MorphoSys AG, Planegg, Germany, announced compelling results from the Phase 3 MANIFEST-2 study evaluating pelabresib, a BET inhibitor in clinical development, in combination with the JAK inhibitor ruxolitinib versus placebo plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis.
Myelofibrosis is a form of blood cancer that is difficult to treat and is characterized by bone marrow fibrosis, an enlarged spleen and anaemia and often requires regular blood transfusions. The disease leads to considerable physical symptoms such as fatigue, night sweats and pain, which severely impair the quality of life of those affected. Current therapeutic approaches with JAK inhibitors improve individual symptoms but do not address all aspects of myelofibrosis, and only about half of patients achieve adequate symptom control. There is therefore an urgent need for new and more effective treatment options for myelofibrosis patients.
The MANIFEST-2 study met its primary endpoint with the combination therapy demonstrating a statistically significant and clinically meaningful improvement in the proportion of patients achieving at least a 35% reduction in spleen volume at week 24 (SVR35 response rate of 66% versus 35%).
The key secondary endpoints assessing symptom improvement showed a strong positive trend in favor of the combination of pelabresib and ruxolitinib, particularly in intermediate-risk patients. Symptom reduction, as measured by the Total Symptom Score (TSS), was significant for both the overall patient population and the intermediate risk group.
Pelabresib plus ruxolitinib also showed a clinically meaningful improvement in anemia compared to placebo and ruxolitinib.
Tolerability data were consistent with previous clinical trials, with no new safety signals.
“We are very pleased with this positive outcome. Pelabresib in combination with ruxolitinib demonstrated strong reductions in spleen volume and symptoms over ruxolitinib monotherapy – the most impressive benefits seen in clinical studies of patients with myelofibrosis,” said Jean-Paul Kress, M.D., Chief Executive Officer of MorphoSys. “Importantly, we saw significant symptom improvements for the vast majority of patients in the study."
MorphoSys intends to submit the results of this study for regulatory approval in the US and Europe in mid-2024.
The detailed results of the MANIFEST-2 study will be presented at the 65th Annual Meeting of the American Society for Hematology (ASH) in December.