MorphoSys Forges Ahead Despite Mixed Phase III Myelofibrosis Trial Results

Pictured: Four people with their thumbs up in approval/iStock, PeopleImages

Pictured: Four people with their thumbs up in approval/iStock, PeopleImages

MorphoSys is moving ahead with its investigational BET inhibitor pelabresib, a Phase III myelofibrosis drug candidate, even though it failed to meet one of two key endpoints in a recent trial.

The biopharma’s decision to stick with pelabresib follows similarly mixed results for AbbVie’s myelofibrosis drug navitoclax that prompted MorphoSys CEO Jean-Paul Kress at the time to call its competitor’s Phase III showing a “failed” trial after missing one of two endpoints.

Topline results announced Monday for the Phase III MANIFEST-2 study of pelabresib in combination with ruxolitinib found that it met its key primary endpoint of “statistically significant and clinically meaningful improvement in the proportion of patients achieving at least a 35% reduction in spleen volume” by 24 weeks. In total, 66% of patients hit this endpoint, which is the “the best prognostic indicator we have at our disposal for long-term myelofibrosis patient outcomes,” John Mascarenhas, director of the Adult Leukemia Program at The Tisch Cancer Institute, said in a statement.

However, the drug combo failed to demonstrate a sufficient improvement in total symptom score to hit its second key secondary endpoint: 52% of patients taking pelabresib and ruxolitinib saw at least a 50% reduction in total symptom score, compared to 46% of patients on a placebo and ruxolitinib.

Ruben Mesa, executive director of the Atrium Health Levine Cancer Center and Atrium Health Wake Forest Baptist Comprehensive Cancer Center, said in a statement that the symptom reduction demonstrated “an important result that should be strongly considered when evaluating the efficacy of the pelabresib and ruxolitinib combination therapy for myelofibrosis.”

The announcement also noted that “a greater proportion of patients achieved hemoglobin response” than those receiving placebo, and that “the safety of pelabresib and ruxolitinib was consistent with the previously observed safety profile of this combination therapy” with fewer patients suffering anemia versus placebo.

The endpoint has been of particular interest to analysts over the last few months of investor calls, after AbbVie’s navitoclax, a rival drug to pelabresib, failed to meet that endpoint. Kress told investors in September 2023 that AbbVie definitively “failed their Phase III trial.”

However, in a statement, Kress said the company is “very pleased” with its own “positive” outcome, adding that MorphoSys saw “significant symptom improvements for the vast majority of patients in the study.”

MorphoSys is looking to submit a New Drug Application for pelabresib in combination with ruxolitinib in myelofibrosis to the FDA and a Marketing Authorization Application to the European Medicines Agency in the middle of 2024.

The combination treatment received a Fast Track designation from the FDA in 2018.

MorphoSys first brought pelabresib under its umbrella back in 2021, when it acquired Consellation Pharmaceuticals for $1.7 billion. Pelabresib was one of the company’s two lead product candidates, the other being CPI-0209, a second-generation EZ2H inhibitor. Kress said at the time the acquisition “represents a major step forward for MorphoSys as we bolster our position in hematology-oncology.”

Connor Lynch is a freelance writer based in Ottawa, Canada. Reach him at

Back to news