Monday, June 19, 1995
Positive data from clinical trials of two drugs for amyotrophic lateral sclerosis - Rhône-Poulenc Rorer's Rilutek and now Cephalon Inc.'s Myotrophin - raise for the first time the likelihood that there soon will be two drugs on the market to treat a previously untreatable disease.
While that's obviously welcome news, it also will complicate decisions for neurologists, who in both practice and theory will have few guideposts on deciding which drug to give, whether they should be given alone or in combination, or whether they should be given sequentially and if so in what order.
Complicating the equation will be the probability of overwhelming demand of desperate patients to use both. That may make it difficult or impossible to adequately test hypotheses about combination therapy, unless a combination trial can be started quickly, before both drugs are approved.
Few concrete conclusions
Conversations with six neurologists make it clear that patient demand will drive the market and that the neurology community is excited to at last have some treatment options. Thus, assuming that both drugs receive expeditious FDA approval, there seems to be little doubt that both will quickly garner sales.
Beyond those basic points, however, not much is clear. There is no consensus on whether Rilutek (riluzole) or Myotrophin (insulin-like growth factor-1, IGF-1) is the better drug, probably because each clinician was unable to render a confident opinion at this point. Thus there is no way as yet to predict a market winner.
Rather, neurologists are groping to understand what the trials will mean in clinical practice - particularly because they're not comparable.
In a nutshell, RPR's Phase III Rilutek trial in 959 patients led to a 17.4 percent increase in 12-month survival, and a 12.7 percent increase in survival at 18 months in patients taking 100 mg daily of the oral drug. No effect was seen in muscle function; side effects included nausea, fatigue and elevated liver enzymes. Barring a negative response from the FDA, a Treatment IND for the drug will go into effect this week.
Patients taking 0.1 mg/kg of IGF-1 in CEPH's 266-patient Phase II/III trial showed 25 percent less deterioration in muscle function after nine months. Although the trial wasn't designed to show a mortality benefit, a post hoc analysis showed a significant benefit for Myotrophin. The drug was well-tolerated. CEPH has indicated that following FDA approval, the company plans to launch a Phase IV trial to determine if a higher dose has a greater clinical effect.
Despite the relatively limited effects of each - Rilutek increases lifespan by three months, and Myotrophin slows progression on the Appel ALS Rating Scale by eight points - clinicians were cautiously optimistic about both drugs.