Pfizer's Next-Gen JAK Inhibitor Abrocitinib Shows Positive Phase III Results in Moderate-to-Severe Atopic Dermatitis

Authors: Xu Guanyu, Li Minhua

On May 15, Pfizer disclosed that its next-generation Janus kinase (JAK) inhibitor abrocitinib (code name PF-04965842), which has been designated as a breakthrough therapy by the U.S. Food and Drug Administration (FDA), met all co-primary and key secondary endpoints in a late-stage study involving patients aged 12 years and older with moderate-to-severe eczema.

Significant Clinical Efficacy

This Phase III trial enrolled 387 patients with moderate-to-severe atopic dermatitis, who were randomized to receive either placebo or oral abrocitinib at a daily dose of 100 mg or 200 mg. After 12 weeks, the treatment groups demonstrated superior efficacy compared to placebo in achieving almost clear or completely clear skin.

The trial met the primary endpoint requirements, namely an Investigator Global Assessment (IGA) score of clear or almost clear skin, with an improvement of ≥2 points. The Eczema Area and Severity Index (EASI) score showed a reduction of at least 75% from baseline.

The key secondary endpoint was the proportion of patients with a reduction in pruritus severity of ≥4 points, as measured by the Pruritus Numerical Rating Scale (NRS) and the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD).

Furthermore, the benefits of this drug become apparent within two to four weeks after the first dose.

This trial marks the first study in the drug’s development program for atopic dermatitis, with data from another study expected to be released later this year.

Safety Data

Beyond efficacy, drug safety is also paramount. The pharmaceutical giant is well aware of JAK inhibitors and their associated safety concerns. Its earlier product, Xeljanz (tofacitinib), served as a cautionary tale for Pfizer. As the first JAK inhibitor approved by the FDA in 2012, Xeljanz was clearly positioned as a blockbuster drug. However, a post-marketing study earlier this year revealed safety issues, specifically an increased cardiovascular risk associated with high-dose regimens in the treatment of rheumatoid arthritis, raising serious concerns. Following observations of an increased incidence of pulmonary embolism, Pfizer was compelled to discontinue the high-dose treatment regimen.

Pfizer did not disclose detailed data on abrocitinib this time. Although fewer patients in the treatment group discontinued therapy due to side effects compared with the placebo group, the only data provided showed that the proportions of patients who discontinued treatment due to adverse events were 5.8% in the low-dose and high-dose abrocitinib groups, versus 9.1% in the placebo group. This suggests a favorable safety profile. However, Pfizer evidently still has potential concerns.

Market Expectations

Pfizer aims for abrocitinib to become one of the new drugs or indication programs that ultimately achieve blockbuster status by 2022. Now, these positive Phase III results bring it closer to challenging Sanofi and Regeneron’s Dupixent (dupilumab). Pfizer stated that further data will be presented at scientific conferences and published in medical journals.

Dupixent is an effective medication for atopic dermatitis, but it is administered via injection, whereas patients generally prefer oral medications.

Dupixent ushered in a new era for moderate-to-severe atopic dermatitis in 2017, when it became the first approved biologic for this indication, and has recently gained approval to expand its use to adolescent patients aged 12 years and older. In the first quarter of this year, the drug generated €329 million ($368 million) in sales. This figure includes contributions from its new asthma indication, although there remains significant growth potential in the eczema market. Approximately two years after its launch, Sanofi still considers itself “in the early stages” of the adult atopic dermatitis market, with 50,000 patients using the drug in the United States—a small fraction of the total population of 300,000. The opportunity in adolescent atopic dermatitis is approximately half this size.

The new generation of JAK inhibitors, led by AbbVie’s upadacitinib and Gilead’s filgotinib, aims to avoid these pitfalls by improving safety profiles. The FDA’s regulatory decision on upadacitinib later this year will mark the first test for JAK inhibitors since issues were identified with Xeljanz.

The JAK inhibitor market is a focal point for capital markets. According to Cantor Fitzgerald, a financial institution that integrates investment banking and brokerage services, the cumulative sales of this drug class are projected to exceed $20 billion by 2026. Although arthritis remains the primary indication, atopic dermatitis will play a supportive role in realizing commercial benefits. Analysts at Credit Suisse concur with this view. Based on their recent analysis of the overall immunology market, atopic dermatitis is far from saturated, presenting an additional growth opportunity worth $7 billion.

For Pfizer, abrocitinib is merely one experimental asset in its kinase inhibitor portfolio. The pharmaceutical company is also developing a TYK2/JAK1 inhibitor (PF-06700841), an IRAK4 inhibitor (PF-06650833), a TYK2 inhibitor (PF-06700841), and an oral JAK3 inhibitor (PF-06651600).

Original Title: Positive Clinical Results for Pfizer’s Next-Generation JAK Inhibitor Abrocitinib May Propel It to Blockbuster Status!