Advaxis disclosed yesterday that the FDA has placed its IND application for axalimogene filolisbac (formerly ADXS-HPV) on clinical hold on October 1, after the agency received a safety report on the death of a patient treated with the cervical cancer immunotherapy in a clinical study two years ago.

The safety report focused on a female patient with end-stage cervical cancer who last received axalimogene filolisbac in early 2013 in an investigator-initiated trial. The patient was hospitalized for end-stage cervical cancer symptoms in July of this year.

During her hospital stay, routine blood cultures revealed the presence of Listeria monocytogenes (Lm), Further tests showed the Lm to be the highly attenuated strain used in axalimogene filolisbac, which according to Advaxis was incapable of causing infection and was highly sensitive to antibiotics. The patient received a course of intravenous antibiotics and was discharged.

But in mid-August, Advaxis said, the patient returned to the hospital with respiratory distress caused by her metastatic disease. She died later that day. The trial investigator found that the cause of death was progression of her cervical cancer.

“The company has evaluated this case and agrees with the investigator’s conclusion that the cause of death was due to cervical cancer progression. The company believes that axalimogene filolisbac played no role in the patient’s death,” Advaxis declared in a statement.

The company cited the patient’s undergoing “multiple” surgical procedures while receiving axalimogene filolisbac—including extensive orthopedic reconstruction and receipt of a bone graft and other medical implants. Advaxis asserted that the implants could have provided a location for axalimogene filolisbac to exist within the body without causing any infection.

Advaxis acknowledged that the FDA has requested of it additional data to support a finding that axalimogene filolisbac did not contribute to the patient’s death.

“This additional information has now been provided to the FDA,” the company said. “Advaxis expects that this clinical hold will be resolved expeditiously and without significant interruption to our HPV clinical development program.”

Investors responded to Advaxis’ announcement of the clinical hold, timed after the close of the markets yesterday, with a sell-off that lowered the company’s share price nearly 26%, from the Tuesday closing price of $10.31 to $7.65 in after-hours trading. Shares bounced back to $10.13 as of 10:02 a.m. today.

Axalimogene filolisbac is Advaxis’ lead Lm Technology™ immunotherapy candidate for human papilloma virus (HPV)-associated cancers, with clinical trials in progress for three potential indications: Phase II in invasive cervical cancer, Phase I/II in head and neck cancer, and Phase I/II in anal cancer. FDA has granted axalimogene filolisbac orphan drug designation for all three indications.

In a completed randomized Phase II study in recurrent/refractory cervical cancer, axalimogene filolisbac showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy. Those results supported further development of the company’s Lm Technology™, the company said.

Advaxis is developing multiple cancer immunotherapies based on Lm Technology, which uses bioengineered live attenuated Lm bacteria. According to the company, Lm Technology is the only known cancer immunotherapy agent shown in preclinical studies to both generate cancer fighting T-cells directed against a cancer antigen, and neutralize Tregs and myeloid-derived suppressor cells (MDSCs), which protect the tumor microenvironment from immunologic attack and contribute to tumor growth.

According to Advaxis, ongoing clinical trials with its other product candidates— ADXS-PSA for prostate cancer and ADXS-HER2 for HER2 expressing solid tumors—are not affected by this hold and continue to actively enroll and dose patients.

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