Ritlecitinib: an investigational drug for the treatment of moderate to severe alopecia areata

ABSTRACT

Introduction

Alopecia areata (AA) is an inflammatory and autoimmune form of hair loss, which can present with one patch of hair loss, but in more extreme cases can lead to total body hair loss. There are limited therapeutic options and no cure, but medication can sometimes induce sustained remission. Disease control cannot be guaranteed; even those who regrow all hair on treatment can experience relapse. There are no FDA approved systemic treatments; therefore, an unmet need for safe, and effective treatments exists. Few treatments have been evaluated by randomized controlled trials. Case reports and series indicate oral Janus Kinase (JAK) inhibitors as a potential therapy. Ritlecitinib is a novel oral JAK3-selective inhibitor being investigated as an AA treatment.

Areas covered

This article introduces ritlecitinib as treatment for AA and considers the mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety [reporting data from a 24-week, phase 2a double-blinded placebo-controlled trial of ritlecitinib in patients with AA who have more than 50% scalp hair loss].

Expert opinion

Ritlecitinib offers a novel mode of action, rapid onset, and the capacity for a superior safety profile over other JAK inhibitors. If approved, ritlecitinib will be widely prescribed by physicians overseeing the more severe AA patients for the foreseeable future. As JAK inhibitors regulate the hair growth cycle and have anti-inflammatory effects, the implementation of ritlecitinib in hair loss disorders other than AA, may prove beneficial.

KEYWORDS:

• Alopecia areata
• alopecia totalis
• alopecia universalis
• hair diseases
• JAK inhibitors/ janus kinase inhibitors
• JAK 3 and ‘tyrosine kinase expressed in hepatocellular carcinoma’ family inhibitor
• PF-06651600
• ritlecitinib
• safety
• SALT score

Funding

This paper was not funded

Article highlights

• There has been no reliable, effective, and safe therapy for alopecia areata, especially those with severe and chronic disease. There exists an unmet need for effective therapy that is safe and appropriate for long-term use.

• Studies evaluating Janus Kinase (JAK) inhibitors in severe AA have had encouraging results. Ritlecitinib, a novel oral JAK 3 and ‘tyrosine kinase expressed in hepatocellular carcinoma’ family inhibitor has recently been investigated to treat AA.

• Results from a 24-week treatment with ritlecitinib versus placebo have shown it to be effective and well tolerated in patients with severe AA, including those with alopecia totalis and universalis. Treatment with ritlecitinib met the primary end point at 24 weeks, with 50% of patients achieving SALT₃₀ (90% CI, 38–62%) versus 2% of those receiving placebo (90%CI, 0-9%)

• A fast onset of treatment effect was noted and more patients experienced eyelash and eyebrow growth with ritlecitinib than with placebo.

• The significant improvement in the AASIS scores in the ritlecitinib group versus placebo after 24 weeks confirms the unmet need for treatment that will improve symptoms and patient’s quality of life.

• Ongoing studies with ritlecitinib should provide further additional safety data as well as provide data on withdrawal and re-treatment efficacy. Long-term studies are warranted to understand the lifelong safety and impact of ritlecitinib on patients’ health.

Declaration of interest

SE reports being on the Australian dermatology advisory board for Eli Lily. She is/has been principal investigator in clinical trials for AbbVie, Arena Pharmaceuticals, Avance Clinical, Boston Pharmaceuticals, Botanix, Bristol-Myers Squibb, Dermira, Eli Lilly and Company, Jansen, Kobiolabs, LEO Pharma, Novartis, Pfizer Inc., Regeneron, Suzhou Connect Biopharmaceuticals, TEVA pharmaceuticals and Tigermed. She is currently serving as treasurer of the Australasian Hair and Wool Research Society.

RS reports being a member of, on the International advisory board of, and principal investigator in sponsored clinical trials for PfizerAbbvie, Leo Pharmaceuticals, Novartis and Eli Lily. He is founder, director and principal investigator in clinical trial for Samson clinical. He has been/is currently a principal investigator in clinical trials for AbbVie, Aerotech, Akesobio, Amgen, Arcutis, Arena, Ascend AstraZeneca, Bayer AG, Biotherapeutics Boehringer Ingelheim, Bristol Myer Squibb, Celgene, Coherus BioSciences, Connect, Demira, Eli Lilly and Company, Galderma, Glaxo Smith Kline, F. Hoffman–La Roche, Janssen, MedImmune, Merck and Co, Merck Sharpe & Dohme,Novartis, Oncobiologics, Pfizer, Principia, Regeneron, Roche,, Reistone Biopharma, Samson Clinical,, Sanofi-Genzyme, Sun Pharma UCB and Valeant, and is serving as the current President of the Australasian Hair and Wool Research Society

RS was principal investigator and SE was a sub-investigator in clinical trials with ritlecitinib for alopecia areata (ALLEGRO studies)

In accordance with Taylor and Francis policy and my ethical obligation as a researcher, I am reporting that I am a consultant to a company that may be affected by the research reported in the enclosed paper. I have disclosed those interests fully to Taylor and Francis, and I have in place an approved plan for managing any potential conflicts arising from that involvement.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Supplementary material

Supplemental data for this article can be accessed here.