Prostate cancer ADC acquired from Fortis breaks FibroGen's clinical losing streak

FibroGen had a run of bad luck in its phase 3 trials last year, but phase 1 data posted this week suggest its earlier-stage pipeline still has potential.

A phase 1 study of the anti-CD46 antibody drug conjugate (ADC) FG-3246 in 56 patients with metastatic castration-resistant prostate cancer demonstrated median progression-free survival (PFS) of 8.7 months and a prostate-specific antigen (PSA) decrease of 50% or more in 36% of participants.

William Blair analysts branded the results “encouraging” and said they “appear to offer numerically improved efficacy metrics relative to alternate novel hormone therapy.”

They also noted that Novartis’ radioligand therapy Pluvicto scored a PSA50 response of 58% and a PFS of 12 months in a phase 3 trial among a similar patient population, while a combination of Exelixis’ Cabometyx and Roche’s Tecentriq demonstrated PFS of 4.2 months in a separate phase 3 prostate cancer trial.

“While we acknowledge that the FDA cautions drawing solid conclusions based on the point estimate of progression-free survival from single-arm studies (i.e. it should preferably be interpreted in the context of hazard ratios), we believe the heavily pretreated nature of the study population, coupled with enrolling an unselected population, warrants further investigation of FG-3246 in prostate cancer,” the analysts concluded in an April 4 note.

In FibroGen’s postmarket release yesterday, Chief Medical Officer Deyaa Adib, M.D., pointed out that the 8.7 month PFS rate related to “heavily pre-treated patients who received biologically active doses of FG-3246 in the second line or later setting prior to chemotherapy.”

“These phase 1 data provide evidence of a favorable safety profile and promising clinical activity as further evidenced by prostate-specific antigen reduction of ≥ 50% and shrinking of measurable disease,” Adib added. “We look forward to publishing the totality of the phase 1 data as we advance the program further in the clinic.”

San Francisco-based FibroGen licensed FG-3246 from Fortis Therapeutics back in May 2023 for an $80 million option fee with up to $200 million biobucks attached. The deal helped FibroGen bulk up the back end of a pipeline that had been narrowly focused around approved oral anemia drug Evrenzo and pamrevlumab.

A run of four phase 3 duds since then didn’t help improve the outlook for FibroGen’s pipeline. Evrenzo received a big clinical blow—ultimately leading AstraZeneca to end its partnership over the drug—followed by a trio of failures for pamrevlumab in non-ambulatory Duchenne muscular dystrophy and idiopathic pulmonary fibrosis.

The biotech will be hoping FG-3246 can break the run of bad luck. The ADC is also being evaluated in a phase 1/2 study for metastatic castration-resistant prostate cancer in combination with Pfizer and Astellas' Xtandi with an initial readout expected in mid-2024. FibroGen is planning to kick off a separate phase 2 trial for FG-3246 as a monotherapy in the second half of this year.