Shares of AstraZeneca $AZN started to slide this morning as the pharma giant confirmed that the FDA has placed a partial clinical hold on a Phase III research program involving its checkpoint inhibitor durvalumab, halting new enrollment.
The partial hold was instituted after investigators tracked bleeding events in a Phase III combo study for durvalumab, its top investigational drug, with tremelimumab for head and neck cancer. But the company cautions that all other studies are proceeding as planned, noting that such bleeding events are not unusual in head and neck cancer.
That said, AstraZeneca can ill afford any delays in the development of durvalumab now. The company already delayed its development timeline for the checkpoint inhibitor to allow for combination studies, which AstraZeneca is counting on to make a splash with a late arrival in the field.
A setback here will raise fresh questions for AstraZeneca as it attempts to play catch-up to the market leaders in checkpoint inhibitors. Durvalumab is now a distant fourth — or fifth — in the market, likely to follow Roche’s $RHHBY Tecentriq and well behind Merck ($MRK/Keytruda) and Bristol-Myers Squibb $BMY, which has racked up blockbuster sales with Opdivo.
AstraZeneca’s shares are down 5%.
The news about the safety issue has been percolating inside AstraZeneca for more than a month.
In a followup to a query, AstraZeneca said that they took the first step in pausing enrollment in mid-September, more than a month ago, then followed up with notices to regulators and investigators. According to a spokesperson:
The FDA recently confirmed their agreement with our action and placed a partial clinical hold on recruitment of new patients while we complete our analysis. We sent an update to ClinicalTrials.gov within the usual timeframes. Our analysis is now complete and has been submitted to FDA and under their review; we hope to resume [enrollment] as soon as possible.
$AZN let's not forget that both IO drugs are associated w/ colitis/gut perforations so together could lead to more bleeding incidences
— Sally Church (@MaverickNY) October 27, 2016
Here’s the full initial statement sent to Endpoints News:
Following the recent update on clinicaltrials.gov, AstraZeneca confirms that the US FDA has placed a partial clinical hold on the enrollment of new patients with head and neck squamous cell carcinoma (HNSCC) in clinical trials of durvalumab as monotherapy and in combination with tremelimumab or other potential medicines. All trials are continuing with existing patients.
The partial clinical hold on new patient [enrollment] relates only to head and neck cancer. Trials for durvalumab in different cancer types, as monotherapy or in combination with tremelimumab or other potential medicines, are progressing as planned, with pivotal data in lung cancer anticipated in the first half of 2017.
The FDA’s decision follows voluntary action by AstraZeneca to pause [enrollment] of new HNSCC patients while a detailed analysis is conducted of adverse events related to bleeding that were observed as part of routine safety monitoring of the Phase III KESTREL and EAGLE trials. Bleeding is a known complication in treatments of head and neck cancers primarily due to the nature of the underlying disease, the proximity of tumours to major blood vessels and use of prior cancer therapies, which may involve surgery and radiation.
AstraZeneca has submitted its analysis of the observed bleeding events to the FDA for review and is working closely with the Agency, providing the required information to resume new patient [enrollment] as soon as possible.
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