Penwest Pharmaceuticals Co. halted development of its beta-blocker PW2101 after receiving a non-approvable letter for the drug in hypertension and angina.
In the letter, the FDA turned down PW2101's new drug application because of concerns regarding the degree of kinetic variability of the drug among individual patients, and because beta blockade could not be sufficiently demonstrated as a substitute for efficacy across the inter-dosing interval on an individual patient basis.
The Danbury, Conn.-based company declined to comment on the FDA's letter, though President and CEO Robert Hennessey said in a press release that it would not be in the firm's best interest to expend the time and resources needed to carry out "the additional activities we believe would be required."
Penwest's stock (NASDAQ:PPCO) lost 10 cents Thursday to close at $11.82, up 7 cents, after trading as low as $10.29.
The non-approvable letter seems to doom Penwest's marketing deal with King of Prussia, Pa.-based Prism Pharmaceuticals Inc. Signed in April, the agreement gave Prism rights to sell PW2101 in the U.S. and Canada, in exchange for a non-refundable up-front payment of $4 million, as well as up to $9.5 million in clinical and regulatory milestones, such as FDA approval by year's end, plus royalties of 15 percent to 18 percent.
When contacted by BioWorld Today, Prism representatives would not comment.
The FDA accepted the NDA in November for PW2101, a controlled-release formulation of an immediate-release beta-blocker. Data for the application included results from a pivotal trial, which evaluated PW2101 in four dosage levels and showed that volunteers given the low-strength version gained statistically significant reductions in exercise-induced heart rates.
At the FDA's request, Penwest conducted a second pivotal trial of low-dose PW2101 alone. That trial missed its primary endpoint of a change in the mean seated office-cuff diastolic blood pressure from baseline to week six, but hit the secondary endpoints, and those results were submitted for the agency's review.
With the discontinuation of the PW2101 program, Penwest intends to focus its resources on developing other products in its pipeline, specifically its early stage compounds aimed at treating central nervous system diseases such as depression, epilepsy and schizophrenia.
Results are expected in the fourth quarter from a 12-week Phase III trial with its oral, extended-release opioid analgesic, Oxymorphone ER, for moderate to severe pain in patients who need continuous opioid therapy over a long period of time. The firm's partner for that product, Endo Pharmaceuticals Inc., of Chadds Ford, Pa., received an approvable letter in October 2003, and reached an agreement with the FDA in December regarding protocol for a follow-up trial.
Penwest reported cash and investments totaling $66.8 million as of March 31 with a net loss of $8.9 million for the first quarter.