Galapagos's decision this week to push on with GLPG1205 in idiopathic pulmonary fibrosis puts another novel mechanism into later-stage trials for the fatal lung condition. New data on the project were not all positive, however, and the jury will remain out on its prospects for now.
Although the company claimed a win in the phase II Pinta study, GLPG1205 did not show a statistically significant improvement over placebo in forced vital capacity, the primary endpoint. Galapagos pointed out that the trial had not been powered to show significance, but tolerability issues with GLPG1205 plus the approved IPF drug Ofev raise another red flag.
In the 68-patient Pinta trial, patients were given GLPG1205 on top of either Boehringer's Ofev or Roche's Esbriet, the two currently approved IPF drugs. At 26 weeks, patients in the treatments groups showed a 34ml decline in forced vital capacity, versus a 76ml decline in the placebo group.
At least the company is not rushing into phase III – a phase IIb dose-finding trial will be the next step. Galapagos itself has other shots on goal, with several assets in the crowded mid-stage pipeline. Still, IPF has proven a very difficult disease to treat, and the failure rate is likely to be high among these projects.
Bristol Myers Squibb is another company that seems determined to conquer the space, and with several phase II trials underway. The big pharma company will be hoping to add to the late-stage pipeline itself in the coming years.
Phase III contenders
Three novel IPF projects are in phase III, according to EvaluatePharma; of these, Galapagos’s autotaxin inhibitor ziritaxestat, which is partnered with Gilead, looks set to be the first to yield phase III data.
Galapagos will hope to replicate promising data seen in the phase II Flora trial, although this recruited just 23 patients. At present, ziritaxestat is attracting the biggest sellside forecasts: consensus puts 2026 sales in IPF at $726m.
Fibrogen’s pamrevlumab is also in late-stage development; enrolment into the pivotal Zephyrus study was paused for two months this year because of the Covid-19 pandemic, but is now up and running again.
And Roche’s acquisition of Promedior last year provided a vote of confidence in PRM-151, a recombinant form of human pentraxin-2 now known as RG6354, which Roche has since taken into phase III.
Roche already has the approved IPF therapy Esbriet; however, neither this compound nor Boehringer’s Ofev are considered disease modifying, so there is plenty of room for improvement.
Bristol’s fibrosis push
This goes some way towards explaining the huge interest in IPF. Of all the companies vying for a piece of this market, Bristol has more bets than most.
In mid-stage development it has the JNK1 inhibitor CC-90001, gained through the acquisition of Celgene, and the LPA1 antagonist BMS-986278.
The group also has another LPA1 antagonist, BMS-986337, in phase I, and an option over Nitto Denko’s ND-L02-s0201 in IPF; the latter is a small interfering RNA targeting heat shock protein 47.
Galapagos is perhaps the only group to rival Bristol in the number of assets it has in development for IPF. As well as the aforementioned projects, Galapagos is evaluating GLPG4716, a phase II-ready chitinase inhibitor. It also has GLPG4124 and GLPG4586, currently at the preclinical stage.
|Selected IPF projects in mid to late-stage development|
|Ziritaxestat (GLPG1690)||Galapagos/ Gilead||Autotaxin inhibitor||Isabela1 (NCT03711162), Isabela2 (NCT03733444), both end Dec 2021|
|Pamrevlumab||Fibrogen||Anti-CTGF antibody||Zephyrus (NCT03955146) ends Dec 2022; Zephyrus II (NCT04419558) ends Apr 2023|
|RG6354 (PRM-151/pentraxin-2)||Roche||MREG differentiation stimulant||NCT04552899, ends Feb 2023|
|GLPG1205||Galapagos||GPR84 antagonist||Pinta (NCT03725852) reported, ph2b dose-finding study planned|
|Belumosudil (KD025)||Kadmon||ROCK2 inhibitor||NCT02688647 completed Jul 2020|
|MN-001||Medicinova||Leukotriene, PDE 3 & 4 & 5-LO inhibitor||NCT02503657, ends Dec 2020|
|Ifenprodil (NP-120)||Algernon||NMDA2B antagonist||NCT04318704, ends Mar 2021|
|CC-90001||Bristol Myers Squibb||JNK1 inhibitor||NCT03142191, ends Jun 2021|
|ND-L02-s0201 (BMS-986263)*||Nitto Denko||HSP47 RNAi therapeutic||Juniper (NCT03538301), ends Jul 2021|
|Jaktinib||Suzhou Zelgen Biopharmaceuticals||Jak 1-3 inhibitor||NCT04312594, ends Oct 2021|
|TD139||Galecto Biotech||Galectin-3 inhibitor||Galactic-1 (NCT03832946), ends Dec 2021|
|PLN-74809||Pliant Therapeutics||TGF beta 1 inhibitor||NCT04396756, ends Dec 2021|
|VP01 (C21)||Vicore Pharma||AT2 agonist||NCT04533022, ends Mar 2022|
|Ianalumab (VAY736)||Novartis||Anti-BAFF antibody||NCT03287414, ends Aug 2022|
|Setanaxib (GKT831)||Genkyotex||NOX1 & 4 inhibitor||NCT03865927, ends Jul 2023|
|BMS-986278||Bristol Myers Squibb||LPA1 antagonist||NCT04308681, ends Nov 2023|
|BLD-2660||Blade Therapeutics||Calpain inhibitor||NCT04244825, suspended due to Covid-19|
|*Bristol Myers Squibb has licensed project in liver diseases, and has option in IPF. Source: EvaluatePharma & clinicaltrials.gov.|