The lung fibrosis pipeline thins
This month Pliant Therapeutics claimed a win in idiopathic pulmonary fibrosis, but other projects have fallen by the wayside.
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.
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.
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.
|Still in the mid-to-late stage pipeline…|
|Pamrevlumab||Fibrogen||Anti-CTGF antibody||Zephyrus-I top-line data due mid-2023; Zephyrus-II ends Apr 2023|
|RG6354 (PRM-151, pentraxin-2)||Roche||MREG differentiation stimulant||Starscape ends Feb 2023|
|Tyvaso||United Therapeutics||Prostacyclin mimetic||Teton ends Jun 2024|
|PLN-74809||Pliant Therapeutics||αvß6 and αvß1 integrin inhibitor||NCT04396756 ends Mar 2022, 12-pt PET trial reported Sep 2021|
|GLPG1205||Galapagos||GPR84 antagonist||Claimed win in Pinta no active trials since 2020|
|Ifenprodil (NP-120)||Algernon Pharmaceuticals||NMDA2B antagonist||NCT04318704 ended Aug 2021|
|Jaktinib||Suzhou Zelgen Biopharmaceuticals||Jak 1-3 inhibitor||NCT04312594 ends Oct 2021|
|BI 1015550||Boehringer Ingelheim||Phosphodiesterase 4 inhibitor||NCT04419506 ends Oct 2021|
|ND-L02-s0201 (BMS-986263)*||Nitto Denko||HSP47 RNAi therapeutic||Juniper ends Aug 2022|
|CC-90001||Bristol Myers Squibb||JNK1 inhibitor||NCT03142191 ends Sep 2022|
|Saracatinib||Astrazeneca||Src kinase inhibitor||Ph1/2 Stop-IPF** ends Sep 2022|
|GB0139 (TD139)||Galecto Biotech||Galectin-3 inhibitor||Galactic-1 ends Dec 2022|
|VP01||Vicore Pharma||AT2 agonist||Air ends Dec 2022|
|BMS-986278||Bristol Myers Squibb||LPA1 antagonist||NCT04308681 ends May 2023|
|Setanaxib (GKT831)||Calliditas/Genkyotex||NOX1 & 4 inhibitor||NCT03865927** ends Jul 2023|
|Fallen by the wayside…|
|Ziritaxestat (GLPG1690)||Galapagos/Gilead||Autotaxin inhibitor||Isabela1, Isabela2, stopped on toxicity signal Feb 2021|
|Rezurock (belumosudil, KD025)||Sanofi/Kadmon||Rock2 inhibitor||Ph2 (NCT02688647) ended Jul 2020; focus on GvHD & systemic sclerosis|
|Ianalumab (VAY736)||Novartis||Anti-Baff antibody||Ph2 (NCT03287414) ended Dec 2020, focus on SLE, AIH, Sjogren's syndrome|
|Tipelukast (MN-001)||Medicinova||Leukotriene, PDE 3 & 4 & 5-LO inhibitor||15-pt ph2 IPF trial failed, development continues in Nash|
|Fezagepras (PBI-4050)||Liminal Biosciences||GPR40 agonist & GPR84 antagonist||Company halted plans for ph2b trial planned in IPF in H2 2021|
|BLD-2660||Blade Therapeutics||Calpain inhibitor||NCT04244825, withdrawn due to Covid-19|
|*Bristol Myers Squibb has licensed project in liver diseases, and has option in IPF. **investigator-sponsored trial. AIH=autoimmune hepatitis; GvHD= graft vs host disease; SLE=systemic lupus erythematosus. Source: EvaluatePharma, clinicaltrials.gov.|