Lynk Pharmaceuticals reports sustained zemprocitinib responses through week 76 in Phase III COURAGE-RA, with efficacy and long-term safety limitations.
Written By: Charvi Kalal, PharmD
Reviewed By: Pharmacally Editorial Team
Lynk Pharmaceuticals reported positive long-term results from its Phase III COURAGE-RA trial of zemprocitinib in adults with moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARDs).
Announced on October 28, 2026, the findings showed sustained clinical responses through week 76 with the investigational oral Janus kinase 1 (JAK1) inhibitor. The study met its primary and key secondary endpoints at week 24, with statistically significant improvements over placebo (p<0.0001).
COURAGE-RA Study Design
The randomized, double-blind, placebo-controlled trial (NCT06276998) enrolled 430 patients, of whom 429 received at least one dose of study treatment. During the initial 24 weeks, participants received zemprocitinib 12 mg twice daily or placebo. After week 24, patients continued or switched to active treatment, with efficacy and safety assessed through week 76, followed by a four-week safety follow-up.
The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 24. Key secondary endpoints included ACR50 response and a Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) of 3.2 or less. Secondary reporting of the week-24 findings cited ACR20 responses of 79.1% with zemprocitinib and 39.7% with placebo.
Clinical Responses Maintained Through Week 76
Among patients who continued zemprocitinib, ACR20, ACR50 and ACR70 response rates were 93.0%, 79.9% and 52.5%, respectively, at week 52. At week 76, the corresponding rates were 91.8%, 80.5% and 62.4%.
Measures of disease activity also remained favorable. At weeks 52 and 76, respectively, 85.5% and 81.4% of continuously treated patients achieved low disease activity, defined as DAS28-CRP of 3.2 or less. Using the Clinical Disease Activity Index (CDAI), 81.5% and 81.0% achieved scores of 10 or less.
Improvements in physical function were reported in 84.5% of patients at week 52 and 86.7% at week 76, measured as an improvement of at least 0.22 points in the Health Assessment Questionnaire Disability Index (HAQ-DI) from baseline.
Patients who switched from placebo to zemprocitinib at week 24 also showed clinical responses by week 76. Their ACR20, ACR50 and ACR70 response rates were 92.0%, 77.6% and 55.1%, respectively.
Together, these findings indicate that clinical responses were maintained during extended treatment in the reported populations. However, the increase in ACR70 from week 52 to week 76 should not automatically be interpreted as continued improvement in every patient. The announcement does not provide the numbers analyzed at each time point, treatment discontinuation rates or details of missing-data handling.
Long-Term Safety Findings
Lynk reported that zemprocitinib’s safety profile was generally comparable to placebo during the initial 24-week period and remained consistent through week 76, with no new safety signals identified.
The company also reported an increase in mean hemoglobin levels, rare grade 3 or 4 alanine aminotransferase (ALT) elevations, rare grade 3 aspartate aminotransferase (AST) elevations and no grade 4 AST elevations.
These findings provide preliminary information on longer-term tolerability but do not establish a safety advantage over other treatments. The announcement does not provide detailed event rates for serious infections, herpes zoster, venous thromboembolism, major cardiovascular events, malignancy or adverse-event-related discontinuations. Such data are important for a fuller assessment of a JAK inhibitor’s benefit-risk profile.
Development and Regulatory Context
Zemprocitinib remains investigational for RA. Lynk is also developing the drug for atopic dermatitis and ankylosing spondylitis. The company has reported that China’s National Medical Products Administration accepted a new drug application for atopic dermatitis, while its Phase III ankylosing spondylitis programme is ongoing. Simcere Pharmaceutical Group is Lynk’s commercialization partner for zemprocitinib in Greater China.
The long-term RA announcement does not establish an approval decision or provide a detailed regulatory timeline for this indication.
Clinical Interpretation
The COURAGE-RA results support the continued evaluation of zemprocitinib in patients with bDMARD-inadequate response RA, demonstrated by sustained ACR responses and low disease activity through Week 76, alongside confirmed clinical activity in placebo-crossover patients. However, interpretation remains limited by the long-term phase’s lack of a concurrent placebo control, incomplete safety and population reporting, and an absence of comparative data against other JAK inhibitors or efficacy in prior JAK-failure populations. Consequently, full peer-reviewed publication of safety, efficacy, and discontinuation data is required to establish its benefit-risk profile, and zemprocitinib should remain classified as an investigational treatment.
Reference
Lynk Pharmaceuticals Reports Positive Long-Term Phase III Results for Zemprocitinib in bDMARDs-Inadequate Responders with Moderate-to-Severe Rheumatoid Arthritis, Lynk Pharmaceuticals, 27 October 2026
A Study of LNK01001 Capsule in Subjects with Active Rheumatoid Arthritis (COURAGE-RA), ClinicalTrials.gov ID NCT06276998
About the Writer
Charvi Kalal (LinkedIn) is a Pharm.D intern and aspiring medical writer with hands-on experience in medical writing, clinical research, pharmacovigilance, and clinical pharmacy. She has experience in medical content writing through CliMed, along with exposure to ADR monitoring, prescription analysis, patient counselling, literature review, and research documentation. Her research focuses on ADR monitoring and reporting in breast cancer patients receiving targeted therapy. With certifications in GCP, biomedical research, scientific writing, and clinical research, she is passionate about transforming scientific evidence into accurate, engaging, and accessible healthcare content.