Promising Myelofibrosis Therapies Are in the Pipeline

Danielle Bucco

While the use of Jakafi (ruxolitinib) is firmly rooted in the treatment paradigm for patients with myelofibrosis, other novel agents, such as momelotinib and pacritinib are also gaining the interest of researchers in the field.

The phase 3 SIMPLIFY-2 trial missed its primary endpoint of superiority with momelotinib in patients with myelofibrosis who had a reduction in spleen volume at 24 weeks. The study was comparing momelotinib versus best alternative therapy at 6.7 percent versus 5.8 percent, respectively.

However, momelotinib met its secondary endpoint of response rate in total symptom score (TSS), as well as an endpoint related to anemia.

In the phase 3 SIMPLIFY-1 trial, momelotinib did achieve the primary endpoint of noninferiority versus Jakafi when measuring the percentage of patients with myelofibrosis who had at least a 35 percent reduction in spleen volume at 24 weeks at 26.5 percent versus 29 percent, respectively. Noninferiority for momelotinib was not demonstrated for the important secondary endpoint of response rate in TSS at week 24.

“Momelotinib did not show superiority, but there was an improvement in anemia compared with ruxolitinib,” said Alice Mims, M.D.. “In my opinion, there is a role for momelotinib in the future for these patients.”

In an interview with CURE, Mims, a medical oncologist at The Ohio State University Comprehensive Cancer Center, provided updates on the field of myeloproliferative neoplasms, with a focus on myelofibrosis.

Please provide an overview of your recent presentation on myelofibrosis treatment at the 2017 OncLive State of the Science Summit on Hematologic Malignancies.

We discussed myelofibrosis and how there are very limited treatments other than symptomatic therapies. The most exciting therapy has been Jakafi, which is a JAK 1/2 inhibitor that has been shown to improve symptomatic splenomegaly as well as constitutional symptoms. However, Jakafi can have side effects that cause progressive anemia and it cannot be given in patients with thrombocytopenia.

We are excited because there are newer JAK inhibitors that are being investigated in clinical trials that have also reduced spleen size, as well as improve anemia. These are agents such as momelotinib and pacritinib. 

What are the biggest challenges that remain with Jakafi?

One of the biggest questions is the overall survival (OS) that we discussed at this meeting.  There has been a report of the five-year follow-up that discusses what the OS benefit might be with Jakafi versus the best available therapy or placebo. The clinical trial design with the allowance of crossover has a lot of confounding data, making it difficult to say if that is a true entity or not. That is one of the big questions about survival data. 

What data have we seen with momelotinib and pacritinib?

For momelotinib, there were the SIMPLIFY studies. The SIMPLIFY-1 study looked to see if Jakafi was noninferior in patients, and it did demonstrate that it was noninferior in the reduction of splenic size.

The SIMPLIFY-2 study investigated the superiority of momelotinib compared with Jakafi. Momelotinib did not show superiority; however, there was an improvement in anemia compared with Jakafi. In my opinion, there is a role for momelotinib in the future for these patients.

Regarding pacritinib, there are still some unanswered questions. Pacritinib was put on hold by the FDA due to concerns for cardiac toxicity and mortality, but this was recently lifted in patients with myelofibrosis. It is being reassessed at different dosing levels. It also has improvement of anemia, so there may be a role for pacritinib based on the outcomes of that data. 

What are the big remaining challenges for patients with myelofibrosis?

One challenge is there is not curative therapy other than allogenic transplant. However, the majority of patients are not going to be candidates. Also, therapy has been shown to reverse fibrosis itself, which creates the question of whether there are any therapies that might be able to do that for patients.

Are there any known risk factors for developing myelofibrosis?

The only known risk factor for myelofibrosis is if a patient has another myeloid malignancy, specifically a myeloproliferative disorder, such as polycythemia vera or central thrombocytopenia. About 10 percent to 20 percent of patients with myelofibrosis will have those proceeding their diagnosis. 
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