Incyte Corp. is in the rare position of being able to claim quality of life benefits for its newly approved drug Jakafi (ruxolitinib) for myelofibrosis, a progressive cancer of the bone marrow that forces blood cell creation into other organs, causing enlargement of the spleen and anemia.

While spleen shrinkage was the primary endpoint in pivotal trials, Incyte also measured the effect of the drug on the symptoms of the disease, using a patient-reported outcomes tool that became a secondary endpoint of its pivotal Phase III COMFORT I trial.

Jakafi was approved Nov. 16 to treat patients with intermediate or high-risk myelofibrosis based on the primary endpoint, but in addition to data on that outcome, the clinical studies section of labeling includes data on that secondary endpoint: the modified Myelofibrosis Symptom Assessment Form 2.0 diary, a PRO metric developed by Incyte following FDA guidance and advice.

FDA invested 12 years in shaping a guidance on patient-reported outcomes measures, and published the final document in December 2009 Also see "FDA's Final PRO Guidance Grounds Policy With More Details" - Pink Sheet, 8 December, 2009..

“We are the first drug for an oncology indication that has used the patient-reported outcome guidance, at least successfully,” Richard Levy, Incyte’s chief of drug development and chief medical officer, said in an interview. “It’s really been probably more than 10 years since any oncology drug had any endpoint based on anything related to symptoms or quality of life.”

The MFSAF and the data generated were submitted as a secondary endpoint for COMFORT I under a special protocol assessment with the agency. Being able to address the way patients feel is something patient advocates have been lobbying for, particularly in the cancer arena, for a long time, Levy said, but he sought to disabuse the notion that FDA has been slow to accept PRO measures in support of efficacy claims.

Levy said he thinks it’s been tough to actually find the right drug to clearly demonstrate improvement in symptoms as well as a disease that was so clear cut, adding his opinion that “part of the problem as far as the FDA has been concerned, is that companies have not been coming to them, particularly in cancer, asking for endpoints based on symptoms.”

“We as a company took [MFSAF] to the FDA and fostered that,” Levy said.

The symptoms monitored via the MFSAF were night sweats, itching, bone and muscle pain, abdominal discomfort, pain under the left ribs (where the spleen is) and early satiety, the sensation of being full and not wanting to eat. According to labeling, the proportion of patients with at least a 50% reduction in a total daily score compiled from individual daily ratings was 45.9% for patients on Jakafi and 5.3% for patients taking a placebo (p<>

The MFSAF was used in the randomized, blinded COMFORT I trial, conducted in the U.S., Canada and Australia by Incyte, but not in the unblinded COMFORT II, conducted in Europe by co-developer Novartis AG. In retrospect, with the robust results of the blinded trial in hand, MFSAF might have been a useful addition to the European trial, but “we’re happy with the way things turned out nonetheless,” Levy said during a presentation Nov. 10 at the Conference on Clinical Cancer Research in Washington, D.C., sponsored by the Engelberg Center for Health Care Reform at Brookings and Friends of Cancer Research.

One Of Several Firsts For Incyte

In addition to being the first company to successfully use a PRO tool to gain approval of an oncologic, with the Jakafi approval Incyte has the first approval of a Janus-Associated Kinase (JAK) inhibitor, in this case an inhibitor of JAK1 and JAK2. JAKs mediate signaling of cytokines that cause inflammation, and in addition to the cancer itself, disregulation of that pathway is thought to be the root of the symptoms ameliorated by Jakafi, Levy said. The class is being investigated in a number of therapeutic areas Also see "JAK Of All Trades: Janus Kinase Inhibitors Are Ready, Willing And Orally Available For Many Diseases" - Pink Sheet, 1 February, 2011..

Jakafi is also the first treatment to be FDA-approved for myelofibrosis, a rare form of cancer that affects only about 15,000 to 20,000 patients in the U.S., about 80%-90% of whom are covered by the labeled indication. The approval covers a broader range of patients than was included in clinical trials for the drug, allowing treatment of those whose disease is classified as intermediate-1 through high-risk. Only low-risk patients, who comprise about 15% of the patient population, are not eligible for use of the drug per labeling.

In addition, the NDA was granted a six-month priority review that was shortened even further by an early approval; the PDUFA data was Dec. 3. The approval came with no requirement for new post-marketing trials and no risk management requirement. “The reason we got a full approval is a demonstration of true benefit,” Levy said.

Jakafi is priced at a flat $7,000 per month for all five dosage strengths.

Incyte Corp.

Jakafi will also be Incyte’s first product launch. The drug will be available the week of Nov. 21 in five strengths with a flat wholesale acquisition cost of $7,000 for a 30-day supply. Flat pricing appeals to payers and ensures that patients get the strength they need, Patricia Andrews, chief commercial officer, said during an investors call Also see "Incyte’s Jakafi Gets Broad Label, Early Approval For Myelofibrosis" - Pink Sheet, 16 November, 2011..

Dosing of Jakafi is based largely on platelet count, with adjustments recommended for patients who are taking strong CYP3A4 inhibitors or who have renal or hepatic impairment, and the drug will be available in 5 mg, 10 mg, 15 mg, 20 mg and 25 mg tablets to accommodate those adjustments.

All that remains for Incyte – and it will be no small task – is to execute a successful launch Also see "Sell The Launch: Going Commercial, Some Biotechs Are Left Hanging" - Pink Sheet, 5 September, 2011.. Incyte has contracted with five specialty pharmas, hired and trained 60 experienced field-based “territory business managers” to call on approximately 6,500 treating physicians, primarily specialists in hematology and oncology, and instituted a patient assistance program called IncyteCares.

Still, considering the small patient pool and the time it may take to educate physicians, the company is anticipating a slow uptake curve and declined to make sales projections until after the commercial picture clarifies. Nonetheless, Incyte banked a $10 million milestone payment from Novartis on the approval, pushing its fourth quarter revenue guidance to $92 million Also see "Novartis/Incyte Move Forward With JAK Inhibitor For MF" - Pink Sheet, 15 March, 2011..

Incyte’s Jakafi Gets Additional Claim Based On Patient-Reported Outcomes

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