MorphoSys shrugs off mixed results for myelofibrosis drug


MorphoSys has said it will press ahead with regulatory filings for its myelofibrosis drug candidate pelabresib, despite mixed results in a phase 3 trial.

The German biotech says it hopes the totality of data for the BET inhibitor in a population of JAK inhibitor-naïve myelofibrosis patients will be enough to convince regulators to back the drug, although, investors were spooked by the announcement and its shares were trading down around 24% at the time of writing.

The update from the MANIFEST-2 study showed that adding pelabresib to therapy with Novartis/Incyte's JAK inhibitor Jakafi (ruxolitinib) – a standard first-line therapy for the chronic blood cancer – achieved the primary objective of a statistically significant improvement in the proportion of patients with a 35% or greater reduction in spleen volume after 24 weeks’ treatment, almost doubling it to 66% from 35% for Jakafi plus placebo.

However, MorphoSys’ drug was unable to achieve the key secondary objective of reducing symptoms of myelofibrosis, a rare type of blood cancer that causes scar tissue to form in the bone marrow and leads to anaemia, fatigue, itching, weight loss, and other symptoms.

The proportion of patients achieving a 50% reduction in total symptom score, as well as the absolute reduction in symptoms score, was not significantly different between the groups, although, MorphoSys said there was a “strong positive trend” in favour of the pelabresib group.

“I believe MANIFEST-2 provides us with valuable evidence that the addition of pelabresib offers meaningful improvements over JAK inhibitor monotherapy as a first-line approach for patients with myelofibrosis,” said John Mascarenhas, director of the adult leukaemia programme at The Tisch Cancer Institute at Mount Sinai, New York, and one of the investigators in the study.

“The pelabresib and ruxolitinib combination therapy significantly reduced spleen volume – the best prognostic indicator we have at our disposal for long-term myelofibrosis patient outcomes,” he added.

MorphoSys has also highlighted a sub-population of intermediate-risk patients, in whom a 50% improvement in total symptom scores was seen in 55% of the combination arm and 45% of the Jakafi plus placebo group, just reaching statistical significance. That group accounted for nearly all (more than 90%) of the 430-strong study population.

The company is vying with rivals like AbbVie in the development of therapies that can be added to JAK inhibitors in first-line myelofibrosis therapies, notably AbbVie’s Bcl-2 inhibitor navitoclax, which is being tested in the TRANSFORM-1 study in combination with Jakafi in JAK inhibitor-naïve patients.

Initial results from that study discussed during AbbVie’s second-quarter results presentation earlier this year showed a significant improvement in the percentage of patients who achieved complete volume reduction of at least 35% compared to Jakafi plus placebo, at 63% versus 32% at 24 weeks.

That study also missed its secondary endpoints, but additional results are expected in the coming weeks, possibly at the American Society of Haematology (ASH) congress next month, and AbbVie has said it will decide on regulatory filings thereafter.

MorphoSys added pelabresib to its pipeline when it acquired US rival Constellation Pharma for $1.7 billion in 2021, a year before it slimmed down its clinical R&D pipeline to focus on its oncology candidates.

Earlier this year, analyst James Gordon of JP Morgan said peak sales for pelabresib could go as high as $1.7 billion annually, with a 50% probability of approval, despite an increasingly crowded market.