Pfizer's JAK3 Inhibitor PF-06651600 Receives FDA Breakthrough Therapy Designation for Alopecia Areata
VCBeat (WeChat: vcbeat) has learned that on September 5, U.S. time, Pfizer’s orally administeredJanus Kinase 3 (JAK3) InhibitorPF-06651600 Receives FDA Breakthrough Therapy Designation for the Treatment of Patients with Alopecia Areata
Alopecia areata, medically known as "alopecia areata" and colloquially referred to as "ghost shaving," differs from the more common androgenetic alopecia (often called "Mediterranean baldness"). Alopecia areata has a rapid onset; clinically, it presents with irregularly shaped patches of hair loss. In severe cases, patients may lose not only scalp hair but also eyebrows, eyelashes, and axillary hair.
Alopecia areata has been confirmed as an autoimmune disease, characterized by hair loss on the scalp, face, or body, typically in patches. Individuals with alopecia areata experience symptoms when immune cells attack healthy hair follicles, leading to hair loss that usually begins as smooth, circular patches. The average age of onset is between 25 and 35 years, but it can also affect children and adolescents and occurs in both males and females across all ethnic groups.
More than half of patients with alopecia areata experience a poor quality of life; therefore, this condition can lead to severe psychological consequences, including significant depression and anxiety.
The First FDA-Approved Treatment for Alopecia Areata
How to Treat Alopecia Areata? As early as June 2014, promising therapies were identified. Two scientists from Yale University announced that they had cured alopecia universalis using tofacitinib citrate tablets. Subsequently, in August, Dr. Angela Christiano, a renowned hair loss research expert at Columbia University, and her team announced the successful treatment of alopecia areata cases using ruxolitinib, an approved medication for myelofibrosis (marketed under the brand names Jakafi in the United States and Jakavi in the European Union).
In this trial, the team studied three patients, all of whom were cured. The patients received ruxolitinib twice daily, and nearly complete hair regrowth was observed within 4–5 months. Notably, none of the three patients experienced adverse effects. The findings were published in Nature Medicine.
Subsequently, Angela Christiano’s team conducted further trials and studies with an expanded cohort, further confirming the drug’s efficacy. Thereafter, researchers at Stanford University and Yale University also carried out related experimental studies.
In the trial, they used two medications: tofacitinib citrate tablets for arthritis and ruxolitinib for myeloma. Both drugs are JAK (Janus kinase) inhibitors and have demonstrated significant efficacy in treating alopecia universalis, but they are ineffective for common male pattern baldness.
According to available data, Pfizer’s receipt of the FDA Breakthrough Therapy Designation for alopecia areata was based on favorable results from a Phase II study, which will be presented at a press conference during the 27th Congress of the European Academy of Dermatology and Venereology (EADV) in Paris on September 15, 2018.
“Breakthrough Therapy Designation” was established by the U.S. FDA in July 2012, stemming from provisions set forth in the Food and Drug Administration Safety and Innovation Act (FDASIA). It aims to accelerate the development and review of new drugs for treating serious or life-threatening conditions. As another new drug review pathway introduced by the U.S. FDA following Fast Track, Accelerated Approval, and Priority Review, drugs granted “Breakthrough Therapy” designation receive more intensive guidance, including from senior FDA officials, to ensure that new treatment options are made available to patients in the shortest possible time.
By designating PF-06651600 as a breakthrough therapy for alopecia areata, the FDA has undoubtedly provided a significant boost, incentivizing corporate development. The “Breakthrough Therapy” designation also fosters closer communication between regulatory authorities and pharmaceutical companies, thereby facilitating the market launch of urgently needed medications. Furthermore, Pfizer is collaborating with the European Medicines Agency (EMA) on the clinical development plan for PF-06651600.
Development of Multiple Unique Kinase Inhibitor Therapies
Commenting on this breakthrough, Michael Corbo, Chief Development Officer of Inflammation and Immunology at Pfizer Global Product Development, stated, “We are encouraged by the approval of this breakthrough therapy, as it underscores the ability of our JAK3 inhibitor to address critical unmet medical needs. We will continue to work closely with the FDA throughout the development process, with the goal of making this potential new treatment available to patients with alopecia areata as soon as possible.”
Data indicate that JAK inhibitors play a critical role in inflammatory processes, as they are involved in the signaling of more than 50 cytokines and growth factors, many of which drive immune-mediated conditions. “Pfizer is committed to advancing JAK science by developing multiple JAK inhibitors with unique selectivity profiles, which are currently being evaluated in clinical trials. These inhibitors have the potential to address significant unmet needs across a range of inflammatory conditions,” said Michael Vincent, Chief Scientific Officer of Inflammation and Immunology at Pfizer.
Pfizer has established world-leading kinase research capabilities and is developing a variety of unique kinase inhibitor therapies. As a pioneer in JAK science, the company continues to advance several molecular research programs featuring novel selective molecules that, if approved, could provide transformative therapies for patients. In addition to PF-06651600, Pfizer is evaluating the following kinase inhibitors in clinical trials across multiple indications:
1. PF-04965842: A selective JAK1 inhibitor in Phase 3 clinical trials for the treatment of atopic dermatitis (AD). PF-04965842 has received FDA Breakthrough Therapy Designation for the treatment of patients with moderate-to-severe AD;
2. PF-06700841: A tyrosine kinase 2 (TYK2)/JAK1 inhibitor under investigation for the treatment of psoriasis, Crohn's disease, ulcerative colitis, and alopecia areata;
3. PF-06650833: An interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor under investigation for the treatment of rheumatoid arthritis;
4. PF-06826647: A TYK2 inhibitor under investigation for the treatment of psoriasis and inflammatory bowel disease (IBD).
In the history of alopecia drug development, finasteride (Propecia), developed by Merck & Co., is available for male patients and can promote hair regrowth or alleviate hair loss. Finasteride (for treating androgenetic alopecia) and minoxidil (for treating androgenetic alopecia and alopecia areata) are the only two drugs approved by the U.S. FDA for the treatment of hair loss.
Pfizer’s PF-06651600 has been designated as a Breakthrough Therapy, prompting the FDA to accelerate its development and review. It is anticipated that this JAK inhibitor will soon reach the market, benefiting patients with alopecia areata.
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References:
https://www.businesswire.com/news/home/20180905005542/en/Pfizer-Receives-Breakthrough-Therapy-Designation-FDA-PF-06651600
https://www.marketwatch.com/press-release/pfizer-receives-breakthrough-therapy-designation-from-fda-for-pf-06651600-an-oral-jak3-inhibitor-for-the-treatment-of-patients-with-alopecia-areata-2018-09-05