August 18, 2016
By Mark Terry, BioSpace.com Breaking News Staff
South San Francisco, California - Portola Pharmaceuticals announced today that the U.S. Food and Drug Administration (FDA) had rejected its AndexXa to treat life-threatening or uncontrolled bleeding.
AndexXa (andexanet alfa), which was an FDA-designated Breakthrough Therapy, was being evaluated in patients treated with a direct Factor Xa inhibitor like apixaban, rivaroxaban, or deoxaban, or an indirect Factor Xa inhibitor like enoxaparin when “reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.” The company had submitted an application for a Biologics License Application (BLA).
In the FDA’s Complete Response Letter (CRL), it asked the company to provide more information mostly related to manufacturing activities related to AndexXa. It also requested more data related to including edoxaban and enoxaparin in the label. The FDA also said that it wanted to finalize a review of the clinical amendments related to the company’s post-marketing commitments.
“Because AndexXa addresses an urgent unmet medical need, we and the FDA are committed to resolving the outstanding questions and determining appropriate next steps,” said Bill Lis, Portola’s chief executive officer, in a statement. “Portola’s goal is to define the most expedient path to approval so we can meet the needs of these patients who have no alternative. We plan to meet with the FDA as soon as possible.”
Some of the data originally included was from the company’s Phase III ANNEXA-A trial. ANNEXA-A showed that the drug quickly reversed the anticoagulant effect of apixaban, which is Pfizer and Bristol-Myers Squibb ’s Eliquis, by 93.5 percent. And apparently it sustained most of its efficacy over a two-hour infusion period.
Portola dropped to $19.50 at the news. Shares traded at $56.90 on Sept. 18, 2015, dropped to $51.66 on Dec. 30, 2015, and plunged to $19.01 on Mar. 28, 2016. Shares traded at $27.69 on Aug. 15 before the news broke.
At the company’s second quarter financial report on Aug. 9, Portola also provided updates on Betrixan, an oral Factor Xa inhibitor to prevent venous thromboembolism (VTE) in acute medically ill patients, which has a Fast Track status from the FDA. It is planning to present full results of the Phase III APEX trial at the ISTH SSC Meeting, and submit a New Drug Application (NDA) and an MAA in Europe later this year.
At the conference call, Portola repeated its plans to submit an NDA for betrixaban. In a Phase III trial, the drug did not hit statistical significance, which also forced down company stock. Mark Collins, writing for Market Exclusive, actually believes that the problem here isn’t the drug, but a problem with the trial design. “Without the enriched setup, the drug would have met its primary endpoint and markets would probably be buying into Portola ahead of the planned NDA submission. Instead, markets have sold off on the company, and it has somewhat fallen off the radar.”
Although today’s news certainly didn’t help matters. More details are probably needed to completely understand whether the FDA’s CRL for AndexXa is related to problems with the drug itself, or with something related to manufacturing.
Portola also provided information about Cerdulatinib, an oral, dual Syk/JAK inhibitor to treat resistant or relapsed hematologic cancer patients. It recently presented outcomes data from a Phase I study at the ASCO Annual Meeting, at the EHA Congress, and started enrollment in a Phase IIa trial. It expects to present early data from that trial later this year.
The company also stated, “Collaboration revenue earned under Portola’s collaborations with Bristol-Myers Squibb and Pfizer, Bayer Pharma and Janssen Pharmaceuticals, Daiichi Sankyo and Lee’s Pharmaceutical was $4.2 million for the second quarter of 2016 compared with $2.4 million for the second quarter of 2015. The increase in revenue was primarily due to a collaboration and license agreement that Portola entered into with BMS/Pfizer to develop and commercialize andexanet alfa in Japan and a clinical collaboration agreement that Portola entered into with Bayer to include its Factor Xa inhibitor in the andexanet alfa development program in Japan.”
