Jakafi One Step Closer to Approval for Polycythemia Vera

Jakafi Improves Symptoms in PV

In phase 3 randomized controlled trial, Jakafi (ruxolitinib) improved several key symptoms in polycythemia vera, according to Dr Srdan Verstovsek of MD Anderson Cancer Center in Houston.

Jakafi for Polycythemia VeraResults from the RESPONSE trial were presented at the 2014 ASCO (American Society of Clinical Oncology) annual meeting in Chicago.  PV is a myeloproliferative neoplasm that can be accompanied by debilitating symptoms and poor quality of life; leading to potential life-threatening cardiovascular complications related to thrombosis and hemorrhage.  Therapy is generally aimed at controlling hematocrit (HCT) below 45%, decreasing the risk of cardiovascular and thrombotic events.

Jakafi was significantly better than the best available therapy in PV patients who were resistant to or unable to tolerate hydroxyurea (HU).  In these patients the drug significantly improved control of hematocrit without the need for phlebotomy and reduced spleen size, two key goals of treatment.

The primary endpoint of the study was a composite HCT control (≤ 45%) and a reduction in spleen volume of at least 35%. At week 32, patients in the control arm were permitted to cross over to the jakafi arm and all but a handful did so, Verstovsek said.

At that point, he reported:

  • 21% of the jakafi patients had reached the composite endpoint, compared with 1% of those on best available treatment.
  • 60% of jakafi patients reached the hematocrit endpoint, compared with 20% on best available treatment.
  • 38% reached the spleen reduction goal, compared with 1% of those in the control arm.

Importantly, 91% of patients who reached the composite endpoint maintained the response at week 48, Verstovsek said. Also, 23.6% of jakafi patients reached a complete hematologic response, compared with 8.9% of control patients, a significant difference.

The drug also improved the total symptom score, as well as individual symptom clusters, he said, and with a median follow-up of 81 weeks, 85% of patients originally randomized to the drug were still taking it.

The main strength of the study was that it met a “well-conceived endpoint,” commented Guido Marcucci, MD, of Ohio State University Comprehensive Cancer Center in Columbus, in a formal discussion after the presentation.

It also met all of its secondary endpoints and showed that the drug had a “relatively favorable” safety profile, he said.

The main weakness, on the other hand, is that almost all of the control patients crossed over to the jakafi arm as soon as they were able, Marcucci said.

“We don’t have data yet on those patients,” he said, and it would be interesting to know if they have the same favorable response.

He also noted that there is no pharmacodynamic data, which is “important because we want to know why only 21% and no more had a response.”

Marcucci added that the study shows the drug improves the symptoms of the disease, but it remains an open question whether it changes the natural history of the disease.

The study was supported by Novartis. Verstovsek disclosed relationships with Incyte. Employees of both companies were among the authors.

Marcucci had no disclosures.

More details on the study can be found here and on this article.


Publisher’s Note

The study used Hydroxyurea (HU) as best available therapy for the control arm.  While HU has been the standard for many years, many MPN specialists favor peginterferon alfa-2a (Pegasys) for it’s ability to achieve “minimal residual disease”, reduce the allele burden, possibly prevent progression while controling symptoms.  Dr Hans Hasselbalch prefers combo therapy which includes IFN, a JAK2 inhibitor and a statin drug.  It would be interesting to see how Jakafi fares against Pegasys in a similar study.


About David Wallace

Founder of PV Reporter, a resource for Myeloproliferative Neoplasm (MPN) patients and caregivers. After being diagnosed with Polycythemia Vera (PV) in 2009, I utilized social media to connect with "informed patients" and develop a better understanding of emerging treatment options. My philosophy on patient care is straight forward - "educating the patient is essential, so the patient can guide their physician to meet his or her needs." PV Reporter is a comprehensive resource hub giving visitors vital tools to become "empowered patients."

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