Dive Brief:
- New Jersey biotech Advaxis can continue a clinical trial of its lead candidate now that it has agreed to incorporate new guidelines for early detection of respiratory failure, a condition which led to a patient death earlier this year.
- The death occurred on Feb. 27, following nine months of treatment with a combination of axalimogene filolisbac and AstraZeneca's Imfinzi. In response, regulators placed a clinical hold on the Phase 1/2 trial, which had been testing the combo in patients with advanced, recurrent or refractory cervical cancer and human papillomavirus (HPV)-associated head and neck cancer.
- "We are pleased to have resolved this issue with the FDA and will implement these guidelines across Advaxis' portfolio as needed, to ensure patient safety," company CEO Kenneth Berlin said in a July 13 statement. So far, around 400 patients have taken the Advaxis drug, according to Berlin.
Dive Insight:
While the clinical hold may be lifted, Advaxis' stock value sure isn't. Share price did rise 31% to $1.60 apiece at market's open Friday, yet it's still a far cry from the 52-week high of $7.45 apiece seen last September. Over the past two years, the biotech's shares have lost about 90% of their value.
The drop reflects more than just concerns over axalimogene filolisbac too. None of the Advexis pipeline has made it to late-stage testing, and business updates have underscored that it could be some time before any hit the market. Additionally, it took nine months for Advaxis to find a replacement CEO after Daniel O'Connor left the position last July, further unsettling investor confidence.
Against that backdrop, Advaxis decided in June to lay off about a quarter of its workforce. It also said it would move resources away from axalimogene filolisbac and toward three other assets: ADXS-PSA, ADXS-HOT and ADXS-NEO — a strategy that seems to undercut Friday's positive news of the revoked clinical hold.
The first of those assets is in a Phase 1/2 study evaluating it alone and paired with Merck & Co.'s Keytruda (pembrolizumab) in prostate cancer patients. The second targets neoantigens, with an initial focus on the solid tumors seen with colon, head and neck, and non-small cell lung cancers. The third also targets tumor-associated antigens and is pre-clinical.
Along with its June announcement, Advaxis revealed it was looking for development partnerships for axalimogene filolisbac in HPV-associated cancers. If the partnerships don't materialize fast enough, however, Advaxis intends to "wind down" its AIM2CERV trial of high-risk locally advanced cervical cancer and scrap plans for another combo trial in metastatic cervical cancer patients. The biotech added that it was still interested in "cost-effective" investigations of the drug in HPV-positive head-and-neck cancer.
Though Advaxis leadership clearly sees less promise in the company's lead candidate, analysts haven't been so quick to judge.
In fact, Jefferies analyst Biren Amin acknowledged in a March note how Imfinzi (durvalumab) has a history with respiratory failure. In the drug's Biologics Licensing Application, for instance, safety data indicates there's an 0.8% death rate within 30 days because of the condition.
That also matches up with reports that 1% of patients in trials for Imfinzi, Keytruda and Pfizer and Merck KGaA's Bavencio (avelumab) experienced serious cases of respiratory failure, "suggesting 1% incidence across most PD-1/L1s," Amin wrote. "In some cases, the [serious adverse events] were reported as cardiorespiratory arrest, which suggests cardiac etiology and would also align [with] hypotension as reported for the deceased patient in [the combo trial of Imfinzi and axalimogene filolisbac]."
Notably, the clinical hold for that trial didn't affect enrollment and dosing in any other programs for Advaxis' drug or Imfinzi.