In addition to awaiting an FDA decision on its new once-daily formulation of Jakafi® (ruxolitinib), Incyte is counting on a series of Phase II and III data readouts to set the stage for finally broadening the company’s revenue base beyond the billions in sales generated by its longtime blockbuster.
The FDA has set a March 23 target date under the Prescription Drug User Fee Act (PDUFA) to decide on Incyte’s new drug application (NDA) for a once-daily extended-release version of ruxolitinib with the same indications as Jakafi: myelofibrosis, polycythemia vera, and graft vs. host disease (GVHD).
However, Incyte CEO Hervé Hoppenot told GEN Edge that the company is especially eager to see data from studies assessing ruxolitinib in several combinations with other drugs in its pipeline—starting with the Phase III LIMBER-304 trial (NCT04551053) of ruxolitinib with parsaclisib, a next-generation oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), in myelofibrosis patients who are suboptimal responders to ruxolitinib alone. Data from LIMBER-304 is expected in the second half of this year.
The combination is also under study as a first-line therapy in a Phase III LIMBER-313 trial (NCT04551066).
Last December, at the 64th American Society of Hematology (ASH) annual meeting in New Orleans, Incyte presented final data (Abstract #236) from a Phase II trial (NCT02718300) in suboptimal myelofibrosis patients. The data showed that three dosages of the ruxolitinib-parsaclisib combination met the study’s primary endpoint of change in spleen volume from baseline to week 12, with 59.5% (25), 21.4% (9), and 4.8% (2) of patients dosed daily experiencing ≥10%, ≥25%, and ≥35% reduction in spleen volume, respectively.
“The standard of care today for these patients is to continue Jakafi, because if you stop, in fact, the symptoms would be way worse, and the spleen will start growing very, very quickly,” Hoppenot said. “People today are not fully satisfied, but they are good enough to continue on Jakafi. That’s exactly what we’re trying to improve.”
Later this year, Incyte also expects to release Phase II data in myelofibrosis patients from separate combination trials of ruxolitinib with two other drugs in the company’s pipeline: with the selective accumulated knowledge of activin receptor-like kinase 2 (ALK2) inhibitor INCB00928 (zilurgisertib); and with the bromodomain and extra-terminal (BET) inhibitor INCB57643.
At ASH, Incyte presented data from a Phase I/II open-label, dose escalation, and expansion study (INCB 00928-104, NCT04455841) showing a reduction in post-dose hepcidin levels at all dose levels and improvements in anemia among patients treated in both the monotherapy and combination cohorts, which according to the company suggest the potential for therapeutic activity. The data also supported once-daily dosing of INCB00928 and continued dose escalation to achieve optimal exposure.
Jakafi sales have remained robust in 2022. At the J.P. Morgan 41st Healthcare Conference earlier this month, Incyte projected Jakafi sales for 2022 of $2.38-2.4 billion, up between 11.5% and 12.4% from the $2.135 billion racked up in 2021 (itself a 10% jump from 2020 sales).
The company will release formal fourth-quarter and full-year 2022 results on February 7.
Incyte has issued no formal investor guidance on its second marketed drug Opzelura™, a topical cream version of ruxolitinib that won FDA approval in July 2022 for a second indication, nonsegmental vitiligo in adults and pediatric patients 12 years and older. However, the company has disclosed that Opzelura has generated $67.45 million in the first three quarters of 2022. (2021 revenue for Obzelura was “not meaningful,” according to Incyte.)
Of Obzelura’s revenue total, $38.14 million came in Q3. That number was 27% above a consensus estimate cited by Andrew Berens, MD, senior managing director, targeted oncology and a senior research analyst with SVB Securities, who credited the company for curtailing free access to the drug for patients following its launch to market in vitiligo.
“Going forward, we believe a key question will be whether this process of converting free drug into paid prescriptions adversely impacts demand as patients may bear higher out-of-pocket expenses, and the process may involve more steps in accessing the drug,” Berens pondered in a November 2022 research note.
The vast majority of Opzelura’s revenue came from patents treated for the drug’s first indication of short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.
The FDA granted that first indication in 2021, enabling dermatologists to prescribe Opzelura upon referral from general practitioners treating the disease with steroids, and as an alternative to systemic therapies like Sanofi and Regeneron Pharmaceuticals’ Dupixent® (dupilumab).
“What’s good news now is that we are at the stage where we have good insurance coverage. Most of the plans are including Obzelura,” Hoppenot said. “The fact that there is no other approved product in AD is obviously very helpful there.”
