MorphoSys has reported positive topline results from the Phase III MANIFEST-2 clinical trial investigating pelabresib in myelofibrosis. 

The trial evaluated pelabresib in combination with Novartis and Incyte’s Jakafi (ruxolitinib). compared to placebo plus Jakafi in JAK inhibitor-naïve patients with myelofibrosis.  

The trial met its primary endpoint and demonstrated a statistically significant and clinically meaningful improvement in the proportion of patients achieving at least a 35% reduction in spleen volume at week 24.  

Key secondary endpoints related to symptom improvement such as a 50% reduction in total symptom score (TSS50) and absolute change in total symptom score (TSS). The results demonstrated a positive trend favouring the combination of pelabresib and Jakafi. 

The global, double-blind, multicentre trial (NCT04603495) enrolled 430 patients across 23 countries.   

Pelabresib is an investigational bromodomain and extra-terminal (BET) inhibitor designed to promote anti-tumour activity. The candidate has not yet been approved by any regulatory authorities, but MorphoSys intends to submit for approval in the US and Europe in mid-2024.  

In the announcement accompanying the results, the Tisch Cancer Institute in New York adult leukaemia programme director John Mascarenhas said: “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.

"Based on insights from MANIFEST-2, pelabresib represents a promising and well-tolerated therapeutic option for a community in need of innovation.” 

The US Food and Drug Administration (FDA) has approved four innovator treatments for myelofibrosis, all of which are Janus kinase (JAK) inhibitors. One of them is Jakafi, which was approved in 2011. The drug has generated $1.2bn in global sales in H1 2023, as per Incyte’s Q2 financial report. 

However, concerns have been raised over these drugs, as this mechanism of action is well known for myelosuppression, which can induce and worsen symptoms of anaemia and reduce oxygen circulation throughout the body. The FDA has been steering away from this drug class, as only two of the 12 drugs that received orphan drug designation (ODD) by the FDA since 2014 act via JAK inhibition. 

Myelofibrosis is a rare chronic bone marrow disorder characterised by the abnormal production of blood cells, leading to fibrosis in the bone marrow, enlarged spleen, and a range of associated symptoms. According to a report by GlobalData, the myelofibrosis market will grow to $2.89bn in 2031. 

GlobalData is the parent company of Clinical Trials Arena.