Oxford GlycoSciences plc on Monday said the FDA issued word that Vevesca, the company's investigational drug for Gaucher's disease, is not approvable.
The negative news resulted in OGS's stock (NASDAQ:OGSI) falling 90 cents Monday, or 16.7 percent, to close at $4.50.
According to FDA regulations, the Oxford, UK-based company has 10 days from receipt of its "complete response letter" to either amend its application, withdraw it or request a meeting with the agency. The company submitted its application in August. (See BioWorld Today, Aug. 22, 2001.)
"Frankly, we don't have enormous comments over and above our press release. We do obviously have the opportunity to go and meet with the FDA, and that is a vital next step to really understand precisely where the areas of concern are in the package," Stephen Parker, chief financial officer of OGS, told BioWorld Today. "Really, until we've had the opportunity to sit down with the FDA, everything else is speculation, which is probably not helpful at the moment."
OGS's prepared statement said the FDA indicated that the new drug application (NDA) failed to provide sufficient evidence to claims that Vevesca was safe and efficacious.
Vevesca is an oral treatment for Gaucher's disease, a glycolipid storage disorder in which an enzyme deficiency leads to the accumulation of unmetabolized lipids. An approved intravenous enzyme therapy called Cerezyme, a product of Cambridge, Mass.-based Genzyme General, replaces the missing enzyme, while Vevesca acts by inhibiting glucosyltransferase, a key enzyme involved in the production of glycolipids, thus cutting the rate of glycolipid synthesis.
The company based its NDA on two trials. Study OGT 918-004 was designed to explore the use of Vevesca alone as an oral switch therapy and to investigate any benefits of co-administration with the enzyme, and the other, Study OGT 918-001, was a monotherapy study.
In the 36-patient Study OCT 918-004, the primary efficacy measure, liver volume, showed a statistically significant reduction from baseline to six months of minus 4.9 percent in the co-administration group compared to plus 3.6 percent in the control group. Quality-of-life data showed that patients in the Vevesca group reported significantly greater treatment convenience (p=0.028) and improvements in overall treatment satisfaction (p=0.053), compared to those who received Cerezyme.
In the monotherapy study, data were collected at 36 months on liver volume, spleen volume, hemoglobin concentrations and platelet counts. All four endpoints showed significant improvement over baseline using the "Last Observation Carried Forward" statistical analysis at a significant level of p<0.001, according to the company.
Parker said it is difficult to conduct trials in that indication because setting up a placebo group is almost considered unethical since it deprives ill patients of an already approved therapy. "So as a consequence, all of our trials are done without placebo and the inevitable consequence of this is that whenever you see any side effect, it is attributable to the drug group. Then, you have to put a great deal of effort into understanding just why that side effect might have occurred in order to have a demonstrated view or argument as to whether it is the drug, whether it is in the background of the disease or, of course, it could be a life event."
Furthermore, Parker said because Gaucher's is such a rare disease, it is extremely difficult to recruit enough patients to conduct an adequate trial.
OGS's worldwide target market for Vevesca totals about 10,000 people.
The company expects a decision on European regulatory approval in the third quarter.