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TheStreet) -- The Biotech Stock Mailbag is open for business.
@BioPlays tweets, "Despite most of your voters forecasting a denial of DCTH at their AdCom and PDUFDA, I've yet to see/hear the bear case."
Fifty-four percent of contestants in the
FDA Drug Approval Contest believe
Delcath Systems(DCTH - Get Report) will receive a negative vote from the FDA advisory panel May 2. A subsequent FDA rejection garnered 64% of votes.
I'll do my best to explain the Delcath bear case, as I see it. [And for the record, I also voted for a negative panel and FDA rejection.]
Delcath's Melblez is a hybrid surgical-chemotherapy procedure in which the liver is isolated from the body's blood supply and bathed with high doses of the tumor-killing drug melphalan. Walling off the liver allows the melphalan to kill tumors without getting into the patient's blood stream and causing severe toxicity. Delcath is seeking approval for Melblez for the treatment of patients with unresectable ocular melanoma (skin cancer) that has spread to the liver.
Delcath conducted a single, phase III study of Melblez, randomizing 92 patients with ocular and cutaneous melanoma to treatment with Melblez or best alternative care (BAC.) The primary endpoint of the study was hepatic progression-free survival (hPFS), which measured the length of time before a patient's liver tumor began to grow again.
Results were first reported at the ASCO annual meeting in 2010. Melblez reduced the risk of liver tumor progression by 70%, which was highly statistically significant. At the median, hPFS was eight months for Melblez, compared with 1.6 months for BAC -- a difference of 6.4 months. The study met its primary endpoint.
A 2012 update from the trial showed a narrowing of the median hPFS benefit to 5.3 months (7 months vs. 1.7 months) and a 50% reduction in the risk of liver tumor progression -- but still statistically significant.
No survival benefit was reported. At the median, overall survival for Melblez patients was 9.9 months versus 9.8 months for BAC. Survival was confounded by 55% of BAC patients crossing over to receive Melblez therapy.
These data look pretty damn good, so why the negativity? The lack of a survival benefit raises concerns that the hPFS data are less than clinically meaningful. Patients treating with Melblez are not living longer. Delcath did conduct the Melblez study under a Special Protocol Assessment (SPA) agreement with FDA that OK'd use of hPFS as the primary endpoint. That works in Delcath's favor, but SPAs can be cast aside if the overall risk benefit is unfavorable. The lack of a survival benefit hurts Delcath, as does Melblez's inability to treat cancerous lesions outside the liver.