Pfizer Eyes First-To-Market Opportunity In Alopecia

Inflammation and Immunology Chief Scientific Officer Michael Vincent talked to Scrip about the first positive Phase II data testing a JAK inhibitor for hair loss caused by alopecia areata, next steps for development and the broader I&I portfolio.

Pfizer Inc. has an opportunity to be first-to-market with a drug for alopecia areata (AA), an autoimmune disease characterized by hair loss and often associated with psychological consequences. The company is advancing an oral Janus kinase (JAK) 3 inhibitor into a Phase IIb/III trial within months, now that the drug has shown a statistically significant efficacy benefit in a Phase IIa study.

The Phase IIa data mark a drug development breakthrough for treating AA, a disease in which immune cells attack healthy hair follicles for which there are no approved drugs. "There have not been any prior placebo-controlled studies in alopecia with oral kinase inhibitors or really any modern therapies," Senior VP and Chief Scientific Officer, Pfizer Inflammation and Immunology Michael Vincent said in an interview.

Pfizer tested two drugs in the Phase IIa trial versus placebo: the JAK3 inhibitor PF-06651600 and a tyrosine kinase (TYK) 2/JAK1 inhibitor PF-06700841. Both drugs significantly improved hair regrowth on the scalp relative to baseline, but while the TYK/JAK1 inhibitor appeared to have an efficacy advantage, Pfizer has decided to move forward with the JAK 3 inhibitor.

Notable Efficacy Results

"Both drugs worked strikingly well," Vincent said. Although numerically, the TYK2/JAK1 inhibitor had an edge on several metrics, he said the totality of the data led the company to select the JAK3 inhibitor. "For this particular indication, the benefit/risk profile looked most favorable for the JAK3 program." The drug has been granted breakthrough therapy designation from FDA for AA.  (Also see "US FDA’s Latest Breakthrough Therapy Awards Include Asthma, Alopecia Areata, And (Of Course) Oncology Therapies" - Pink Sheet, 10 Sep, 2018.) 

 The primary efficacy endpoint of the trial was improvement in hair regrowth on the scalp relative to baseline at week 24 as measured by the Severity of Alopecia Tool (SALT) score, a 100-point scale that is used as a standard measure for AA. Patients with partial and full loss of eyelash and eyebrow hair saw a significant improvement in hair regrowth. Other secondary endpoints and safety were also measured. The data were presented at the European Academy of Dermatology and Venereology meeting in Paris, France Sept. 15.

The study enrolled 142 moderate to severe AA patients who were randomized to receive '600, '841 or placebo. Improvements in the SALT score at 24 weeks was 33.6 points and 49.5 points for the JAK3 and TYK2/JAK1, respectively. Some patients with complete hair loss saw 90% and 100% improvements, Vincent added. Patients also responded rapidly to treatment, with improvements occurring within four to six weeks.

Adverse event rates were comparable between treatment groups, with the most common adverse events being related to infections, gastrointestinal and skin/subcutaneous tissue categories.

The next phase of development will be a Phase IIb/III study that will incorporate some dose-ranging components. The Phase IIa trial was not a dose-finding study and was intended as an initial exploration of the potency of the drugs for AA. The JAK3 inhibitor is also in Phase II development for rheumatoid arthritis, Crohn's disease and ulcerative colitis.

More To Learn About Alopecia Areata

AA is an autoimmune disease that affects millions of people, though the prevalence is not well characterized, particularly for the moderate-to-severe patient population that Pfizer expects to target. The disease can affect people in their youth, with the main age of onset being 25 to 35 years old, and can result in depression and anxiety.

"We are doing some work to better understand this population," Vincent said. "It's not always just the extent of the disease that is impactful. Fundamentally, the impact on patients of this disease is predominantly psycho-social." The impact can also depend on the visible manifestation of the hair loss and the level of involvement. It can impact eyebrows and eyelashes.

Pfizer is looking at methods to collect data on some of the more social and psychological benefits of treatment. Pfizer measured various patient-reported outcomes in the Phase IIa trial, which it plans to report out at a future medical meeting, but Vincent noted that a validated patient-reported outcomes method for AA doesn't exist. The company is working to develop better validated tools to measure those kinds of outcomes.

"At this time, the state of the instruments is not to the degree that you would see with many diseases that are studied," he added.

Building A Robust Portfolio

Pfizer has been a leader in the JAK space, with the 2012 FDA approval of Xeljanz (tofacitinib) for rheumatoid arthritis. Xeljanz, a JAK1/3 inhibitor, was the first JAK inhibitor on the market and has had a long monopoly in the space. It grew slowly into a blockbuster, despite slow uptake initially, gaining indications in psoriatic arthritis and ulcerative colitis more recently. (Also see "Pfizer's Xeljanz: The Slow Road To Blockbuster Status" - Scrip, 4 May, 2017.)

Now Pfizer is aiming to maintain its leadership position in the space with more selective JAK inhibitors, as rivals look to enter the market. Eli Lilly & Co..'s JAK1/2 inhibitor Olumiant (baricitinib) was approved by FDA in June, but the agency only approved a lower dose of the drug that could present competitive challenges.
(Also see "Lilly Prices Olumiant For JAK Battle, But Misses Approval For Higher Dose" - Scrip, 2 Jun, 2018.) Other drug makers are also looking to get into the space, including AbbVie Inc. and Gilead Sciences Inc.

Pfizer has a whole portfolio of JAK inhibitors in clinical development in a range of indications. (Also see "Pfizer Assembling New Commercial Team For Move Into Dermatology" - Scrip, 19 Oct, 2016.) The company plans to continue development of '841 in psoriatic arthritis, Crohn's disease and ulcerative colitis. A selective JAK1 inhibitor is in Phase III trials for atopic dermatitis. In addition, the company is developing a TYK2 inhibitor for psoriatic arthritis and inflammatory bowel disease.

Bristol-Myers Squibb Co. is developing a TYK2 inhibitor in Phase III for psoriasis and got a lot of attention with positive Phase II data presented at the EADV Congress showing what it called "biologic-like efficacy" with a safe profile in patients with psoriasis. (Also see "Bristol Engineers An Oral TYK2 Inhibitor With Biologic-Like Efficacy That Rivals JAK Safety" - Scrip, 12 Sep, 2018.) 

Pfizer's TYK2 inhibitor is in Phase I testing for psoriatic arthritis and inflammatory bowel disease.

As Pfizer looks to bring new drugs to market from its Inflammation and Immunology portfolio, Vincent said the company is focused on developing molecules that have unique selective profiles, which he says will bring unique benefit/risk profiles to the market.

"We feel we have as deep and as broad a pipeline in this area as anyone, if not better," Vincent said. "We think our history in this area positions us very well to make the best choices about how to target these selective agents to the best patient population."