Death Forces FDA to Place Clinical Hold on Advaxis Cancer Drug

October 7, 2015
By Alex Keown, BioSpace.com Breaking News Staff

PRINCETON, N.J. – Following the death of a patient, the U.S. Food and Drug Administration (FDA) placed a hold on Advaxis ’s experimental cancer treatment axalimogene filolisbac, which is currently in mid-stage trials.

In a statement issued this morning, Advaxis maintains the patient’s death was a result of the severity of her cancer and not due to the company’s experimental cancer treatment. It is seeking proof from the FDA that the drug was not a factor in the death. Still, the hold on the experimental cancer drug will cause the company to halt four clinical trials, Advaxis said. Other clinical trials, including those with the experimental ADXS-PSA and ADXS-HER2, are not affected by this hold. The company said it will continue to actively enroll and dose patients.

The FDA placed a hold on the drug on Oct. 2 after the company submitted a safety report to the regulatory agency that week. The drug is being developed to treat patients with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC) who have progressed on at least one prior line of systemic therapy. Phase I trials released at the end of September showed treatment with axalimogene filolisbac resulted in a 38.5 percent 12-month overall survival rate in 26 patients. Patients typically fighting PRmCC who have failed at least one line of therapy have a typical survival rate of four to seven months.

PRmCC is a cancer associated with the Human papillomaviruses. There are several HPV vaccines on the market, including Merck & Co. ’s Gardasil, the top selling HPV vaccine, which sells for about $113 a dose. Cervical cancer impacts about 500,000 women per year and about half of those cases are terminal, according to the U.S. Center for Disease Control. The World Health Organization has recommended universal use of vaccines against the virus. In a 2014 report, the World Health Organization (WHO) projected worldwide cancer cases will increase by 57 percent over the next 20 years, from roughly 14 million diagnoses in 2012 to approximately 22 million.

Advaxis said the patient was diagnosed with end-stage cervical cancer who last received axalimogene filolisbac as part of an investigator-initiated trial in 2013. The patient was hospitalized in July 2015 and treated for Listeria monocytogenes. The cancer drug uses listeria to help trigger the body’s immune system to fight the cancerous cells. After a round of antibiotic treatment, the patient was discharged, Advaxis said. The patient was readmitted to the hospital in August 2015 with respiratory distress brought on by the cancer. The patient died that same day. Advaxis said investigations ruled the death was due to progression of her cervical cancer.

Advaxis said it is working with the FDA’s review and hopes the regulatory agency will quickly rule the drug did not play a part in the patient’s death.

“Advaxis expects that this clinical hold will be resolved expeditiously and without significant interruption to our HPV clinical development program,” the company said in a statement.

If the FDA allows axalimogene filolisbac to move forward, it will eventually take aim at leading Human papillomaviruses (HPV), which can lead to cervical cancer.