- 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.
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.