Days after stinging trial failure forced the California company to abandon its psoriasis program, FDA staff reviewers issued a review that highlighted the risk of neurological side effects with Durect Corp?s long-acting anesthetic, posimir, for patients with post-surgical analgesia.
Posimir, an extended-release formulation of the approved anesthetic ? bupivacaine ? has a checkered past. The company, which originally partnered with Novartis on the program, first submitted an application to market the drug on the basis of seven trials, including two pivotal studies in patients undergoing hernia repair and shoulder surgery. The FDA spurned the application in 2014 over safety concerns.
Durect then conducted another study, divided into two parts: a placebo arm and a comparator arm (bupivacaine). The comparator arm was added at the behest of the FDA ? and the company elected to discontinue the placebo arm. (The FDA said it considered the two arms as two separate studies).
Either way, posimir failed to induce a statistically significant difference against the placebo or bupivacaine in the trial, dubbed PERSIST. Some safety concerns, particularly neurological adverse events, also persisted, FDA staff noted in their review.
As noted in the 2014 complete response letter, FDA staff underscored the higher incidence of nervous system adverse events, such as somnolence, dizziness, and dysgeusia in patients given posimir.
Although Durect provided a rationale for the imbalance indicating it was due to the varied methods for adverse event collection, FDA reviewers appeared unconvinced. ?This represents another post-action analysis of data conducted by the Applicant instead of a prospective unbiased collection of data,? they wrote.
A panel of independent advisors is set to deliberate on the drug on Thursday. The FDA typically follows the panel?s recommendations but is not obligated to.
Stifel analysts, in a note earlier this month, estimated posimir has a meager 30% shot at approval in light of its difficult regulatory history.
In 2014, the FDA rejected the drug, citing a plethora of safety concerns including side-effects related to the shoulder joint and surrounding tissues; the risk of bruising, hematoma, pruritus among others; and a marked increased risk of neurological adverse events.
Durect appealed the decision ? and received an even more brutal response from the agency. ?I believe efficacy is present with Posimir but it is modest and inconsistent across different surgical procedures. My conclusion on efficacy preclude complete dismissal of the safety concerns raised by the Division,? wrote Mary Thanh Hai Parks, deputy director of the office of drug evaluation. Durect then conducted the PERSIST study, hoping to quell the agency?s concerns.
Meanwhile, in early January, the company?s experimental DUR-928 failed a mid-stage plaque psoriasis study. Last July, Gilead injected some confidence into the company?s HIV program, paying $25 million upfront and promising millions more in milestone payments to latch onto that platform.