RARE Daily

Constellation Presents Positive Early Data in Myelofibrosis Study

November 7, 2019

Constellation Pharmaceuticals reported early data on CPI-0610, its experimental therapy for the treatment of myelofibrosis, which show encouraging clinical activity in an early stage trial of JAK-inhibitor naïve patients and transfusion-dependent ruxolitinib refractory or -intolerant patients.

Photo: Jigar Raythatha, president and CEO of Constellation Pharmaceuticals

Myelofibrosis is a rare disorder of the bone marrow where the marrow is replaced by fibrous tissue and causes anemia, which can lead to fatigue and weakness. I can also cause blood to pool in the liver and spleen. It typically develops after the age of 50 and in most cases gets progressively worse. Treatments include medications, blood transfusions, chemotherapy, and radiation therapy to alleviate symptoms.  

In its third quarter financial results, Constellation said preliminary data from the MANIFEST clinical trial of CPI-610 were published in abstracts for the upcoming meeting of the American Society of Hematology (ASH) where the data will be presented.

“The data in the abstracts show signs of encouraging clinical activity in both JAK-inhibitor-naïve patients and ruxolitinib-refractory or -intolerant patients. Based on this activity, we have expanded the MANIFEST trial in first-line patients and in second-line transfusion-dependent patients to look more closely at these signals of activity,” said Jigar Raythatha, president and CEO of Constellation.

In Arm 3, in which the company is evaluating CPI-0610 in combination with ruxolitinib in a first-line setting in JAK-inhibitor-naïve patients, all four evaluable patients experienced at least a 35 percent spleen volume reduction and at least a 50 percent reduction in total symptom score, which are the primary endpoints for these patients. This part of the study is being expanded to 100 patients from the 43 currently enrolled.

In Arms 1 and 2, in the company is evaluating CPI-0610 in combination with ruxolitinib and as a monotherapy in a second-line setting in ruxolitinib-resistant or -intolerant patients, additional preliminary data showed continuing signs of activity across a broad range of parameters, including spleen volume reduction, patient-reported symptom improvement, hemoglobin increases, conversion to transfusion independence in transfusion-dependent patients, and bone marrow fibrosis score improvement.

In Arms 1 and 2, conversions to transfusion independence increased from two as of April, to four as of June. Data from 12 additional patients are being monitored for possible additional conversions.

CPI-0610 was generally well-tolerated, both as a monotherapy and in combination with ruxolitinib. One ruxolitinib-resistant or -intolerant patient discontinued due to a erious adverse event that was reported as unlikely related to CPI-0610. No JAK-inhibitor-naïve patients discontinued due to adverse events.

Constellation says it is planning for a potential pivotal trial with CPI-0610 for myelofibrosis in the first-line setting that it expects to begin in 2020.

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