Bayer’s pipeline has suffered another blow with the news that clotbuster alfimeprase, an enzyme developed by US partner Nuvelo that rapidly breaks down bloodclots by attacking their internal fibrin scaffolds, has fallen short in two Phase III trials.
Top-line data from a Phase III trial (NAPA-2) of alfimeprase in acute peripheral arterial occlusion (narrowing of the artery) showed that the agent did not meet its primary endpoint of avoidance of open vascular surgery within 30 days of treatment. The results are particularly dissappointing given that, in Phase II studies, the agent was able to restore arterial blood flow within a four-hour period post-dosing.
In addition, a second Phase III study (SONOMA-2) in catheter occlusion revealed that alfimeprase was unable to restore catheter function at 15 minutes. Both trials did not meet key secondary endpoints either, and the companies announced that they have temporarily suspended enrollment in NAPA-3 and SONOMA-3 follow-up studies.
Nuvelo’s chief executive Ted Love acknowledged that the findings were disappointing, and said the partners will conduct further analyses and have discussions with “outside experts and regulatory authorities to determine how to proceed with the development of alfimeprase, including the possibility of alternative dosing and delivery.”
Nuvelo stock plummets
Nuvelo’s stock sank on the news, falling over 80% at one stage, and, while Bayer’s share price was not heavily impacted, another failure in the clinic is unlikely to impress investors.
Only last week, Bayer and partner Onyx were rocked by clinical data from a Phase III trial which revealed that their potential blockbuster cancer drug Nexavar (sorafenib) was not effective in treating patients with advanced melanoma.
One firm pleased by the news will be Genentech. Its thrombolytic product Cathflo Activase (alteplase) is the only product approved for clearing catheter blockages, and it had been expected that alfimeprase would provide some serious competition.
Bayer and Nuvelo are not conceding defeat with the compound yet, and had previously hoped alfimeprase would have been worth hundreds of millions of dollars just in PAO, while studies in stroke and deep vein thrombosis were also planned.
Bayer licensed non-US rights to alfimeprase from Nuvelo at the beginning of this year in a deal that was potentially worth $385 million.