A.P. Pharma Puts Off APF530 Launch To 2014 After Another FDA Rejection
This article was originally published in Pharmaceutical Approvals Monthly
Executive Summary
A.P. Pharma faces a second commercial setback as FDA issues another “complete response” letter for its long-acting granisetron in chemotherapy-induced nausea and vomiting.
A.P. Pharma is postponing its target launch date for its lead product, APF530, to the first half of 2014 from the second half of 2013, after receiving a “complete response” letter from FDA for prevention of chemotherapy-induced nausea and vomiting (CINV).
Announced on March 28, the “complete response” letter marks another rejection of the candidate, which is a subcutaneously delivered, long-acting formulation of the generic 5-HT3 antagonist granisetron, developed with the company’s Bichronomer drug delivery system. The product previously received a “complete response” letter from FDA in March 2010 and had been resubmitted in September 2012 (Also see "Setback for long-acting granisetron" - Pink Sheet, 1 Mar, 2010.).
The specialty pharma’s stock price was down about 36% to $0.37 on the news.
A.P. Pharma has been seeking approval for the drug for prevention of acute-onset CINV caused by moderately or highly emetogenic chemotherapy and delayed CINV related to moderately emetogenic chemotherapy. The NDA is supported by a pivotal study of more than 1,300 patients in which APF530 proved to be non-inferior to Eisai Co. Ltd.’s intravenous injectable Aloxi (palonosetron).
The company said it does not need to run any new clinical studies. However, it said that FDA has identified issues in three areas. On the chemistry, manufacturing and controls front, the agency has requested the “refinement of one product quality analytical test method” and identified deficiencies during facility pre-approval inspections.
FDA has also asked for a human factors validation study to test usability of the product syringe system with the commercial product.
And the agency wants a re-analysis of existing Phase III clinical data that reclassifies patients into those who received moderately emetogenic chemotherapy and highly emetogenic chemotherapy, in line with a guideline developed by the American Society of Clinical Oncology.
“In order to allow us time to carefully address the issues raised in the CRL, we are now projecting product launch for the first half of 2014, versus our prior guidance of the second half of 2013,” the company announced.
During a March 28 investor call, A.P. Pharma President and CEO John Whelan said that plans to correct the manufacturing deficiencies have been developed. “We believe those are being taken care of and will allow us to move forward with our manufacturing plan,” the exec said.
Whelan declined to provide details on the readiness of commercial product for the human factors study or the resubmission to FDA. Typically, an FDA review of a resubmission with significant new information would take six months to complete; simpler resubmissions have a two-month review clock.
As of the end of 2012, the company had $53.5 million in cash and cash equivalents. The company has hired senior commercial leadership for the launch, but has not yet employed a sales force.
“In light of today’s news, we of course plan to continue to carefully manage our cash resources,” Whelan said during the call.
A.P. Pharma sees unmet need for treatment of delayed CINV, as the only injectable currently approved by FDA for that particular CINV indication is Aloxi (see table).
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Intravenous Injectable 5-HT3 Antagonists: Approved Indications |
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Chemotherapy regimen |
Acute CINV |
Delayed CINV |
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Moderately emetogenic |
Roche’s Kytril (granisetron) GlaxoSmithKline’s Zofran (ondansetron) Eisai’s Aloxi (palonosetron) |
Aloxi |
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Highly emetogenic |
Kytril Zofran Aloxi |
None |
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Source: Adapted from www.appharma.com |
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