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Ruxolitinib Approved for Myelofibrosis in European Union


ugust 29, 2012 — The European Union has approved ruxolitinib, the first drug for the treatment of myelofibrosis.
Ruxolitinib, an oral inhibitor of JAK1 and JAK2, was approved for disease-related splenomegaly or symptoms in adults with primary myelofibrosis (chronic idiopathic myelofibrosis), postpolycythemia vera myelofibrosis, or postessential thrombocythemia myelofibrosis.
Ruxolitinib will be marketed in the European Union as Jakavi by Novartis, which has licensed the drug from Incyte, which already markets it as Jakafi in the United States. When it was approved in the United States in November 2011, it was the first ever drug for myelofibrosis.
The approvals are based on a pair of pivotal phase 3 studies, known as COMFORT (Controlled Myelofibrosis Study With Oral JAK Inhibitor Therapy)-1 and -2.
Myelofibrosis is characterised by bone marrow failure, an enlargement of the spleen, debilitating symptoms (such as extreme fatigue, night sweats, and intractable pruritus), poor quality of life, and weight loss. It also shortens survival.
Both COMFORT studies showed that treatment with ruxolitinib reduced splenomegaly and other symptoms. COMFORT-1 found that 41% of patients treated with ruxolitinib achieved at least a 35% reduction in spleen volume at 24 weeks, compared with 0.7% of patients treated with placebo (P < .001). COMFORT-2 found a similar reduction in spleen size at 48 weeks in 28% of patients treated with ruxolitinib, compared with 0% of patients treated with best available therapy (P < .001).
There was also improvement in other symptoms after treatment with ruxolitinib, including functioning, fatigue, pain, and loss of appetite.
The approval in the European Union "brings an urgently needed new treatment option with the potential to make a real difference to patients' lives," stated principal investigator on COMFORT-2, Claire Harrison, MD, from Guy's and St. Thomas' NHS Foundation Trust in London, United Kingdom. Ruxolitinib "delivers a rapid and durable benefit that has the potential to become a new standard of care," she said in a statement released by Novartis.
Novartis noted that the most common adverse drug reactions (incidence >10%) are urinary tract infections, anemia, thrombocytopenia, neutropenia, hypercholesterolemia, dizziness, headache, liver enzyme elevations, bruising, bleeding, and increased blood pressure. Complete blood monitoring is recommended.
Studies Published
Both COMFORT studies were published earlier this year (N Engl J Med. 2012;366:787-798, 799-807).
In an interview with Medscape Medical News at the time, Dr. Harrison explained that ruxolitinib had "an unprecedented benefit in terms of quality-of-life concerns for patients." COMFORT-1 showed this against placebo, and COMFORT-2 showed this even more convincingly against the physician's choice of best available therapy, she said. "The spectrum of drugs that are currently available to treat these patients does not have anything like the quality-of-life responses that we saw with ruxolitinib."
However, the author of an editorial accompanying the publication of the COMFORT studies was a little less enthusiastic about the benefits (N Engl J Med. 2012;366:844-846). Ayalew Tefferi, MD, from the division of hematology at the Mayo Clinic in Rochester, Minnesota, explained that ruxolitinib does not affect the underlying disease and offers only transient palliation of some symptoms. He also noted that it does not improve survival, has adverse effects, including myelosuppression, and is expensive.
Dr. Tefferi suggested that ruxolitinib is only suitable for some patients with myelofibrosis, possibly only 25%; even then, it might not be the best option.
However, he told Medscape Medical News in an interview at the time that "I don't believe that anyone doubts...that it is a useful addition to the treatment options [for myelofibrosis]."
"We don't just treat patients to prolong their lives, we also treat them to make them feel better," he said.

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