Incyte Discontinues BET Inhibitor Program Amid Industry-Wide Safety Concerns

Incyte Corporation has announced the discontinuation of its BET inhibitor program, marking a significant shift in the company's research and development priorities. This decision comes against a backdrop of growing safety concerns surrounding the BET inhibitor drug class across the pharmaceutical industry.

BET Inhibitor Program Halted

Incyte revealed in its third-quarter earnings report that it has paused development of INCB57643, a BET inhibitor that was being evaluated in a phase 2 myelofibrosis study in combination with the company's blockbuster drug Jakafi. The company attributed this move to "ongoing pipeline prioritization efforts" rather than explicitly citing safety concerns.

However, industry analysts at William Blair noted that they were "not surprised by the program's discontinuation due to safety concerns for the class." The BET inhibitor had been slated to enter a phase 3 study for myelofibrosis this year, but those plans have now been shelved.

Broader Industry Challenges for BET Inhibitors

Incyte's decision follows a series of setbacks for BET inhibitors across the pharmaceutical sector. In 2024, Novartis faced a significant challenge when it detected an imbalance in the rate of acute myeloid leukemia in a phase 3 study of its myelofibrosis drug pelabresib, a BET inhibitor acquired through its MorphoSys buyout. This discovery led to a delay in Novartis's approval plans and resulted in an $800 million impairment in the company's finances.

Further highlighting the challenges faced by this drug class, the FDA placed a clinical hold on a phase 1b plaque psoriasis study of Vyne Therapeutics' BET inhibitor earlier this year. This action was taken after reports of testicular toxicity in dogs from a separate, nonclinical test.

Incyte's Pipeline Adjustments

In addition to halting the BET inhibitor program, Incyte announced other changes to its development pipeline:

1. The company is discontinuing work on INCA034460, an anti-CD122 drug that was being assessed in a phase 1 study for vitiligo.

2. Development of povorcitinib, a JAK1 inhibitor, will no longer continue for chronic spontaneous urticaria (CSU). However, Incyte still plans to submit the drug for approval to European regulators as a treatment for moderate to severe hidradenitis suppurativa (HS) before the end of 2025, with an FDA application to follow in early 2026.

Despite these setbacks, Incyte maintains a strong portfolio of approved medications, including the fast-growing JAK cream Opzelura, lymphoma treatment Monjuvi, and PD-1 inhibitor Zynyz, alongside its flagship product Jakafi.