- AstraZeneca confirmed Thursday the Food and Drug Administration has halted enrollment of patients with head and neck cancer into studies of the British pharma's PD-L1 inhibitor durvalumab, sending shares sliding in Thursday trading.
- Routine safety monitoring turned up evidence of adverse events related to bleeding among patients with head and neck squamous cell carcinoma (HNSCC). The FDA's decision applies only to those patients; trials in different cancers are continuing as planned.
- AstraZeneca said it had voluntarily paused enrollment before the FDA's decision. The drugmaker has already submitted its analysis of the bleeding events to the regulator, but its not yet clear whether the events are linked to durvalumab itself or the combination drug.
Head and neck cancers, by their very nature, have an increased risk of bleeding during treatment as the cancer is near major blood vessels and the nature of typical prior treatments.
Still higher observed rates of bleeding could point to an adverse effect of treatment, something which could trip up AstraZeneca's push to win approval for durvalumab in that indication.
The partial hold was related to clinical trials of durvalumab both as monotherapy and in combination with tremelimumab.
AstraZeneca has pinned much of its hopes in oncology on durvalumab, hoping to join Merck, Bristol-Myers Squibb and Roche at the table in the checkpoint inhibitor market. Given the importance of the drug to future revenue growth, news of the partial clinical hold has naturally unsettled shareholders of the British pharma.
So far, the hold has no impact on the slew of other studies investigating durvalumab across a range of different cancers. And AstraZeneca said it continued to expect pivotal data in lung cancer sometime in the first half of 2017.
According to analysts at Jefferies, investors are particularly concerned about the impact on the MYSTIC study, which is testing durvalumab in first-line non-small cell lung cancer. This indication is considered to be one of the top markets for the checkpoint inhibitor drugs
The Jefferies analysts don't yet see a major impact, however, suggesting that any serious safety issues would already have emerged and that the bleeding in the head and neck study may even be a sign of efficacy relating to shrinkage and necrosis of the tumor.
This isn't the first stumble for the PD-L1 monoclonal antibody durvalumab, though. Last year, enrollment in a lung cancer study combining Tagrisso (osimertinib) and durvalumab in lung cancer was temporarily stopped after safety worries. Assessment of this combination in NSCLC is ongoing in the Phase 2 TATTON study.