No safety issues were cited. Instead, it appears related to the company’s proposal to modify the trial’s analysis plan and various chemistry, manufacturing and controls (CMC) issues.
The U.S. Food and Drug Administration (FDA) placed Princeton, NJ-based Advaxis’ Phase III clinical trial of axalimogene filolisbac (AXAL) in advanced cervical cancer on partial clinical hold.
No safety issues were cited. Instead, it appears related to the company’s proposal to modify the trial’s analysis plan and various chemistry, manufacturing and controls (CMC) issues. The trial is an ongoing randomized, double-blinded, placebo-controlled, pivotal trial of AXAL in high-risk, locally advanced cervical cancer (AIM2CERV).
The partial hold means no new patients can enroll in the trial until the hold is lifted.
“FDA’s review of the AXAL Investigational New Drug (IND) application was prompted by our proposal to modify the AIM2CERV trial’s analysis plan to include, among other things, allowance for a second formal interim analysis for both safety and efficacy,” stated Kenneth A. Berlin, Advaxis’ president and chief executive officer. “The primary focus of the items raised by the Agency relates to providing additional clarifying details for CMC information previously provided in support of Phase III development and which will help support a future Biologics License Application.”
Berlin went on to say that they have already started on responding to the FDA. “Our AXAL product has demonstrated a manageable safety profile in the over 400 patients we have dosed to date and we look forward to enrolling new patients in our AIM2CERV trial after FDA agrees that the information we submit is responsive to its requests.”
Cervical cancer is the most common human papilloma virus (HPV)-associated cancer in women. Each year, about 4,210 women die from cervical cancer in the U.S. There are slightly under 13,000 newly diagnosed cases each year.
AXAL has shown in earlier trials and preclinical studies to alert the body’s immune system to the presence of the cancer and reduce the cancer’s natural defenses, then stimulate the body’s killer T-cells to attack the cancer. AXAL targets HPV-associated cancers. The FDA has given it orphan drug designation and a Special Protocol Assessment for the Phase III AIM2CERV trial, as well as Fast Track Designation.
The company’s technology uses live attenuated Listeria monocytogenes engineered to produce antigen-adjuvant fusion proteins.
This is only the most recent setback Advaxis has faced. In mid-December 2018, Amgen walked away from an immuno-oncology partnership the two companies had. The companies were working to develop ADX-NEO, a preclinical program that used Advaxis’ Listeria monocytogenes bacterial vector. The partnership was going to end Feb. 8, 2019. It began in 2016 and was valued at up to $540 million. Amgen paid $40 million up front and acquired $25 million of Advaxis common stock at the time.
In the filing with the U.S. Securities and Exchange Commission, Advaxis indicated it had received reimbursement payments of $5.8 million and $7.5 million related to the deal.
In March 2018, the FDA halted a clinical trial of AXAL with AstraZeneca’s Imfinzi (durvalumab) for advanced, recurrent or refractory cervical cancer and HPV-associated head and neck cancer. This followed the death of a patient. The patient died from respiratory failure nine months after receiving the combination treatment. The hold was lifted in July.
To lift that hold, the FDA and Advaxis developed new guidelines for the trial that assisted with the early detection and treatment of “such rare events.” But in November, the company announced it would halt enrollment in the Phase I/II trial combining AXAL and Imfinzi in order to “maximize the efficient use of clinical funding resources.”
