Shares of Incyte Corp. (NASDAQ:INCY) lit up Wednesday morning after the company reported top-line results of ruxolitinib (Jakafi), which showed noticeable survival benefit in a Phase II study in refractory metastatic pancreatic cancer. The stock opened higher, climbing more than 38 percent to top $37 a threshold not breached by the company since 2000 before closing at $36.04 for a gain of $9.04 on the day. More than 18 million shares changed hands 15 times the daily average.
The randomized, double-blind, placebo-controlled RECAP trial of the oral Janus kinases 1 and 2 (JAK1 and JAK2) inhibitor, in combination with capecitabine, showed that six-month survival was 42 percent in the ruxolitinib arm for a pre-specified subgroup representing 50 percent of the randomized population, compared to 11 percent for placebo. The subgroup was identified prospectively as most likely to benefit from JAK pathway inhibition.
The hazard ratio (HR) for overall survival (OS) was 0.79 (one-sided p = 0.12) in the intent-to-treat population and 0.47 (one-sided p = 0.005) in the pre-specified subgroup analysis. Durable tumor responses were observed only in patients receiving ruxolitinib, and patients treated with ruxolitinib achieved significant improvement in body weight compared to placebo, according to the company.
"We were somewhat surprised at the magnitude of the benefit in this subgroup," admitted Richard Levy, Incyte's executive vice president and chief drug development and medical officer, acknowledging the company was aware of the challenges in pancreatic cancer. "We're happy to see that this undisclosed way that we can direct patients into future studies really does result in a very impressive difference in survival."
Ruxolitinib, in combination with capecitabine, was generally well tolerated, with 12 percent of patients in the treatment arm discontinuing therapy for an adverse event compared to 20 percent who received capecitabine alone. The rates of new onset Grade 3 anemia, thrombocytopenia and neutropenia were 16 percent, 2 percent and 0 percent, respectively, in the treatment arm compared to 2 percent, 3 percent and 2 percent, respectively, in the capecitabine-only arm.
The study consisted of an open-label, safety run-in period with nine patients, followed by a double-blind study of 127 patients randomized 1:1 to capecitabine plus ruxolitinib or capecitabine plus placebo. In addition to the primary OS endpoint, secondary endpoints included progression-free survival, body weight and nutritional markers, tumor response rate, quality-of-life outcomes and pain status.
Wilmington, Del.-based Incyte plans to move as quickly as possible into a Phase III study in metastatic pancreatic cancer.
"Obviously, we want to work with the FDA, and this data is brand new so they haven't seen it," Levy told BioWorld Today. "Our hope is that we would be moving into Phase III in the first half of next year, and the sooner, the better. But it's hard to get granular before you've had those discussions with regulators."
'Real Opportunity' in Other Solid Tumors
In 2011, Jakafi became the first JAK inhibitor approved by the FDA and the first drug to treat the initial indication of bone marrow disease myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF. (See BioWorld Today, Nov. 17, 2011.)
Earlier this month, Incyte reported $54. 1 million in second-quarter U.S. sales of Jakafi and projected full-year net revenues from Jakafi in the range of $220 million to $230 million. Product royalties from sales outside the U.S., where the drug is branded Jakavi, by partner Novartis AG, of Basel, Switzerland, reached $5.8 million in the second quarter. That collaboration and licensing deal swelled Incyte's coffers with $150 million up front, plus $60 million as an "immediate development milestone," with potential payments of more than $1 billion over time. (See BioWorld Today, Nov. 30, 2009.)
Not surprisingly, Incyte now is looking to advance the ruxolitinib and JAK1 inhibitor programs into additional solid tumor populations, using its method to identify patients responsive to JAK inhibition without use of a companion diagnostic. Levy made clear that the subgroup identified for RECAP is not specific to pancreatic cancer and that the company's screening methodology relates to the basic mechanism of JAK inhibitors.
"We think that there is a real opportunity in a large number of potential solid tumors," he said, adding that Incyte has not yet finished its internal data analyses to determine the next indications beyond second-line pancreatic cancer.
The company plans to submit the RECAP data for presentation at a future scientific meeting. Due to the applicability of the findings to a wide range of solid tumors, Levy said the American Society of Clinical Oncology annual meeting in June 2014 would provide the most "appropriate" setting.
In light of the pancreatic cancer findings, Levy said the company's board of directors will examine Incyte's portfolio as part of their annual strategy review to determine whether to reposition any candidates. So far, "no decisions have been made to step away" from any compounds in the pipeline, he added.
Rave reviews by analysts likely drove some activity in the company's stock. Brean Capital LLC analyst Jonathan Aschoff bumped his price target to $38 from $27, citing the "impressive" pancreatic cancer data and projecting product approval in 2016.
Wells Fargo Securities LLC analyst Brian Abrahams also increased his valuation range to $35 to $37, from $25 to $27, writing in a company note that "based on what we know so far from these results, we feel more confident Jakafi could have a meaningfully larger long-term opportunity than if it were only used in specific heme/onc cancers." He projected Incyte's revenue from Jakafi could reach $950 million by 2017.
RBC Capital Markets analyst Michael Yee put a slightly different spin on the data, writing in a research update that "interestingly, we see a slightly positive read-through to other JAK1 players who could theoretically investigate a similar patient population." As prospects, he suggested Gilead Sciences Inc., of Foster City, Calif., which inherited JAK1/2 inhibitor CYT387 through its 2012 acquisition of Canadian biotech YM Biosciences Inc.; the Galapagos NV/Abbvie partnership in GLPG0634, a selective JAK1, in rheumatoid arthritis (RA); and Pfizer Inc., which has the JAK inhibitor Xeljanz (tofacitinib citrate) in RA. (See BioWorld Today, March 1, 2012, Nov. 8, 2012, and Dec. 13, 2012.)
Incyte is investigating a separate JAK1/2 inhibitor, baricitinib, in RA, Yee pointed out. That program, partnered with Eli Lilly and Co. Inc., is in Phase III studies, with initial data expected to report in the second half of next year. (See BioWorld Today, Nov. 15, 2012.)