Top-line findings from Fibrogen Inc.'s phase II study and two combination safety substudies of pamrevlumab (previously FG-3019) in patients with idiopathic pulmonary fibrosis (IPF) boosted the company's partnering prospects and propelled its shares (NASDAQ:FGEN) to a historic high.

The phase II study of the anti-connective tissue growth factor (CTGF) antibody, also in development to treat pancreatic cancer and Duchenne muscular dystrophy, achieved statistical significance in the intent-to-treat population on the primary efficacy endpoint of change in forced vital capacity (FVC) percent predicted from baseline to week 48 of the study. The average decline was 2.85 in the pamrevlumab arm compared to an average decline of 7.17 in the placebo arm, or an absolute difference of 4.33.

The endpoint was measured using the random co-efficient linear regression model, similar to the methodology used by Boehringer Ingelheim GmbH (BI) in its phase III U.S. study of Ofev (nintedanib) in IPF, according to Thomas Neff, Fibrogen's founder, chairman and CEO.

"We chose this method because the published FDA clinical and statistical review, or comments, after the BI phase III made it clear that this approach is acceptable and not controversial," Neff told analysts on the company's second-quarter earnings call, which included the pamrevlumab highlights.

Patients treated with pamrevlumab had an average decrease in FVC of 129 ml at week 48 compared to an average decrease of 308 ml in patients who received placebo.

Consistent with previous studies, pamrevlumab was well-tolerated by IPF patients, with treatment-emergent adverse events (AEs) comparable in both arms of the phase II study. Three treatment-emergent serious AEs occurred in the pamrevlumab arm vs. seven in the placebo arm, according to the company.

Moreover, while IPF is known as a fatal disease, there were fewer deaths and treatment-emergent serious adverse events that led to discontinuation in the pamrevlumab arm than in the placebo arm, Elias Kouchakji, vice president of clinical development, drug safety and pharmacovigilance, explained on the company's call. He cited three deaths in the pamrevlumab arm compared to six in the placebo arm.

The double-blind, placebo-controlled portion of the phase II study randomized 103 patients on a 1-to-1 basis to pamrevlumab or placebo for 48 weeks.

The double-blind, active-controlled combination substudies randomized 57 patients to assess the safety of pamrevlumab in combination with approved IPF therapies. In one study, 36 patients on a stable dose of Esbriet (pirfenidone, Roche Holding AG) were randomized 2-to-1 to add pamrevlumab or placebo to their regimen for 24 weeks. In the second, 21 patients on a stable dose of nintedanib were randomized 2-to-1 to add pamrevlumab or placebo for 24 weeks. Pamrevlumab was well-tolerated in both studies, Fibrogen reported.

'An intriguing potential for superiority'

The San Francisco-based company is conducting additional analyses and plans to report more details next month at the European Respiratory Society (ERS) International Congress in Milan. But a phase III study, following discussions with the FDA about the regulatory pathway for pamrevlumab in IPF, is already on Fibrogen's agenda.

"We are actively considering two or three different trial designs and looking forward to talking to FDA about protocol design and getting some alignment there," Neff said.

Fibrogen's shares rocketed to an all-time high of $51.70 Tuesday before closing at $49.50 for a gain of $16.10, or 48.2 percent. More than 9.3 million shares changed hands, or about 22 times the company's three-month moving average.

Fibrogen was the biopharma darling of Wall Street in 2014, when it upsized its IPO of 8.1 million shares at $18 apiece, the high end of its range, to raise $145.8 million. Its previous high water mark was $40.59 on Jan. 6, 2015. A year ago, shares closed at just $19.47. (See BioWorld Today, Nov. 17, 2014.)

The company has money in the bank – $414.7 million as of June 30 – to run its programs. And partnering – an area where Fibrogen has shown some savvy – is also high on the company's list of priorities. The company is allied with London-based Astrazeneca plc and Astellas Pharma Inc., of Tokyo, for the development and commercialization of its lead candidate, roxadustat, an oral small molecule to treat anemia in nondialysis-dependent chronic kidney disease (CKD) and dialysis-dependent CKD patients. (See BioWorld Today, Aug. 1, 2013, and Dec. 13, 2015.)

Fibrogen's subsidiary, Fibrogen China Medical Technology Development Co. Ltd., enables the company to pursue domestic filings with the CFDA in global programs that include parallel development in the U.S., Europe and Japan. The company expects to complete the NDA submission for roxadustat in CKD anemia in China by the end of this quarter. (See BioWorld Today, Jan. 31, 2017.)

On pamrevlumab, "we will be speaking with partners in the next couple of months, so this will be a dynamic going-forward process," Neff said.

In partnering talks, Fibrogen will look for several characteristics, including a sense of urgency during negotiations and funding that meets the company's scale-up needs.

"We would not want to be waiting around for partners to provide that money where we're losing time overall," Neff said.

The other major issue, he added, is the overall business proposition.

"We believe we have the first active factor in fibrosis – antifibrotic, you can call it," Neff pointed out. "It's a huge category in medicine depending on the statistics, either the first or second or third largest killer of humans. And there's never been any therapies. So, obviously, we want a partnership that is anticipating the breadth of opportunity, both in straight fibrosis and in the cancer arena for fibrosis."

Leerink Partners LLC analyst Geoffrey Porges raised his price target on the company to $82 from $52, writing in an earnings report, "We had previously accorded little value to this program given its uncertain development history, and giving the program even a threshold phase II probability of success boosts our valuation substantially."

The mortality benefit shown in the phase II study suggests "an intriguing potential for superiority" to approved drugs, Porges suggested, noting that additional data at the ERS should continue to de-risk the program while "further opportunities and upside could emerge."

Jefferies LLC's Michael Yee also expected the bulls to run on Fibrogen's second significant pipeline success, noting that significant upside potential on the fibrosis antibody was not well-appreciated.

"Investors – or a potential global partner interested in pulmonary or orphan diseases – could go on to ascribe significant value for FG-3019 given data in hand and $2 [billion to] $4 [billion-plus] sales potential in orphan disease IPF and pancreatic cancer," Yee wrote. With positive phase II data "reasonably likely to repeat" in a phase III program based on the drug's mechanism and the totality of data, and in the context of prior IPF approvals, significant unmet need, opportunities for combination therapy, longer duration of therapy with existing products and wholly owned economics, "we think partners can ascribe $3 [billion to] $4 [billion] cap alone on this drug or around $35-50/share." With the lead roxadustat program adding even more value, Fibrogen "could be cheap compared to other orphan assets," Yee concluded.