Pfizer is making moves on the dermatology and wider immunology fronts, detailing two phase 3 wins for its oral Janus kinase inhibitor, Litfulo, and a promising phase 2 update for its investigational biologic tilrekimig.
“Our momentum in dermatology is quite strong right now,” said Michael Vincent, M.D., Ph.D., chief inflammation & immunology officer at Pfizer, in an interview. And now that Pfizer's treatment pathways are validated by dermatology wins, presented at the European Academy of Dermatology and Venereology (EADV) annual congress in Vienna, the company is eyeing broader opportunities in immunology beyond skin diseases, Vincent told Fierce.
For its part, Lifulo—an already approved treatment for alopecia areata—significantly improved repigmentation in patients with vitiligo, a chronic autoimmune condition whereby patches of the skin turn white because the immune system mistakenly attacks pigmenting cells called melanocytes.
The findings came from the Tranquillo 2 and Tranquillo phase 3 trials, which tested 100-mg and 50-mg Litfulo doses, respectively, in patients with both active and stable nonsegmental vitiligo. Pfizer posted topline results from the studies back in July but has now dug deeper into the specific numbers behind the Tranquillo success stories.
Of patients taking the 100 mg dose of Litfulo, 21.86% saw a more than 75% improvement on a measure of facial repigmentation and 13.02% saw a greater than 50% improvement in their total body pigmentation compared to 2.4% in both trials' placebo groups.
For those patients that received the 50 mg dose, 12.47% experienced a 75% or better improvement on a measure of facial repigmentation and 8.98% saw a greater than 50% improvement in their total body pigmentation compared to 2.48% and 1.98% in the placebo group.
Both trials reported a meaningful benefit as early as 24 weeks, with an increase through week 36 and week 52. And patients in the treatment arm saw a significant reduction in self-reported facial and overall disease severity and were more likely to rate their vitiligo as “a lot less” or “no longer” noticeable by week 52 compared to placebo, as well.
Critically, both trials showed improvements “in endpoints from physicians as well as patient-reported outcomes,” Vincent told Fierce.
The two trials are the largest phase 3 program to date to evaluate an oral systemic therapy for vitiligo, Pfizer estimates. Earlier this summer, Pfizer said it would take the Tranqillo wins to the FDA in hopes of securing a vitiligo approval. On Friday, the New York pharma affirmed that plan, noting that it will be applying for review with the European Medicines Agency in parallel.
Vitiligo treatment to date has been dominated by Incyte’s Opzelura, a topical cream and the only FDA approved treatment for vitiligo.
“Importantly," said Pfizer's Vincent, "because of systemic absorption and hematological side effects, the quantity of the body surface area that you can use the topical therapy on is limited to a relatively small percentage."
If approved, Litfulo could be the first oral systemic treatment for the condition, but it could face competition from AbbVie’s blockbuster JAK inhibitor Rinvoq sooner than later, too. Rinvoq secured a late summer approval for vitiligo and alopecia areata in the European Union, and its use in nonsegmental vitiligo is currently under review with the FDA. Rinvoq is also taken orally.
At the conference, Pfizer also touted previously-announced phase 2 results for its potential first-in-class trispecific antibody tilrekimig, which targets IL-4, IL-13 and thymic stromal lymphopoietin (TSLP). The New York pharma tested three monthly doses of tilrekimeg against placebo in patients with moderate to severe atopic dermatitis.
The 50 mg, 200 mg, and 400 mg doses all significantly increased in the proportion of patients achieving 75% or more reduction in their eczema severity by week 16 compared to placebo.
“In particular, the two highest levels look very favorable compared to historical standards,” Vincent said, caveating that comparing trials has its limitations.
Atopic dermatitis, or eczema, represents a market of millions of patients. Pfizer already has two approved drugs in the category, topical Eucrisa and oral JAK inhibitor Cibinqo. But the majority of the market is held by Sanofi and Regeneron’s Dupixent.
Early this year, Johnson & Johnson scrapped its own atopic dermatitis candidate after concluding the therapy was unlikely to outperform Dupixent in a head-to-head trial.
Based on the phase 2 tilrekimig readout, Pfizer may have more to offer, Vincent said: “We feel the data suggests there is potential to raise the bar beyond the current standard of care.”
Pfizer’s phase 3 in atopic dermatitis is already underway.
The recent wins have also prompted Pfizer to test its inflammatory portfolio’s limits beyond dermatology.
“We moved decisively into respiratory indications given the validation of these pathways,” Vincent told Fierce. The New York pharma launched a tilrekimig phase 3 in asthma and a phase 2b/3 in COPD earlier this year.