More MS news articles for July 2001

The price of success

Orphan Drug Act has spurred advances - and disputes

By Naomi Aoki, Globe Staff, 7/25/2001

he battle has been heating up for years. It has bounced from regulators to legislators, and now it has landed in the courts - all over the status of a drug approved to treat what was considered a rare disorder, a form of multiple sclerosis known as relapsing-remitting MS.

According to rules governing drugs for rare diseases, Cambridge's Biogen Inc. was granted a lock on the market until 2003. Unless Serono can prove its drug, Rebif, is better than Biogen's Avonex, the Swiss firm is barred from the $1 billion US market for multiple sclerosis drugs until Biogen's hold expires.

The case brings into bold relief the success of the Orphan Drug Act in spurring firms to develop drugs for rare diseases that once held little commercial value. In the 18 years since it was passed, more than 220 drugs have been approved for rare conditions and another 800 are in testing. By contrast, in the decade before the law was passed, less than a dozen drugs were developed for rare diseases. But the case also highlights the controversies that have arisen as a result of success. Under the act, the first company to reach the market with a drug for a rare disorder is granted seven years of market exclusivity. The exclusivity can only be broken if another version of the drug is proven safer, more effective, or significantly more convenient for patients.

Proponents of the act say it strikes a delicate balance, luring companies with the promise of profit while protecting patients' interests. Without the promise of exclusivity, they say, companies would abandon the costly research it takes to bring these drugs to market. And better drugs can always get to market, they say, ensuring patients access to the best medicine and encouraging companies to develop ever-more effective treatments.

But critics argue that the balance is askew. While the act works well in many cases, they say, it allows some companies to create unfair monopolies, gouge patients, and block competitors from the market.

''Some companies are going to be winners and some are going to be losers,'' said Abbey Meyers, president of the National Organization for Rare Disorders. ''A lot of biotech companies are willing to bet on being the winners. But if every runner-up wants to change the act, it will lose all its power.''

The situation is undoubtedly complex. The stakes are often life or death for patients, and in the hundreds of millions of dollars for companies. At an average cost of $170,000 for a year of treatment, Cerezyme, an orphan drug developed by Cambridge's Genzyme Corp. for an extremely rare inherited disorder known as Gaucher's disease, is among the world's most expensive drugs. But for the 2,500 Gaucher's patients on the drug, it is also a lifesaver.

Moreover, its success has enticed other companies to research diseases long ignored by drug makers - a fact underscored by the race between Genzyme and crosstown neighbor Transkaryotic Therapies Inc. to be the first, and perhaps sole, provider of a breakthrough treatment for another rare inherited disorder, Fabry disease. The two companies applied for regulatory approval for the nearly identical drugs within weeks of each other. And though approval for both drugs is expected in Europe, it could be a winner-take-all proposition in the United States.

For Meyers, the Serono-Biogen and the TKT-Genzyme cases are examples of the act's success. But she is acutely aware that success has its drawbacks. At a time when legislators are struggling with the expense of prescription drugs, Meyers said, these cases call attention to the sometimes intense competition for small markets that the Orphan Drug Act has created and the high cost of some orphan drugs.

''It's wonderful that there's more attention now to these types of diseases but it also raises lots of questions,'' Meyers said. ''People begin to wonder why these companies are racing each other for just a few hundred patients.''

The competition between Serono and Biogen is the most high-profile of these battles. Serono began lobbying legislators after failing to convince US regulators in 1999 that Rebif should be approved despite Avonex's orphan drug status, Meyers said. The company argued that the Food and Drug Administration had misinterpreted the act. Biogen's Avonex had reached the market by proving it was safer than an earlier version of the drug developed by Schering-Plough Corp. and approved in 1993. Serono argued that Avonex's exclusivity should only apply to its method of injection, the innovation that made it safer.

Meyers' group viewed the lobbying as a threat to the act and the future of orphan drugs. The changes Serono wanted, she contends, would only create uncertainty, discouraging companies from pursuing new and better orphan drugs. NORD ultimately thwarted legislative attempts to change the act. ''We don't need copies of the same drug,'' she said. ''What we need is better drugs. If Serono had come out with form of beta interferon [the active ingredient in Avonex] in a pill form, they'd be on the market today.''

So Serono set out to prove that Rebif is a better drug. With FDA guidance, it designed a clinical trial to compare Avonex and Rebif in a head-to-head study. The results released earlier this month lead to yet another round of wrangling in the years-long battle. Tom Lang, president of Serono's US division in Norwell, said the results clearly show that Rebif is more effective than Avonex after six months of treatment.

But Biogen, calling the data ''misleading,'' won an injunction from a Swiss court preventing Serono from making certain claims of superiority. Biogen has also asked prosecutors to investigate criminal charges against Serono for violating the injunction. The court battle is not an attempt to keep a better drug from US patients, said Tom Bucknum, Biogen vice president and general counsel. It is meant to protect Avonex's position in the European market, where doctors and patients can choose between the two drugs.

Bucknum contends that Serono employed a statistical method called an odds ratio to exaggerate the results. Serono's Lang counters that the odds ratio is a valid statistical tool agreed upon by the FDA. Bucknum also maintains that patients in the study on Avonex were sicker at the outset, skewing the results in favor of Rebif - an accusation Lang flatly denies.

Ultimately, the decision to approve Rebif in the United States rests in the FDA's hands. Serono will submit the latest results; it hopes to be on the market early next year. Even if its efforts are successful, however, Rebif will not be granted orphan drug status. In an ironic twist of fate, the number of patients diagnosed with relapsing-remitting multiple sclerosis has exceeded the 200,000 cutoff for orphan drug designation.

''The Orphan Drug law has so many benefits,'' Lang said. ''You look at it and see how many good things it does. If it doesn't work in one instance, that doesn't make it bad. But we've always felt Rebif should be available to patients in the US. ... The question is, `Where is the balance that allows more than one drug to be available yet still provides an incentive for companies to develop new and better drugs?'''

Naomi Aoki can be reached by e-mail at

This story ran on page F1 of the Boston Globe on 7/25/2001.
© Copyright 2001 Globe Newspaper Company.