FibroGen has convinced investors it has another potential blockbuster on its hands. Shares in the West Coast biotech shot up 60% after it posted top-line phase 2 pamrevlumab data that suggest the anti-connective tissue growth factor (CTGF) antibody can muscle in on a market fought over by Boehringer Ingelheim and Roche.
The centerpiece of the phase 2 idiopathic pulmonary fibrosis (IPF) data comes from a 103-patient trial in which participants took either pamrevlumab or placebo for 48 weeks. The study linked the drug to a 2.85 decline in forced vital capacity (FVC) % predicted, a measure of lung capacity. The average FVC % decline in the placebo cohort was 7.17, resulting in a statistically significant difference of 4.33 between the two arms.
A similar separation from placebo was seen in the assessment of FVC. The average decrease in the pamrevlumab arm was 129 ml, as compared to 308 ml in the placebo cohort.
That placebo-adjusted difference of 179 ml stands up to the data Boehringer’s Ofev and Roche’s Esbriet generated on their paths to approval. A pooled analysis of Boehringer’s two phase 3 trials linked Ofev to an improvement of about 100 ml over placebo. A one-year trial of Roche’s Esbriet linked it to a 193 ml improvement in FVC.
The data suggest pamrevlumab can hold its own in terms of efficacy. And, as the anti-CTGF drug has a different mechanism of action than Esbriet or Ofev, it could carve out a niche alongside its rivals or be used in combination with them. FibroGen laid the groundwork for combination use by testing the safety of pamrevlumab plus Esbriet or Ofev in sub-studies. But the team is yet to assess the change in FVC % predicted in the safety-focused combination trials.
A relatively clean safety profile across the combination and monotherapy trials suggests FibroGen could explore the former further. But it is yet to commit to a design for the phase 3 program, with FibroGen CEO Tom Neff only saying the team is “actively considering two or three different trial designs” on a conference call with investors.
FibroGen will move toward a final design as it analyzes the data and discusses them with the FDA. The San Francisco, CA-based biotech plans to talk to partners in parallel. But as those discussions gear up over the next couple of months, Neff wants to remain focused on keeping the program moving forward quickly.
“We would not want to be waiting around for partners to provide money where we are losing time overall,” he said.
The focus on speed will also shape FibroGen’s willingness, or lack thereof, for potential partners to participate in the phase 3 or interfere in its design.
“All these things really relate to time and getting encumbered,” Neff said.
The challenge will be to avoid delays to the advance of pamrevlumab while negotiating the sort of big, far-reaching deal envisaged by Neff. As FibroGen sees it, the phase 2 data do more than just paint pamrevlumab as a disruptor of the multibillion dollar IPF market. They position it as a possible breakthrough in a clutch of indications associated with fibrosis, including pancreatic cancer and Duchenne muscular dystrophy.
Neff wants the deal to account for this potential.
“We want a partnership that is anticipating the breadth of opportunity both in straight fibrosis and in the cancer arenas where fibrosis is important and in combination with things like the PD-L1 medicines,” he said.
Such talk has amped up expectations for pamrevlumab, which has played second fiddle to lead candidate roxadustat until now. Confirmation FibroGen has two hot properties prompted analysts at Jefferies to raise their price target from $50 to $75. And point to the $8 billion Roche paid to buy InterMune and its IPF drug to illustrate the highs FibroGen may hit.