Constellation Pharmaceuticals announced on Sunday that it has received preliminary data from its Phase II MANIFEST and Phase III MANIFEST-2 clinical trials involving CPI-0610 for myelofibrosis.
Photo courtesy of Constellation Pharmaceuticals.
Constellation Pharmaceuticals announced on Sunday that it has received preliminary data from its Phase II MANIFEST and Phase III MANIFEST-2 clinical trials involving CPI-0610 for myelofibrosis (MF). The information was presented at the American Society of Hematology (ASH) Annual Meeting and Exposition.
In the Phase II MANIFEST trial, Constellation looked at how CPI-0610 could work in combination with ruxolitinib in JAK-inhibitor-naïve MF patients. The primary endpoint was the proportion of patients with a ≥35% spleen volume reduction from baseline (SVR35) after 24 weeks.
The Phase III MANIFEST-2 trial examined how CPI-0610 in combination with ruxolitinib (versus placebo with ruxolitinib) could impact JAK-inhibitor-naïve patients with primary myelofibrosis or post-ET or post-PV myelofibrosis who have splenomegaly and symptoms requiring therapy. The primary endpoint was a ≥35% reduction in spleen volume (SVR35) from baseline at 24 weeks.
In Arm 1, which looked at CPI-0610 as a monotherapy in JAK-inhibitor-experienced or ineligible patients, 30% of evaluable patients who were not transfusion dependent (TD) at baseline achieved SVR35 at 24 weeks. In Arm 2, which examined CPI-0610 in combination with ruxolitinib in ruxolitinib-experienced patients, 29% of evaluable non-TD subjects achieved SVR35 at 24 weeks.
Finally, in Arm 3, which looked at CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve patients, 67% of subjects achieved a ≥35% reduction in SVR35 at the 24-week mark.
“We are pleased both with the response rates and consistency of the results we are seeing in MANIFEST,” said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. “In addition, we are excited by results from our translational studies that suggest that CPI-0610 may potentially be a disease modifying therapy that affects all four hallmarks of myelofibrosis. We are pleased to have initiated MANIFEST-2, our global registrational study of CPI-0610, in JAK-inhibitor-naïve MF patients.”
Overall, CPI-0610 was well-tolerated in MANIFEST. This accounts for when it was used as a monotherapy and in combination with ruxolitinib.
Constellation initially reported results from the MANIFEST clinical trial using posters with the latest data back in June of this year. At the time, the information was published online in association with the European Hematology Association’s annual meeting.
The data showed that at the 12-week mark in Arm 1, about 58% of non-TD patients on treatment without any necessary transfusions achieved a ≥1.5 g/dL mean increase in hemoglobin. At the 24-week mark in Arm 2, approximately 37% of evaluable non-TD patients had achieved an improvement in Total Symptom Score (TSS50). Finally, 63% of patients in Arm 3 achieved SVR35 at the 24-week mark.
“I’m encouraged that the initial signals of activity with CPI-0610, such as spleen and symptom responses, that were presented last December at ASH continue to be observed in a larger dataset presented in these EHA posters,” said Claire Harrison, D.M. (Oxon.), Professor of Haematology and a MANIFEST investigator, at the time of the announcement. “In addition, we continue to see signals of disease modification, such as increases in hemoglobin, conversions of transfusion-dependent patients to transfusion independence, and bone marrow fibrosis improvements. If corroborated in further testing, these data suggest that CPI-0610 could potentially change the treatment paradigm in MF.”
At this point in the studies, CPI-0610 was also well tolerated as a monotherapy and in combination with ruxolitinib and in both JAK-inhibitor-naïve and JAK-inhibitor-experienced and ineligible patients.
As for the most recent translational data, 33% of patients with evaluable samples across all three treatment arms had one grade or greater improvement in bone marrow fibrosis. In addition, improvements occurred within six months of treatment for 84% of these patients, suggesting promise in CPI-0610.
Featured Jobs on BioSpace