According to a 2020 journal review article cited by Incyte, 1.5 million people in the United States are diagnosed annually with vitiligo, with no FDA-approved product for repigmentation available until Obzelura came to market. “If only a fraction of the 1.5 million people are coming to their dermatologist asking for Obzelura, it would be a big opportunity for them, and for us,” Hoppenot said.
In vitiligo, he said, patients have begun driving sales by sharing their stories, complete with before-and-after photos, on social media. European regulators will decide on adding a vitiligo indication for Opzelura following an opinion from the Committee for Medicinal Products for Human Use (CHMP) expected in the first half of 2023.
Incyte is also developing Opzelura for pediatric AD, where data from a Phase III trial (NCT04921969) is set to come out in the second half of this year; and for lichen planus and lichen sclerosus, for which Incyte is studying the drug in Phase II trials (NCT05593432 and NCT05593445, respectively).
“It’s an indication where we believe that the Jakafi mechanism is very validated, so we are not going into completely unknown territory. We think the risk-benefit ratio of using a topical form of JAK is going to be very meaningful,” Hoppenot said.
Sales of Obzelura have grown even though since September 2021, the FDA has required companies marketing the drug and other Janus kinase (JAK) inhibitors indicated for inflammatory conditions to include a black-box warning on their prescribing labels linking the drugs to “serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis.” The black-box directive does not apply to Jakafi since it not indicated for any inflammatory conditions.
“I think most dermatologists are used to using products that have a boxed warning. It’s a class labeling, not specific to Obzelura. It’s not ideal, but it’s not hurting Obzelura,” Hoppenot said. “When you start seeing its efficacy, knowing that it’s topical, the safety issues are very different from what you would get with a systemic drug, and that logic is prevailing.”
Ruxolitinib is protected in the United States by composition of matter and use patents which, including applicable extensions, are set to expire in mid-2028.
Beyond ruxolitinib, Incyte plans in the first half of 2023 to release data from the pivotal AGAVE-201 trial (NCT04710576) evaluating three different doses of the anti-colony-stimulating factor-1 receptor (CSF-1R) monoclonal antibody axatilimab in patients with recurrent or refractory active chronic GVHD who have received at least two prior lines of systemic therapy.
Incyte is co-developing axatilimab with Syndax Pharmaceuticals through an up-to-$602 million exclusive worldwide collaboration and license agreement signed in 2021.
“That’s where we’ll see if it is enough for submission to the FDA,” Hoppenot said. “Medical need is very high in GVHD. It’s a very, very problematic disease. Basically, these patients have been cured from cancer, with their bone marrow transplant, and suddenly, the transplanted cells are attacking their own body, with symptomatic effects that are very, very bad and it is, in many cases, very deadly. It’s something we think we can improve very much.”
“We are looking at combining axatilimab with other drugs, and potentially going and replacing steroids in the first-line setting,” Hoppenot said.
Other pipeline highlights anticipated in 2023:
- Parsaclisb—Incyte is assessing parsaclisib in warm autoimmune hemolytic anemia in a Phase III trial (NCT05073458), whose estimated primary completion date is August 2024.
- Povorcitinib—Incyte expects to release Phase II data in vitiligo in the first half of 2023, and in prurigo nodularis in the second half. Povorcitinib is also being developed to treat hidradenitis suppurativa, for which Incyte agreed to advance the drug into Phase III studies after presenting positive Phase II data at the European Academy of Dermatology and Venereology (EADV) 31st Congress.
- PD-L1 candidates—Incyte is studying INCB99280 and INCB99318 in various solid tumor indications in trials (NCT04242199 and NCT04272034, respectively) set to generate proof of concept data readouts this year.
Incyte expects slower, more stable growth this year after a spurt in 2022 that saw the company add about 250 people to its dermatologic team, as it established a dermatology commercial organization and activities to support the launch of Opzelura for atopic dermatitis. The hiring surge brought the company’s headcount to about 2,400 people, Hoppenot said, from the 2,094 employees on hand at the end of 2021 and 1,773 at the end of 2020, according to the company’s Form 10-K annual report for 2021.
“I believe it’s important to grow not too fast because if you want to maintain a culture, you want to maintain the connection among people,” Hoppenot said. “Many of the things we do at Incyte are done by people picking up the phone, calling somebody, and solving the problem. Things are done and they don’t need to make a memo or send an email.”
Incyte maintains global headquarters in Wilmington, DE, with a European HQ located in Morges, Switzerland, and a large-molecule production facility in Yverdon, Switzerland. The company aims to co-locate within its facilities employees whose jobs do not require them to work outside the office or lab.
“Part of the reason for that is to have unexpected learnings where people meet other people and learn something that they didn’t know before, just by having the opportunity to have lunch together,” Hoppenot added. “This concept of campus to me is very important.”