A phase 3 rheumatoid arthritis trial of Lynk Pharmaceuticals’ JAK1 inhibitor in China has hit its primary endpoint, boosting the prospects of a candidate designed to avoid the adverse events caused by existing drugs.
JAK1 inhibitors such as AbbVie’s Rinvoq have improved outcomes in rheumatoid arthritis and a range of other indications, racking up blockbuster sales in the process. But the drug mechanism is associated with safety and tolerability problems—including increased risk of infection, cardiovascular events and death—that have led the FDA to slap boxed warnings on product labels.
Lynk designed zemprocitinib, also called LNK01001, to have higher selectivity and better safety than the existing options. The biotech put its hypothesis to the test in a phase 3 trial that compared zemprocitinib to placebo in patients with moderate to severe active rheumatoid arthritis in China.
After 24 weeks of twice-daily oral dosing, 79.1% of people taking zemprocitinib met the ACR20 criteria, indicating they had at least a 20% improvement on a composite measure of disease severity. With 39.7% of people on placebo meeting the criteria, the study achieved its primary endpoint.
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Lynk reported a significant difference in ACR20 at Week 12, and in ACR50—which requires at least a 50% improvement on the composite measure—at weeks 12 and 24. Significant improvements in DAS28, a measure of disease severity, rounded out the dataset.
The availability of other JAK1 inhibitors means zemprocitinib will face tougher competitors than placebo when physicians evaluate whether to use the molecule in the real world. With the study lacking an active control arm, and cross-trial comparisons being potentially unreliable, it is unclear exactly how Lynk’s candidate is shaping up versus the competition. But the available data suggest the asset has promise.
Lynk enrolled patients on a stable dose of conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs). An inadequate response or intolerance to biologic DMARDs was an enrollment requirement. AbbVie reported (PDF) an ACR20 of 65% for Rinvoq at Week 12 in a phase 3 trial that gave background DMARDs to patients failed by biologics.
In Lynk’s trial, most treatment-emergent adverse events were mild to moderate in severity, and the incidence of serious adverse events was comparable between the zemprocitinib and placebo groups. The biotech saw no new safety signals.
Earlier trials reported no major adverse cardiovascular events, blood clots, serious infections or formations of malignant tumors, a set of safety issues linked to Rinvoq.
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Simcere partnered with Lynk to commercialize zemprocitinib in greater China in 2022. When Lynk filed (PDF) to go public in Hong Kong last November, the company said it planned to file for approval in rheumatoid arthritis in the second half of 2026. A filing for approval in atopic dermatitis, an indication not covered by the deal with Simcere, is planned for the first half of the year.
Lynk has the rights to all indications outside China. The biotech offloaded the ex-China rights to another asset, an allosteric TYK2 inhibitor, to Formation Bio last month in a deal worth more than $600 million in biobucks.
