ROCKVILLE, Md., March 11 -- The FDA has decided to allow a few patients with amyotrophic lateral sclerosis (ALS) access to mecasermin rinfabate (Iplex) under "compassionate use" rules.
However, with supplies of the drug extremely limited, access will be restricted to patients who have already filed requests. The FDA wants to reserve the remaining stock for a controlled clinical trial promised by the drug's manufacturer, Insmed.
This awkward situation arose because mecasermin rinfabate, a blend of recombinant insulin-like growth factor-1 (IGF-1) and IGF binding protein-3, was pulled from the market in 2007 when Insmed lost a patent dispute with companies that make a similar drug to treat stunted growth in children. Insmed has only a small quantity of mecasermin rinfabate remaining.
"The FDA believes its decision represents the fairest way possible to provide access to Iplex, first, because Insmed does not have enough drug for every patient who may request it and, second, because it is important to maximize what can be learned from the remaining supply of drug in case it does have benefit and could be further developed for widespread use by patients with ALS," the FDA announced in a statement yesterday.
In November 2008, under pressure from the Italian government, patients, and physicians, the other parties in the patent suit, Genentech and Ipsen/Tercica, agreed to permit Insmed to distribute its remaining stock of the drug to ALS patients under approved compassionate-use programs.
IGF-1 by itself had previously failed to show benefit in ALS in controlled studies, and some patient subgroups seemed actually to do worse on the drug.
Nevertheless, anecdotal reports of benefit in ALS with mecasermin rinfabate -- approved in the U.S. and elsewhere for treatment of pediatric growth failure with severe IGF-1 deficiency -- prompted patients and physicians to request the drug starting 10 weeks ago.
There is a strong demand for any drug that shows a glimmer of promise against ALS, the progressive neurological disorder also called Lou Gehrig's Disease. According to government and private estimates, ALS afflicts 20,000 to 30,000 people in the U.S. There are about 5,600 new ALS cases every year, and 5,000 deaths.
The FDA initially denied the latest requests from ALS patients because of the poor results from the early IGF-1 trials. The agency generally approves such requests only when it expects the manufacturer to pursue clinical trials and eventual marketing approval. That did not appear to be happening here, agency officials said.
"These concerns over single-patient access became more acute when we subsequently learned, as discussed above, that the supply of the drug is very limited," the FDA statement said.
But the agency changed its mind after reports that more than 100 ALS patients in Italy had received the drug under a court order. Insmed provided summary data showing that the Italian patients were not harmed by the drug, although there was no clear evidence of efficacy, either.
After Insmed told the FDA that it would like to pursue clinical development of mecasermin rinfabate for ALS, the agency agreed to allow distribution of the drug under the compassionate-use INDs -- but only those that had been already filed.
An FDA spokeswoman said the agency would not disclose how many such requests it had received.
The only way for new patients to gain access to the drug is through Insmed's planned clinical trial. Participants will be chosen by lottery, the FDA said.
Insmed said Ipsen/Tercica, which had won the patent infringement suit, had agreed to negotiate development of mecasermin rinfabate for ALS.
Ipsen/Tercica already markets a form of IGF-1 (Increlex) and initiated an ultimately successful patent infringement suit against Insmed.
The FDA's full statement on its decision is available at: