The lung fibrosis pipeline thins

This month’s “win” for Pliant Therapeutics’ PLN-74809 in idiopathic pulmonary fibrosis did not convince investors, with the group’s stock closing down 1% on September 7. But Pliant is at least still in the race, which is more than can be said for several other erstwhile IPF hopefuls.

Showing efficacy in IPF has long proven tough, but it was toxicity that tripped up Galapagos’s ziritaxestat, which had been the most advanced project in development. Meanwhile, other companies appear to have quietly shelved IPF assets. With the next big readouts some way off, it will be a while until it becomes clear whether anything can stop the course of this disease.

Next up

Fibrogen’s pamrevlumab is now the one to watch, though the company’s main focus with this project is, for now, pancreatic cancer. Pamrevlumab is also in development for Duchenne muscular dystrophy.

These might seem like diverse diseases for one asset, but Fibrogen believes that by targeting connective tissue growth factor it is hitting a central node in fibrosis. The 103-patient phase 2 Praise study in IPF found that lung function, measured by forced vital capacity, declined less in pamrevlumab-treated patients versus those on placebo.

The group now needs to replicate this in its larger pivotal trials, which will be no mean feat. Like Praise, the Zephyrus studies focus on patients not currently receiving the approved IPF drugs, Roche’s Esbriet and Boehringer’s Ofev.

Roche itself has a late-stage contender, RG6354, gained through the acquisition of Promedior. In contrast, that project’s phase 3 trial does allow background therapy with Esbriet or Ofev.

And in June United Therapeutics started a late-stage IPF study of Tyvaso after seeing a positive signal in a subset of patients with IPF and pulmonary hypertension in a post-hoc analysis of the Increase study. Tyvaso was approved in March for patients with pulmonary hypertension associated with interstitial lung disease, which includes some IPF patients, but United notes that it is not authorised for IPF patients without pulmonary hypertension.

Gone quiet

Things have gone quiet for a couple of projects that looked like they would yield data imminently at the time Evaluate Vantage last carried out this analysis (Galapagos “win” highlights crowded idiopathic pulmonary fibrosis pipeline, December 4, 2020).

Kadmon’s graft-versus-host disease drug Rezurock and Novartis’s Baff receptor inhibitor ianalumab no longer appear to be in development in IPF, while Galapagos has not yet launched a promised phase 2b study of GLPG1205. That company probably has enough on its plate after its string of recent setbacks.  

Blade Therapeutics appears to have moved on from its calpain inhibitor BLD-2660, whose phase 2 trial was withdrawn owing to Covid-19. Blade now hopes to start a phase 2 IPF study next year with the autotaxin inhibitor cudetaxestat.

Still, some new projects have stepped into the pipeline, including Boehringer Ingelheim’s BI 1015550 and Astrazeneca’s saracatinib.

The table below shows a wide array of different mechanisms being tested in the lung disease. If one of these works out a lucrative market will beckon, but history suggests the odds are against these IPF hopefuls.