Drug Development, Regulatory

Patient death forces FDA to slap a hold on study using combo from Advaxis, AstraZeneca — biotech’s shares plunge

The FDA has slapped a clinical hold on a combo therapy using Advaxis’ $ADXS axalimogene filolisbac along with AstraZeneca’s approved PD-L1 Imfinzi following the death of a patient in their Phase I/II trial.

Researchers were studying the combination of drugs for patients with HPV-triggered head-and-neck as well as cervical cancer. In this particular case, a patient died from respiratory failure following the 6th treatment cycle. And now regulators want to put the study on hold while they examine the implications for others in the trial.

The news triggered a sharp 31% drop in Advaxis’ shares after the market closed.

Anthony Lombardo

The two developers partnered more than three years ago, while Imfinzi was still an experimental therapy. The AstraZeneca drug works by taking the brakes off an immune system attack on cancer cells. Advaxis’ drug uses a live, engineered strain of Lm bacteria to kick up an immune response while targeting defensive mechanisms in cancer cells. Just a few days ago Advaxis filed for conditional marketing approval in the EU for use against cervical cancer.

Advaxis learned about the hold on Friday, 10 days after the patient’s death.

In a quarterly call with analysts on Monday, Advaxis’ Robert Pettit explained that the patient has been in the study for more than a year. He added:

So in this particular case, she received her first drug which was durva. She started developing some medical problems in between that were managed, then she started to receive the second dose. Afterwards, she received the second drug, which was AXAL. She was being managed for hypotension aggressively and was subsequently hospitalized. While she was hospitalized, she developed respiratory failure and subsequently expired despite methods to stop the progression of her disease. That’s really all the information we have at this point.

While trial deaths in studies using CAR-T drugs are not unusual, the checkpoints have been going into hundreds of combination studies without raising a lot of safety issues — aside from combos using Celgene’s Revlimid and Pomalyst with Merck’s Keytruda, where an imbalance in patient deaths triggered concern. That caused a blanket pullback involving similar checkpoint combos, but after the FDA determined there likely was no class effect involved, most of those studies were allowed to get back into the clinic.

Advaxis is also partnered with Bristol-Myers on an Opdivo combination program, which followed a separate alliance with Amgen.

This isn’t the first study using their drug, and the biotech tried to reassure investors about its safety.

“We care deeply for our patients and for their safety as we work to research and develop new treatment options for advanced cancers. We believe in the potential of our Lm Technology to provide new advancements in the area of cancer care,” said Advaxis CEO Anthony Lombardo in a statement. “We are confident in the safety and efficacy profile of axalimogene filolisbac, to date, based on our experience in over 250 patients and over 700 doses across multiple trials in HPV-associated cancers.”


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