https://www.onclive.com/view/pelabresib-ruxolitinib-data-undersco...

https://www.onclive.com/view/pelabresib-ruxolitinib-data-underscore-need-for-novel-end-points-in-myelofibrosis-trials
https://firstwordpharma.com/story/5876742

A few exec's over at Novartis sweating their $2.9 acquisition.

MANIFEST-2 hit the primary endpoint of spleen volume response but missed the secondary endpoint of total symptom score response.

MANIFEST-2 presented at the 2024 ASCO Annual Meeting showed that patients with myelofibrosis who received frontline pelabresib (CPI-0610) plus ruxolitinib (Jakafi; n = 214) experienced an SVR35 rate of 65.9% at week 24 compared with 35.2% for those given ruxolitinib plus placebo (n = 216). Notably, updated data showed that in patients who experienced an SVR35 at any time, 13.4% of patients in the experimental arm lost that response vs 27.8% of patients in the placebo arm.

Additionally, the TSS50 rates at week 24 were 52.3% for pelabresib plus ruxolitinib vs 46.3% for placebo plus ruxolitinib, translating to a numerical improvement that was not statistically significant (difference, 6.0%; 95% CI, –3.5% to 15.5%; nominal P = .216).

Notably, 40.2% of patients in the pelabresib arm experienced both SVR35 and TSS50 at week 24 compared with 18.5% of patients in the placebo arm.

Query over safety.

There was a concern over an increased risk of leukemic transformation and increased proportion of patients with blast transformation. If we look at pelabresib plus ruxolitinib, 2.4% of patients [in the combination arm] vs 0.5% of patients on placebo plus ruxolitinib [experienced blast phase progression].


I like this from Mr Gerds

"We have drugs that are good at making patients’ symptoms better; however, we need are drugs that truly modify the disease course in a meaningful way,” Gerds explained."