Ritlecitinib

Ritlecitinib will likely benefit from its first-in-class status, rapid onset of action and expected label for both adults and adolescents, potentially providing an effective option to stimulate hair growth in a stigmatizing disease. It is currently the only JAK inhibitor being evaluated for adolescent patients who are the most likely to aggressively seek care for a disorder that profoundly affects their physical appearance.

About ritlecitinib

Pfizer Inc
Janus kinase 3 (JAK3)/TEC inhibitor Daily oral administration to treat alopecia areata
Also being evaluated for vitiligo, Crohn’s disease, ulcerative colitis and, in combination with either tofacitinib or zimlovisertib, rheumatoid arthritis
~4.7 million people with alopecia areata in the United States and top five European markets in 2020

Why is it a drug to watch?

Ritlecitinib is the first in a new class of oral, highly selective kinase inhibitors. It is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3 (JAK3).

The New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and marketing authorization application (MAA) to the European Medicines Agency (EMA) were supported by data from the phase 2B/3, dose-ranging ALLEGRO study in patients 12 years and older with at least 50% scalp hair loss:
• The 30 mg and 50 mg doses resulted in significantly greater proportions of patients with no more than 20% hair loss after six months compared with placebo.
• Ritlecitinib was tolerated well by adults and adolescents.
The phase 3 ALLEGRO-LT study is investigating the drug’s long-term safety and efficacy at the 50 mg dose.

Review and approval status

September 2018:
• Breakthrough Therapy Designation: U.S. FDA

September 2022:
• NDA accepted: U.S. FDA
• MAA accepted: EMA

Expected launch:
• 2023: United States
• 2024: Europe

Patents estimated to expire beginning in 2039

How will ritlecitinib impact the market for alopecia areata?

This large and under-served market is expected to grow to as much as $2.5 billion by 2030 in the United States and the top five European markets (Germany, France, the U.K., Spain and Italy), largely driven by JAK inhibitors. Ritlecitinib’s broad target population and first-in-class status are expected to help it achieve a 2.0% and 1.4% share of drug-treated patients in the United States and the top five European markets, respectively, by 2030.

First-line therapy for nearly all treated, newly diagnosed patients involves topical corticosteroids; when those are insufficient, systemic corticosteroids are used.
Only one therapy is currently approved to treat alopecia areata—Olumiant®, which received U.S. FDA approval and a positive Committee for Medicinal Products for Human Use (CHMP) opinion in 2022—but JAK inhibitors have been used off-label for years.
Despite the class-wide black box warning for serious infections, mortality, malignancy, major adverse cardiovascular events (MACE) and thrombosis, the long history of JAK inhibitor use for other indications has contributed to their use in alopecia areata.
The safety risks outlined in the black box warning have particularly constrained off-label use of JAK inhibitors in pediatric and adolescent patients.
Numerous studies showing the efficacy of JAK inhibitors for hair regrowth has garnered interest in their use.

What gaps in treatment does ritlecitinib fill?

Alopecia areata often causes hair loss at the scalp but can also affect eyebrows, eyelashes, facial hair and other areas, leading to a potentially negative impact on patients’ daily lives and a significant emotional burden. First-line therapy for new diagnoses are topical corticosteroids, which vary in their effectiveness at hair regrowth.

What hurdles might it need to overcome to reach blockbuster status?

Given the existing concerns about safety issues associated with JAK inhibitors, adoption will likely depend on the safety data from the phase 3 ALLEGRO-LT trial. This is especially true given alopecia is primarily a cosmetic disease, for which the benefit will need to outweigh the risk. Competition from other JAK inhibitors in the market or in late-stage development could also limit uptake.

$0.20B

expected sales in 2027

95%

probability of success for ritlecitinib in the United States.

“It is important that adolescent patients are being included in pivotal trials because adolescents are often the patients most profoundly affected by alopecia areata.”