San Diego biotech Tracon has suffered a setback with a trial of its lead cancer drug carotuximab failing a phase 2 trial in a form of brain cancer.
The study—conducted by the National Cancer Institute (NCI)—showed that adding carotuximab to Roche's Avastin in patients with recurrent glioblastoma was no better than Avastin on its own in extending progression-free survival (PFS), although there was a trend toward an improvement in overall survival, said Tracon.
Analysts at Jefferies said the results were "somewhat discouraging" but said the overall survival data might indicate "a signal of activity," although they noted the trial was high-risk not factored into their forecasts for the drug. In particular, the target of improving on PFS by three months set the bar for showing an improvement "extremely high."
Investors were not optimistic about the prospects for the program, however, and shares in Tracon were down 13% in after-hours trading.
Tracon CEO Charles Theuer acknowledged that glioblastoma is a tough disease to crack with drug therapy, and said the company would present detailed survival analysis from the trial and other studies of carotuximab in other cancers later this year.
The drug (also known as TRC105) is an antibody targeting endoglin, a protein overexpressed on proliferating endothelial cells that is thought to play a role in the process of new blood vessel formation. Tracon hopes that shutting down the protein could help starve fast-growing tumors of oxygen and nutrients.
Jefferies still see potential in carotuximab, which they say has "multiple shots on goal" with potential in angiosarcoma, renal cell carcinoma (RCC), and gestational trophoblastic neoplasia (GTN) and approval chances of 40%, 25% and 30% respectively. Those three indications equate to a $1 billion-plus peak sales opportunity, they suggest.
"We expect a significant amount of data in the next 12-18 months, which should help determine TRC105's potential more clearly than this investigator-sponsored GBM study readout," they said in a client note.
Tracon recently said that carotuximab could become the first treatment specifically approved for angiosarcoma—an ultrarare cancer with few treatment options—if a planned phase 3 trial looking at the drug's activity when added to Novartis' Votrient (pazopanib) is successful.
Final phase 2 data in angiosarcoma is due later this year, along with interim midstage results in RCC, GTN and HCC data by YE17.
The company has other irons in the fire too, recently expanding its oncology pipeline by licensing two Janssen drugs—androgen inhibitor TRC253 for prostate cancer and NIK inhibitor TRC694 for blood cancers—due to start clinical trials in the coming months. Tracon will carry out preliminary testing with a view to relicensing them to Janssen if they clear proof-of-concept testing.
It is also developing TRC102, a small molecule DNA repair inhibitor that is in phase 2 testing for glioblastoma and earlier-stage studies in lung cancer, plus a Santen-partnered candidate (DE122) for wet age-related macular degeneration (AMD) that Jefferies says is an "overlooked program."