan drug status on Avonex.

On Monday Serono confirmed that it submitted a supplemental BLA to the FDA in the third quarter and said it believes it has tendered all the information necessary to wedge itself into the profitable U.S. market.

The submission includes data from the Evidence (Evidence for Interferon Dose-effect: European-North American Comparative Efficacy) trial, the somewhat controversial head-to-head comparative study of Rebif vs. Avonex.

¿The statement [of filing] was a confirmation that we have filed the Evidence study report and takes the next step forward to bring Rebif to market for patients in the U.S.,¿ said Carolyn Castel, executive director of corporate communications at Norwell, Mass.-based Serono Inc., the U.S. arm of Serono SA. ¿The entire BLA, including the new amendment, answers all the requests for data the FDA has made in relation to Rebif ¿ everything that has been requested at this time is in the filing. Whether or not there will be any additional requests, only the future can tell us.¿

Peter Drake, an analyst for Prudential Securities Inc. in New York, said in a research note that Prudential expects Serono to submit 12-month follow-up data around year-end, adding to the sBLA. He also said the Evidence study showed ¿that high doses of Rebif¿ have a superior efficacy profile compared to Avonex ¿based upon reduction in the number of relapsing patients and brain lesions in the treatment of relapsing-remitting multiple sclerosis.¿

Drake anticipates Serono getting approval for Rebif before Avonex¿s orphan drug hold expires in mid-2003. Drake said in his note that Serono management has indicated that Rebif will receive an expedited review, and therefore, ¿well positions [Serono] for approval in the U.S. by mid-2002.¿

Serono, of Geneva, first brought Rebif for multiple sclerosis patients to the FDA in March 1998. The FDA did not approve the drug, saying the product didn¿t demonstrate the superiority needed for the FDA to override Biogen and Avonex¿s orphan drug status. (See BioWorld Today, March 4, 1998, and March 3, 1999.)

¿The BLA was not rejected and it remained an open file,¿ Castel said. ¿We¿ve had discussions with the FDA since that time.¿

What was needed was a trial directly pitting the drugs against each other, a study that would show definitely that Rebif is a superior product when compared to Avonex. The 24-week Evidence trial and its 677 patients set up that confrontation. However, data released from the trial were interpreted differently by the two companies and the battle over the U.S. market for the companies¿ multiple sclerosis products has grown into one of biotechnology¿s most heated. The companies have argued over delivery methods (Avonex is administered intramuscularly and Rebif subcutaneously) and the length of the six-month Evidence trial ¿ Biogen says six months is simply not long enough to prove anything when dealing with MS. Cambridge, Mass.-based Biogen even went so far as to file an injunction against Serono in Geneva attempting to prohibit Serono from disseminating claims stemming from the Evidence trial. (See BioWorld Today, May 9, 2001, and June 25, 2001.)

Rebif, a recombinant form of interferon beta-1a, works to retard the progression of MS.

¿In multiple sclerosis, the myelin sheath [covering nerves] is damaged because the immune system does not function properly,¿ Castel said. ¿Rebif helps to control the immune system and slow down the damage. But what is lost cannot be replaced, which is why you want to intervene early in the disease process, at the relapsing-remitting stage for Rebif.¿

Although not available in the States, Rebif is selling briskly worldwide. It is sold in 72 countries and generated $254.2 million in revenue for Serono in 2000. It brought Serono $90.7 million in the second quarter of 2001 and Serono¿s figures showed Rebif has 32 percent of the non-United States market. Serono has 16 products selling around the globe and had total revenues in 2000 of $1.2 billion. And with the supplemental BLA filed, those at Serono remain ¿cautiously optimistic,¿ Castel said, about the chances of getting Rebif into the United States before Biogen¿s orphan drug status expires.

¿Cautiously optimistic¿ applies to our case of being approved by the FDA in the time frame we have suggested of bringing Rebif to market by mid-2002,¿ Castel said. ¿We have taken this next important step for patients in the U.S. and we hope they will have this option available to them when they are speaking with their physicians.¿

Serono¿s stock (NYSE:SRA) climbed 22 cents Monday to close at $21.80.