FDA approves first drug to treat patients with a chronic type of bone marrow disease

Dr Opdycke

FDA approved a new use for ruxolitinib (Jakafi, Incyte) to treat patients with polycythemia vera (PV), a chronic type of bone marrow disease. Jakafi is the first drug approved by FDA for this condition.

PV occurs when too many red blood cells are made in the bone marrow. Patients may also experience an increase in white blood cells and platelets. An overabundance of blood cells can cause the spleen to swell, bleeding problems and blood clots in the veins near the skin surface (phlebitis). In addition, it puts patients at increased risk of stroke or heart attack.

Approximately 100,000 patients in the United States have PV.

Jakafi’s new use is intended to treat PV patients who have an inadequate response to or cannot tolerate hydroxyurea, another drug often prescribed to reduce the number of red blood cells and platelets in the blood. Jakafi works by inhibiting enzymes called Janus Associated Kinase (JAK) 1 and 2 that are involved in regulating blood and immunological functioning. The drug’s approval to treat PV will help decrease the occurrence of an enlarged spleen (splenomegaly) and the need for phlebotomy, a procedure to remove excess blood from the body. 

FDA drug approvals-December 2014

“FDA’s approval . . . will generate interesting discussions at P&T committee meetings,” according to Ruth Opdycke, PharmD, MS, president of TPG Healthcare Consulting LLC, in Glastonbury, Conn.

“For this rare condition, we now have the first FDA approved JAK1/JAK2 alternative for hydroxyurea non-responders that will cost more than $100,000 per year per patient compared to under $500 per year per patient for hydroxyurea,” said Dr Opdycke. “Both products are taken orally.”

Prior to Jakafi, the injectable interferon alpha products were considered second-line, off-label alternative to hydroxyurea, according Dr Opdycke. “The interferon alpha products cost less than half that of Jakafi. From a pure-play labeled-indication perspective, hydroxyurea for PV is considered ‘off label’ use for PV. Will P&T committees consider a stepped-therapy approach for hydroxyurea non-responders and require use of another off-label product-interferon alpha-prior to Jakafi?”

“Further complicating this issue, are the results of the RELIEF trial which did not demonstrate a statistically significant difference between Jakafi and hydroxyurea in achieving the primary end point of symptom control in PV patients who were generally well-controlled on hydroxyurea but still reporting disease-related symptoms,” according to Dr Opdycke.

RELIEF was a randomized, double-blind clinical trial designed to compare symptom improvement in 110 patients with PV treated with ruxolitinib versus patients treated with hydroxyurea, were released.

According to Incyte, while positive trends were observed in favor of ruxolitinib, RELIEF did not achieve statistical significance for the primary end point as measured by the proportion of patients with ≥50% reduction in a defined cluster of symptoms that included tiredness, itching, muscle aches, night sweats and sweats while awake at week 16 compared to baseline. Topline results showed a 43.4% symptom response rate in the ruxolitinib arm and a 29.6% symptom response rate in the hydroxyurea arm (P=.139).

“P&T committees will need to consider the options for utilization management controls to minimize the potential for Jakafi to be used ‘off label’ as a first line agent in place of hydroxyurea,” she said.

Jakafi’s approval for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea was based on data from the pivotal phase 3 RESPONSE trial, which was conducted under a Special Protocol Assessment from FDA. Patients treated with Jakafi demonstrated superior hematocrit control and reductions in spleen volume compared to best available therapy. In addition, a greater proportion of patients on the ruxolitinib treatment arm achieved complete hematologic remission-which was defined as achieving hematocrit control, and lowering platelet and white blood cell counts. In the RESPONSE trial, the most common hematologic adverse reactions (incidence > 20%) were thrombocytopenia and anemia. The most common non-hematologic adverse events (incidence >10%) were headache, abdominal pain, diarrhea, dizziness, fatigue, pruritus, dyspnea and muscle spasms.

The study was designed to measure the reduced need for phlebotomy beginning at Week 8 and continuing through Week 32, in addition to at least 35% reduction in spleen volume at Week 32. Results showed 21% of Jakafi-treated participants experienced a reduction in the need for a phlebotomy and a reduction in spleen volume, compared to 1% of participants who received best available therapy.

Low red blood cell counts (anemia) and low blood platelet counts (thrombocytopenia) were the most common side effects associated with use of Jakafi in participants with PV. The most common non-blood related side effects were dizziness, constipation and shingles.

FDA reviewed Jakafi’s use for PV under the agency’s priority review program. Jakafi also received orphan product designation.

Jakafi was approved in 2011 for treatment of patients with another bone marrow disorder, intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.