Pfizer's JAK inhibitor clears second pivotal eczema study, but can it topple Regeneron's Dupixent?
The atopic dermatitis market is crowded. Dupixent, from Regeneron and Sanofi, may be king of the arsenal of therapies to combat eczema — but various drugmakers big and small are out to usurp its throne. Pfizer on Friday made its pitch, with a second slate of positive late-stage data on its experimental drug, abrocitinib.
Abrocitinib belongs to a class of drugs called Janus kinase (JAK) inhibitors — which have been plagued with safety concerns. Named after the two-faced Roman God Janus, the family consists of four enzymes: JAK1, JAK2, JAK3 and TYK2, which are associated with cytokine receptors on the surface of cells and form part of a pathway involved in inflammatory and immune responses.
Abrocitinib, a JAK1 inhibitor, is thought to modulate multiple cytokines involved in the pathophysiology of eczema including interleukin (IL)-4, IL-13, IL-31, and interferon gamma. On Friday, the US drugmaker said it had met goals of the 391-patient JADE MONO-2 study, which tested two doses (100mg and 200mg once daily) of the drug against a placebo.
Consistent with the JADE MONO-1 trial, data from this study showed that by week 12 the percentage of patients achieving each co-primary efficacy endpoint, as well as each key secondary endpoint, with either dose of abrocitinib was statistically significantly higher than placebo. In addition, a statistically significant number of patients achieved a reduction in pruritus (severe itching) by week 2, as measured by a four-point or larger reduction in itch severity measured with the pruritus numerical rating scale (NRS).
Detailed data from JADE MONO-1 are expected at a Madrid conference in October, Pfizer $PFE said, adding that results from a trial testing abrocitinib against an active control should readout in spring 2020.
There are various JAK inhibitors on the market approved for a range of immune-mediated diseases. Pfizer already has a JAK1/JAK3 inhibitor — Xeljanz — in its portfolio, although its use has been blighted by regulatory restrictions after the higher dose of the blockbuster drug was found to be associated with the risk of blood clots and death.
Eli Lilly’s $LLY JAK1/JAK2 Olumiant, meanwhile, was initially rejected by the US agency due to safety concerns — only to eventually secure approval for the lower dose. Lilly’s partner, Incyte $INCY, elected to walk away from co-funding the drug’s development as fears about the benefit-risk profile of the class of drugs accumulated. Last month AbbVie’s $ABBV JAK1 upadacitinib was cleared by the FDA for rheumatoid arthritis with a black box warning, a feature analysts expect will be incorporated into the label of Gilead’s $GILD Galapagos-partnered filgotinib, should it secure approval.
In terms of atopic dermatitis specifically, Regeneron $REGN and Sanofi’s $SNY Dupixent (chemically known as dupilumab) was the first biologic to win approval for the condition in 2017, and is now the de-facto leader in the market. It is engineered to inhibit the signaling of IL-4 and IL-13 — two proteins that likely play a key role in the inflammation that underlies eczema and a host of allergic diseases.
“While dupilumab (dupi) has set an extremely high bar in AD, the evolving competitive landscape has not been quite as strong yet. Recent developments serve as important reminders that the ‘crowded’ AD landscape may not look quite as congested once the dust starts to settle and the winners create separation from the rest of the pack,” SVB Leerink analysts wrote in a note in June.
In Pfizer’s JADE MONO-2 study, abrocitinib’s safety profile was less than straightforward. The frequency of treatment-emergent adverse events was higher in treatment arms versus placebo, and one patient with co-existing cardiovascular risk factors died three weeks following the study from unknown etiology — although the drugmaker said the event was not related to abrocitinib.
“While we expect efficacy for abrocitinib to be potentially comparable to Regeneron’s Dupixent, many questions remain whether abrocitinib is safe enough to be a formidable competitor to Dupixent,” Credit Suisse’s Evan Seigerman wrote in a note. “We expect intensifying competition in AD over the next few years from novel JAK inhibitors (abrocitinib, AbbVie’s upadacitinib) and novel biologics (namely targeting IL-13 and 33).”
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