The Food and Drug Administration is bringing together experts next week to advise the agency on whether to approve a version of
Pompe disease drug Myozyme that will be made a new, larger facility.
Briefing documents for the Oct. 21 advisory panel, posted Friday, suggest Genzyme may be facing more concerns than previously expected, according to some Wall Street biotech observers.
Genzyme does not have enough manufacturing capacity to produce all the Myozyme it requires to treat patients with Pompe disease, a severe and progressively debilitating inherited neuromuscular disorder that affects a very small number of people throughout the world.
Efforts to convince the FDA to approve the new version of Myozyme made at a larger manufacturing facility have run into delays. Last April,
was forced to reduce its 2008 earnings guidancewhen the FDA asked for more clinical data on the updated Myozyme.
The FDA is expected to decide on whether to clear the new version by Nov. 29. Approval is a critical factor for Genzyme's revenue and earnings growth, which is why next week's advisory committee meeting to review the drug is so important.
"It's not a slam dunk for Myozyme at this point," said Lazard Capital analyst Matthew Osborne. "
The FDA raised a lot of concerns regarding the
trial endpoints -- if they were clinically meaningful, the magnitude of response and the insufficient number of patients less than 18 years."
To get a large-scale Myozyme manufacturing facility approved,Genzyme provided the FDA with data from a clinical study, dubbed LOTS, that enrolled 90 patients, 81 of whom completed the study.
In the review posted to the FDA Web site Friday, the agency's advisers raised worries that Genzyme changed some of the targets used in the LOTS trial. FDA staff members noted that while they have agreed to use those endpoints, which were the same ones Genzyme used for other enzyme therapies, they aren't established in Pompe disease or any other lysosomal storage disorder.
The main efficacy endpoints are now a six-minute walking test and a measure of the total amount of air that a person can forcibly blow out after inhaling as much air as possible.
"These co-primary endpoints were prospectively agreed upon with the FDA and are considered the most clinically relevant measures of walking ability and pulmonary function, respectively, for patients with late-onset Pompe disease," Genzyme wrote in a press release later in the day.
According to an FDA analysis, although patients in the Myozyme arm of the LOTS study showed an improvement in the rate of change of their walking distance in the six-minute walking test, the result wasn't statistically significant.
Genzyme countered that it learned just this week that the FDA would use a secondary, sensitivity analysis as the primary analysis for the six-minute walk test, for discussion at the panel. The company believes the use of the sensitivity analysis isn't appropriate, and that the prespecified primary analysis demonstrated the effectiveness of the new Myozyme.
Even so, Deutsche Bank's Mark Schoenebaum pointed out in a note to investors that two other orphan drugs, Aldurazyme and Elaprase, had similar main endpoints, and in both cases only one of those goals was reached with statistical significance. Despite missing one endpoint, both drugs were approved.
"We believe these cases provide precedence for approving a drug for an orphan disease without significance shown for both co-primary endpoints," he writes.
The panel will also discuss the age representation of the participants in the study. "Although patients with Pompe disease 8 years and older were eligible to participate in LOTS, very few patients less than 18 years of age at the time of diagnosis and/or onset of symptoms were actually enrolled," FDA reviewers stated. "This substantially limited the trial's ability to support the efficacy of 2000 L
Myozyme in juvenile-onset patients."
"Overall, the documents look negative to us, with questions regarding efficacy and immunogenicity bringing serious questions on the immediate approvability of this drug," said J.P. Morgan analyst Geoffrey Meacham in a Friday research note. Meacham has a neutral rating on Genzyme.
Genzyme shares were down $2.47, or 3.8%, at $63.31, Friday.