Advaxis shares have fallen after the FDA placed a partial hold on its lead cancer vaccine axalimogene filolisbac (Axal).
The US drugs regulator has ordered all new recruitment into the pivotal phase 3 trial (AIM2CERV) to be suspended, triggering a 7% drop in the company’s share price yesterday.
The New Jersey based company was previously forced to halt two earlier clinical trials of Axal due to patient deaths. One of those trials involved a combination of Axal with AstraZeneca’s PD-L1 inhibitor Imfinzi for advanced, recurrent or refractory cervical cancer and HPV-associated head and neck cancer.
The patient died as a result respiratory failure nine months after being dosed with the combination treatment, but the hold was lifted in July last year under the premise that Advaxis would agree to new guidelines that would detect respiratory failure events. Although the company recently confirmed it would not continue enrolment of that study.
The FDA hasn’t cited any safety issues on this occasion, and enrolled patients will continue to receive treatment, but no new patients can enroll in AIM2CERV until the partial hold is resolved.
The FDA has requested additional data from AXAL’s chemistry profile, along with manufacturing and controls information, to decide whether the company can resume testing.
Shares were already well below cash value due to Amgen dissolving its $540m development deal with the company for an earlier stage immuno-oncology programme known as ADXS-NEO.
That partnership is due to end 8 February this year, and Advaxis confirmed that it is still enrolling patients for the early-stage trial, but it hasn’t reached a decision to find a new developmental partner for the programme.
The company says the partial hold has resulted from a trial re-design, which aimed to establish a more stringent futility boundary.
Axal is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralising the natural defences that guard the tumour microenvironment from immunologic attack.
Chief executive Kenneth Berlin (pictured below) said: “We have already begun efforts to address the Agency’s requests for information and are working to respond as promptly as we can.” He concluded, “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.”
The company’s hopes have rested on clinical data from ADXS-NEO trial, which were expected to be ready at the end of March this year, though this date may be revised due to the partial hold.