Incyte scores much needed PhIII success — and of course it’s delivered by ruxolitinib
Incyte’s efforts to breathe a second life into ruxolitinib — its JAK inhibitor sold in pill form as Jakafi — has been greeted with clear, if preliminary and unsurprising, Phase III success.
Topline data from the TRuE-AD2 cements ruxolitinib’s foundational importance for Incyte, and gives analysts hope that there might yet be room for growth in a pipeline that’s suffered multiple R&D setbacks.
Comparing two doses of topical ruxolitinib to a placebo cream, researchers found that “significantly more patients” with atopic dermatitis on the drug arms (0.75% and 1.5%, respectively) achieved treatment success as defined by the investigator’s global assessment score, or IGA score, of 0 or 1. To qualify, patients would also have to see at least a two-point improvement from baseline at Week 8.
That’s as much detail as we’re going to get until the biotech presents at a conference. The precise numbers on that primary endpoint, as well as the slate of secondary measures including multiple variations of the Eczema Area and Severity Index (EASI), will have to wait.
Also coming later this quarter: results from a second pivotal study dubbed TRuE-AD1. Together the program enrolled 1,200 patients, who will be followed for up to a year for long-term safety and effectiveness.
Incyte positioned the drug as an alternative to corticosteroids — the standard of care — and a safe option in mild-to-moderate AD.
“Within mild-moderate disease, a proportion of patients are not well controlled on TCS/TCIs, and / or are not eligible for steroids because of disease on the face,” the company wrote in an email to Endpoints News. “In addition, the majority of patients seeking treatment for AD in a dermatologists office have tried TCS previously (many have tried multiple different ones).”
However, Evan Seigerman of Credit Suisse noted that the trial “was not designed to show relatively efficacy to SoC of topical corticosteroids, which could limit its use among dermatologists.”
That said, Incyte does have some comparator data going for it, Cowen analysts wrote when it unveiled Phase II data last June. Dropping in on presentations at the World Derm conference, they saw that lack of reference to established treatments indeed turned out to be a problem for Pfizer’s Eucrisa.
“This has been cited as a hindrance to adoption in addition to its modest efficacy (31-33% IGA response at week 8) and association with application site pain,” they wrote.
In contrast, 1.5% ruxolitinib cream, applied twice daily, was directionally superior to the steroid triamcinolone at week 4 on EASI (72% vs. 60%) and IGA (38% vs. 26%).
And for those who see AD and think Dupixent, Seigerman pointed out that ruxolitinib targets a different patient population with less severe disease.
“We agree with the scientific rationale for using topical ruxolitinib in AD, and would expect that the topical administration would more likely to limit serious side effects more common with systemic treatments,” he wrote.
He estimates that the topical formulation, which is slated for a 2020 NDA submission and 2021 launch, could add $300 million in US sales for Incyte by 2025. Andrew Berens at SVB Leerink pegged peaks for topical ruxolitinib at $1.1 billion.
Incyte’s top team, led by CEO Hervé Hoppenot, is holding onto every dollar and optimistic sentiment around the cash cow franchise to buy time for some R&D reinvigoration. The IDO disaster with epacadostat and the recent Phase III flop with itacitinib blew a huge hole in the late-stage pipeline that the biotech has now filled partly with MorphoSys’ CD19-targeted tafasitamab. It cost $900 million in cash.
There’s more work going on with Jakafi in chronic graft versus host disease, among other projects (the other mid-stage prospects target FGFR1/2/3 and PI3Kδ, respectively).
“We are most interested in the data from the TRuE-V trials of topical rux. in vitiligo (given the higher unmet medical need and lack of treatment options), not expected to read out until 2021,” Seigerman wrote.
Until then the upside is relatively modest, he predicted. Incyte shares $INCY are up 2.14% to $77.7.