Hopes around FibroGen’s anemia drug roxadustat were high in early 2020 when Enrique Conterno arrived as the company’s new CEO. He’d just come off a 27-year-run at Eli Lilly and was, according to an analyst interview at the time, “most impressed” by the commercial opportunity for roxadustat.But the last few years have not been kind to FibroGen and AstraZeneca's drug, with an FDA rejection, commercial disappointments and a clinical trial flop considerably blunting the oral anemia med’s trajectory.

It’s against that backdrop—plus a major layoff round—that Conterno, who's been chief at FibroGen since January 2020, is now hitting the exit.

Conterno has resigned from the FibroGen CEO post for “personal reasons,” the company said Tuesday. As FibroGen looks for a permanent successor, the company’s chief commercial officer Thane Wettig will don the mantle of interim chief executive officer. To support Wettig, Conterno plans to stick around as a special advisor to the CEO during a transition period, FibroGen added.

Conterno's departure comes just a week after FibroGen unveiled a cost-cutting plan to lay off 32% of its staff, or 104 employees, following two phase 3 flops of its potential blockbuster candidate pamrevlumab on the back of multiple setbacks with roxadustat.

“Thane has been a highly effective leader for the company over the last three years, and we have full confidence he will deliver as our Interim CEO,” Jim Schoeneck, chairman of FibroGen’s board of directors, said in a statement. Schoeneck previously served in the same interim CEO role following the untimely passing of FibroGen’s founder and long-time helmsman Thomas Neff in August 2019.

As FibroGen’s stand-in chief, Wettig said he’s looking forward to phase 3 readouts of pamrevlumab, the company’s investigational antibody against locally advanced unresectable pancreatic cancer (LAPC) and Duchenne muscular dystrophy (DMD). But analysts at William Blair saw little hope for the drug after two recent phase 3 failures.

China is where FibroGen and roxadustat have arguably seen the most success. In a Tuesday statement, Conterno spoke fondly of the company’s “rapidly growing roxadustat business in China and other territories,” while chairman Schoeneck credited the outgoing CEO with “driving both late-stage clinical execution and roxadustat commercial success in China.”

Back in late 2018, Chinese regulators were the first to approve roxadustat under the brand name Evrenzo, making it the first drug in the HIF-PHI class to score a green light anywhere. The drug was initially cleared to treat anemia from chronic kidney disease in dialysis patients and later added the non-dialysis population to its label, too.

In the first quarter of 2023, Evrenzo generated $64.1 million in China, up from $43.5 million during the same period in 2022.

Elsewhere, things haven’t gone as smoothly in Japan and Europe, where FibroGen’s partner Astellas recently booked an impairment charge worth 47 billion Japanese yen ($348 million) for Evrenzo based on gloomy sales projections.

Meanwhile, safety signals disrupted FibroGen and AZ’s plans for U.S. approval in CKD patients in 2021.

To make matters worse in the States, roxadustat in May flopped a phase 3 study in anemia patients with myelodysplastic syndromes (MDS). The trial failure has seriously jeopardized FibroGen’s U.S. partnership with AstraZeneca. MDS had been FibroGen’s salvage plan for roxadustat in the U.S. after the drug’s 2021 rejection at the FDA. Afterward, the two companies couldn’t agree on funding a new trial to support another CKD filing in the U.S.

Back when Conterno took up the FibroGen CEO post in early 2020, the company’s former chairman Tom Kearns said he was the “right individual to assume leadership of FibroGen at this pivotal time,” referring to hopes of a global launch with AstraZeneca and Astellas as its partners.

Conterno is credited with returning Lilly’s diabetes business to the industry's top spot, with annual revenue of more than $10 billion. He had originally meant to take a long “vacation” post-Lilly. But the potential for roxadustat swayed him to the FibroGen cause, former SVB Leerink analyst Geoffrey Porges wrote in a note after talking to the CEO in 2020.

It wasn’t just Conterno who was hyped on roxadustat, either. At the time, Porges’ team projected the drug could reach global sales of $3 billion to $3.5 billion by the mid-2020s. Now, those blockbuster dreams have largely faded.

Aside from roxadustat, FibroGen has also been wounded repeatedly by its would-be-blockbuster pamrevlumab. In June, the company reported that the antibody failed on the primary endpoint versus placebo in the late-stage ZEPHYRUS-1 trial of patients with idiopathic pulmonary fibrosis (IPF). That miss came just two and a half weeks after FibroGen announced pamrevlumab failed to improve function in patients with non-ambulatory Duchenne muscular dystrophy (DMD) in a phase 3 study.

That string of failures sent FibroGen back to the drawing board. The same month as pamrevlumab's twin trial flops, the company said it planned to implement "a significant cost reduction effort in the U.S." to extend its cash runway into 2026.

And in light of FibroGen's IPF failure with pamrevlumab, analysts at William Blair in a June note said they were "raising questions" on the company's future direction.

Source: bizJournals.com