Citing the urgent unmet need for patients with advanced biliary tract cancer, Compass Therapeutics will continue to seek an approval path for its drug after the FDA recommended the biotech conduct a new clinical study.
The FDA has recommended that Compass Therapeutics conduct a new clinical trial and show a survival benefit for the bispecific tovecimig in advanced biliary tract cancer before submitting the drug for review—but the biotech will proceed with the biologics license application anyway.
The situation is not without precedent, according to Leerink Partners, which pointed to a similar situation underway with Summit Therapeutics.
An additional study would likely represent a three-year delay for Compass, the firm noted, emphasizing that the agency simply recommended a study but did not say it was mandatory before the BLA filing.
Shares of Compass dipped nearly 30% to $1.29 on Tuesday morning. The company’s stock has fallen 75% year to date, from a high of about $6.70 in February.
The data from the Phase 2/3 COMPANION-002 trial for tovecimig were “confounding,” Compass said when it reported the results in April. The drug met the main goal of improving progression-free survival (PFS) in patients with advanced biliary tract cancer (BTC). Participants in the treatment arm had an average PFS of 4.7 months, compared with 2.6 months for those in the control arm. But the secondary endpoint of overall survival was not met. Analysts at the time dubbed the readout a challenge for an upcoming FDA application.
Now, the FDA has balked at the data too, according to Compass’s Tuesday release. After discussions last month, the FDA has recommended that Compass conduct a new trial to show an overall survival benefit.
Compass noted that the COMPANION-002 study showed an objective response rate of 18% in patients who took tovecimig plus chemotherapy as compared to 5.3% in those who only received the chemo. The PFS data also suggest a 56% reduction in the risk of disease progression.
“Overall survival (OS) analyses were confounded by both high crossover and notably prolonged survival in crossover patients randomized to the control arm then treated with tovecimig and, therefore, did not meet statistical significance,” Compass said in Tuesday’s release.
Compass intends to press forward with the BLA even with the new request and promised to engage with the FDA to find a path forward.
“While this is not the response we expected, we respect the FDA’s feedback and our priority is to work with the agency to determine the best path forward to support our planned BLA submission and address this pressing unmet need,” CEO Thomas Schuetz said in a statement. “We remain confident that the COMPANION-002 findings, including the statistically significant improvements in PFS and ORR combined with subset analyses on survival, demonstrate clinically meaningful activity in patients with previously treated, advanced BTC.”
Leerink pointed out that the FDA has not requested a new study to establish safety or clarify potential toxicities, which could mean that Compass can indeed navigate this speed bump.
“CMPX is seeking to re-engage with the FDA, and pull all levers (citizens’ petition, etc),” the firm wrote.
Compass could file the application at risk, which is what Summit has done for its Akeso-partnered ivonescimab in EGFR positive non-small cell lung cancer. As with Compass, the FDA requested that Summit conduct an additional study to demonstrate overall survival before applying for approval for the PD-1/VEGF asset on the U.S. markets. The company did not conduct a new trial, yet the FDA accepted the BLA and has set a decision date of November 14.
Leerink will be watching that decision closely for readthroughs to Compass. The situation could also be helped if the agency chooses to convene an advisory committee meeting for tovecimig’s application.
Replimune emerged victorious after such a meeting earlier this year was held to consider the melanoma drug now approved as Tudriqev. Agency leaders had previously determined that Replimune’s data package was “insufficient to conclude substantial evidence of effectiveness.”
