On February 10, Gilead and Galapagos announced the discontinuation of the ISABELA Phase III clinical trials investigating ziritaxestat, a once-daily autotaxin inhibitor formerly known as GLPG-1690, in patients with idiopathic pulmonary fibrosis (IPF). This decision follows the recommendations of an Independent Data Monitoring Committee (IDMC), which concluded that ziritaxestat’s risk-benefit profile no longer supports its use in the IPF trials. The companies also announced that it would discontinue all ziritaxestat studies, including the Phase IIa NOVESA trial in systemic sclerosis. Due to IPF’s high clinical unmet needs, this discontinuation represents a major setback in the disease space, since ziritaxestat was expected to be the first late-state pipeline product to launch for IPF in the next several years.
IPF clinical trial design has historically been difficult for drug manufacturers to navigate. Key opinion leaders (KOLs) interviewed by GlobalData noted that there are significant challenges in designing appropriate trials, such as selection of patient populations and appropriate endpoints. High prescribing physicians will be closely scrutinizing trial data, which was likely instrumental in the implementation of a Gilead and Galapagos IDMC. KOLs were initially very optimistic about the design of the ISABELA trials, if successful. However, some KOLs did express reservations about the agent’s future, since its Phase II FLORA study only tested 23 patients total. Ziritaxestat was expected to launch in 2023 and garner $557.6M in sales by 2029 in the seven major markets (7MM: US, France, Germany, Italy, Spain, UK, and Japan). Ziritaxestat’s departure clears the way for Roche’s pamrevlumab, the next pipeline agent expected to launch for IPF and a KOL favorite based on available data.
Although this is undoubtedly a significant setback both for Gilead and Galapagos, Galapagos does have another pipeline agent in development. In November 2020, Galapagos announced positive topline results for its Phase IIA randomized PINTA study of GLPG1205. However, due to the expected trials needed to gain approval (a Phase IIB dose ranging study and at least two pivotal Phase III studies), it is unlikely that this drug will launch prior to 2029. By the time of its launch, GlobalData assumes that GLPG1205 will have competition from up to seven marketed agents and two generics, compared to just the two marketed agents that ziritaxestat was set to join in 2023.