Momelotinib Dihydrochloride

Incyte will bring its latest PD-1 data in anal cancer and lung cancer to the FDA, but whether the agency will accept them for evaluation remains to be seen. Incyte is gunning for a first-in-class nod for PD-1 inhibitor Zynyz in anal cancer again after being turned away by the FDA in 2021.The addition of Zynyz to chemotherapy significantly reduced the risk of tumor progression or death in patients with previously untreated, inoperable locally recurrent or metastatic squamous cell anal carcinoma (SCAC), Incyte announced Tuesday alongside its second-quarter financial results.The phase 3 POD1UM-303 trial therefore met its primary endpoint, and Incyte plans to discuss the results with the FDA to determine next steps, Incyte’s R&D head, Pablo Cagnoni, M.D., told investors on a call Tuesday. If approved, Zynyz could become the first PD-1/L1 antibody approved for first-line anal cancer, he said.SCAC was the first indication Incyte originally had planned for Zynyz. But after a negative advisory committee vote in the summer of 2021, the FDA rejected the PD-1 inhibitor. Incyte then changed course and won Zynyz’s initial U.S. nod in Merkel cell carcinoma last year, while in parallel running the randomized POD1UM-303 trial in first-line anal cancer.Separately, Incyte on Tuesday said Zynyz’s combination with chemotherapy also outperformed chemo alone in extending the lives of patients with first-line metastatic non-small cell lung cancer in the phase 3 POD1UM-304 trial.The lung cancer results will also be part of Incyte’s discussions with the FDA. But in both cases, uncertainties lie in whether the Delaware company can file for approvals. During an advisory committee meeting about Zynyz’s original second-line anal cancer application, a relatively high number of deaths not related to disease progression were raised as a concern—in addition to a low tumor response rate and a lack of durability data. This prior record of nonrelapse deaths might prompt the FDA to ask for overall survival data in the first-line setting.As for first-line NSCLC, the indication is the largest for the PD-1/L1 drug class. However, Merck’s Keytruda has long established itself as the standard of care here. So, whether the FDA will accept a phase 3 trial that used chemotherapy as a comparator arm remains a big question.An outdated comparator arm was one reason why the FDA in March 2022 snubbed Innovent Biologics’ then-Eli Lilly-partnered PD-1 drug Tyvyt in first-line nonsquamous NSCLC. The fact that the pivotal trial supporting that application was conducted solely in China—which explained the weak control arm—was a key reason for that rejection.Incyte, for its part, has previously voiced confidence about the POD1UM-304 trial’s design and clinical sites. During a May 2022 conference call following Tyvyt’s setback, Incyte’s Chief Medical Officer Steven Stein, M.D., noted that Zynyz’s trial was “in a completely different position” from Tyvyt “given the diversity of our population across the world, the size of the study, [and] replication of the statistics to achieve the same endpoints [as Keytruda].”POD1UM-304 was conducted across the Americas, Europe and Asia. However, diversity alone can’t negate the weak comparator problem.A few months after Tyvyt’s rejection, the FDA in November 2022 approved Regeneron’s Libtayo and chemo in newly diagnosed NSCLC based on a phase 3 trial that also used chemo as the control arm. But that Regeneron study, coded EMPOWER-Lung 3, was initiated in early 2018 before Keytruda’s first-line approvals in squamous and nonsquamous NSCLC later that year.In contrast, Zynyz’s POD1UM-304 was launched two years later in the fall of 2020. Among the trial’s 141 locations, only three are in the U.S., which could suggest investigators’ reluctance toward enrolling patients to receive chemo alone when there’s a PD-1 standard of care available.The two positive Zynyz readouts came as Incyte on Tuesday telegraphed a massive retreat in the immuno-oncology field by ending further development of its oral PD-L1 inhibitors and two separate antibodies targeting LAG-3 and TIM-3, plus a LAG-3xPD-1 bispecific. The company cited the competitive landscape and evolution of its internal pipeline as the reasons for the discontinuation. Meanwhile, the commercial focus at Incyte remains on Jakafi and its sister topical med Opzelura.Despite competition from GSK’s Ojjaara, Jakafi’s revenue increased by 3% year over year to $706 million during the second quarter, beating Wall Street’s expectations of $677 million. Total demand from paying patients—versus free drugs—grew 9% year over year.As for Opzelura, the cream’s $122 million haul during the quarter—including $11 million from Europe—also came 9% above the Street’s consensus. New U.S. patient starts across atopic dermatitis and vitiligo as well as launches in Germany and France, were cited as growth drivers.All told, Incyte’s total quarterly revenues surpassed the $1 billion mark, reaching $1.04 billion in the second quarter. The company raised the lower end of its full-year guidance to a new range of $2.71 billion to $2.75 billion. An FDA decision on its anti-CSF-1R antibody axatilimab in third-line chronic graft-versus-host disease is expected in August. 

The new single-dose medicine prevents the relapse of Plasmodium vivax malaria. Credit: sun ok / Shutterstock. GSK and Medicines for Malaria Venture (MMV) have announced the launch of a new single-dose medicine, tafenoquine, to prevent the relapse of Plasmodium vivax (P. vivax) malaria in malaria-endemic countries Brazil and Thailand. Tafenoquine is co-administered with chloroquine, for radical cure. An antimalarial drug, tafenoquine is an 8-aminoquinoline that targets the liver stage of P. vivax malaria. When used with chloroquine, which addresses the blood-stage infection, tafenoquine can effectively treat both stages of the disease. But tafenoquine can cause acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. See Also: Ascentage Pharma’s olverembatinib approved in Macau for leukaemia NN-6561 by Novo Nordisk for Metabolic Dysfunction-Associated Steatohepatitis (MASH): Likelihood of Approval As a result, a G6PD test is essential before the drug can be prescribed. The Ministries of Health in Thailand and Brazil have conducted feasibility studies on the routine use of tafenoquine after point-of-care G6PD testing. These studies, supported by MMV, have been instrumental in their decisions to adopt this new anti-malarial strategy. In Brazil, the urgency of the public health emergency in the Yanomami Special Indigenous Health District, where P. vivax malaria is particularly prevalent, led to the accelerated approval of tafenoquine in March 2024. Tafenoquine has now received approvals in Australia, Brazil, Colombia, Ethiopia, Guyana, Peru, the Philippines and the US. GSK chief global health officer Thomas Breuer stated: “The news underscores GSK’s long-standing commitment to malaria and we are proud that tafenoquine, co-administered with chloroquine, the first radical cure medicine for P. vivax malaria, is now launched in both Brazil and Thailand, taking us another step closer to our shared goal of eliminating malaria. “Working together with MMV and PATH [the Program for Appropriate Techonology in Health] through the Partnership for Vivax Elimination to optimise this new treatment option has been fundamental to countries being able to introduce this new tool.” In June 2024 GSK received approval from Japan’s Ministry of Health, Labour and Welfare (MHLW) for Omjjara (momelotinib) to treat patients with myelofibrosis.