Incyte Celebrates 2 Trial Wins for PD-1 Drug Zynyz, Targets Anal Cancer Revival

Incyte Corporation is taking another shot at gaining approval from the FDA for its PD-1 inhibitor, Zynyz, in treating anal cancer. This follows a previous rejection by the FDA in 2021. The company announced that adding Zynyz to chemotherapy has shown significant improvements in reducing tumor progression or death in patients with untreated, inoperable, locally recurrent or metastatic squamous cell anal carcinoma (SCAC). These promising results emerged from the phase 3 POD1UM-303 trial, which met its primary endpoint. Incyte's R&D head, Pablo Cagnoni, M.D., plans to discuss these findings with the FDA to decide the next steps. If approved, Zynyz would be the first PD-1/L1 antibody approved for first-line anal cancer treatment.

Initially, SCAC was the primary target for Zynyz. However, after a negative advisory committee vote in mid-2021, the FDA rejected the drug, leading Incyte to focus on other indications. Zynyz eventually received its first U.S. approval for treating Merkel cell carcinoma last year, while the company continued to pursue the POD1UM-303 trial for first-line anal cancer.

In another development, Incyte announced that Zynyz, when combined with chemotherapy, also showed better outcomes compared to chemotherapy alone in patients with first-line metastatic non-small cell lung cancer (NSCLC) in the phase 3 POD1UM-304 trial. These lung cancer results will also be part of Incyte’s discussions with the FDA. However, it remains uncertain whether the FDA will accept these data for filing approvals.

During an advisory committee meeting concerning Zynyz’s initial application for second-line anal cancer, several issues were raised, including a high number of deaths unrelated to disease progression and a low tumor response rate. These concerns might lead the FDA to request overall survival data for first-line treatment settings. The first-line NSCLC indication is particularly competitive, with Merck’s Keytruda being the established standard of care. Thus, the FDA may question the validity of using chemotherapy as a comparator in the phase 3 trial.

The use of an outdated comparator arm was a reason behind the FDA's rejection of Innovent Biologics' PD-1 drug Tyvyt in March 2022 for first-line nonsquamous NSCLC. Incyte, however, has expressed confidence in the design and clinical sites of the POD1UM-304 trial. Conducted across the Americas, Europe, and Asia, the trial included a diverse population, which Incyte believes strengthens the study's validity.

Nevertheless, diversity alone may not address the issue of a weak comparator arm. Only a few months after Tyvyt's rejection, the FDA approved Regeneron’s Libtayo and chemotherapy for newly diagnosed NSCLC based on a trial that also used chemotherapy as the control arm. However, that trial started before Keytruda received first-line approvals in 2018, whereas Zynyz’s trial began in late 2020. With only three of its 141 locations in the U.S., it could indicate a lack of interest in enrolling patients for chemotherapy alone when there's an established PD-1 standard of care.

Incyte has also announced a significant retreat from the immuno-oncology sector, stopping further development of its oral PD-L1 inhibitors and two separate antibodies targeting LAG-3 and TIM-3, among others. This decision is attributed to the competitive landscape and internal pipeline evolution. Despite this, Incyte remains commercially focused on its products Jakafi and Opzelura.

Jakafi's revenue grew by 3% year over year to $706 million in the second quarter, exceeding Wall Street’s expectations. Total demand from paying patients increased by 9%. Opzelura also showed strong performance, with a 9% increase above the consensus, bringing in $122 million for the quarter. Incyte’s total quarterly revenues exceeded $1 billion, and the company updated its full-year revenue guidance to a range of $2.71 billion to $2.75 billion. An FDA decision on its anti-CSF-1R antibody axatilimab for third-line chronic graft-versus-host disease is expected in August.

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