With FDA’s Eye on JAK Drugs, Concert Pharma Moves One Ahead For Hair Loss

Xconomy Boston — 

Despite the safety concerns that have recently emerged for class of drugs known as JAK inhibitors, their reach continues to grow. The latest example comes from Concert Pharmaceuticals, which is racing the drug giant Pfizer to develop a medicine for a common skin disease that causes hair loss.

Concert (NASDAQ: CNCE) is disclosing this morning that its experimental drug CTP-543 succeeded in a Phase 2 study in 149 patients with alopecia areata—a disease that occurs when the immune system goes haywire and attacks its own hair follicles, causing patches of hair to fall off the scalp, face, and elsewhere. A high (12 mg) daily dose of CTP-543 led to a statistically significant improvement in a measure of hair loss known as a Severity of Alopecia Tool (SALT), compared to placebo, after 24 weeks of treatment, the main goal of the study.

Patients in the study started with an average SALT score of 88 percent: 100 percent indicates total baldness. According to Lexington, MA-based Concert, 58 percent of patients on the high dose of CTP-543 saw at least a 50 percent relative reduction in their SALT scores, compared to 9 percent of placebo patients. (In November 2018, Concert reported 47 percent of medium dose patients hit that mark, and 21 percent of those on a low dose, the latter of which wasn’t statistically significant.)

There are caveats: The long-term effects of CTP-543, a medicine taken for life, aren’t known. Concert CEO Roger Tung says the high dose has a “clear and significant separation from placebo” after 12 weeks; the medium dose took four weeks longer. A rival Pfizer (NYSE: PFE) alopecia areata drug appeared to kick in earlier in its own Phase 2 test, though cross-trial comparisons are tricky. Concert will disclose more detailed results at a future medical meeting, and they’ll be crucial in understanding the magnitude of the drug’s effects and how well it’s being tolerated.

Nonetheless, Tung believes the data are “the strongest seen for a JAK inhibitor—or any other mechanism, for that matter—being developed to treat alopecia areata.”

Concert will begin a Phase 3 trial next year, which is noteworthy because it and Pfizer are angling to become the first company to win FDA approval of a treatment for the disease. And they’re doing so at a time when JAK inhibitors, pills that are being developed for a slew of autoimmune disorders and are marketed for a few of them, have come under increased regulatory scrutiny because of side effects that have cropped up in other studies.

Alopecia areata affects as many as 6.8 million Americans, according to the National Alopecia Areata Foundation. It is the second-leading cause of hair loss, following male-pattern and female-pattern baldness in men and women, respectively, and can lead to other issues like anxiety and depression. There are no drugs approved specifically for the condition, though several immunosuppressive treatments—steroids and otherwise—are used off label to slow down the immune attack. Patients also opt to wear wigs or use hair-regrowth methods like minoxidil or platelet-rich-plasma therapy. Tung counters the medical options have “modest efficacy and poor tolerability.”

Studies over the past several years have shown that JAK inhibitors—which muck with molecular pathways involved in inflammation—might help stifle the immune response and help new hair to grow as well. While topical forms have struggled, pills have shown promise. The most advanced is a drug from Pfizer, PF-06651600, which began a 660-patient Phase 3 study in January. The trial should wrap up in 2021, according to the clinicaltrials.gov database. (ALT-501, from Aclaris Therapeutics (NASDAQ: ACRS), is in the mix as well, but Aclaris plans to sell the drug to another firm).

JAK inhibitors have already become big sellers, chiefly as oral alternatives to injectable medicines for rheumatoid arthritis. Incyte (NASDAQ: INCY) won FDA approval of the first JAK inhibitor, ruxolitinib (Jakafi), for myelofibrosis, in 2011. Since then several have followed, mostly with approvals in rheumatoid arthritis: tofacitinib (Xeljanz, from Pfizer), (Olumiant, from Eli Lilly), and just two weeks ago, upadacitinib (Rinvoq, AbbVie). Others, like filgotinib, from Gilead Sciences, are in development. The field’s top seller, Xeljanz, generated $1.8 billion last year. Rinvoq and others are being tested in a variety of different diseases as well.

But there are concerns about JAK inhibitors. Olumiant came to market in 2018 with a safety warning for blood clots. Similar problems were seen in a post-marketing study of Xeljanz this year, leading the FDA to slap a warning on the drug in July. Upon approving Rinvoq—which had better safety results in human tests—the FDA warned of serious infections, malignancy, and blood clots. This “suggests the FDA now regards these events as class liabilities, regardless of what is reported from pivotal trials,” wrote SVB Leerink analyst Geoffrey Porges in a recent note.

Since most of the safety data accrued for JAK inhibitors has been seen in other diseases, “we do not necessarily see it as being comparable to alopecia areata,” Tung says. “CTP-543 has been associated with a good overall tolerability profile.”

Still, a January editorial published in the journal Lancet sounded alarm bells about the emerging use of JAK inhibitors specifically in alopecia areata, citing their high cost, the broad biological impact they have, and thus, wide range of potential side effects—like severe viral and bacterial infections—they can cause. The “understandable euphoria surrounding JAK inhibitors in the alopecia areata field” thus “might over-encourage their use even in patients in whom it would be ill-advised.” The editors called for a “sober-risk-cost-benefit evaluation” given that the disease isn’t life threatening and JAK inhibitors are “prohibitively expensive.” AbbVie just priced Rinvoq at $59,000 per patient, per year.

Safety, and eventually pricing questions will thus hang over both Concert and Pfizer as they press forward. Pfizer said the most common side effects it saw with PF-06651600 were infections and gastrointestinal issues. Concert said one patient in its CTP-543 study had facial cellulitis, but treatment continued after a “brief interruption.” The rest were mild problems like colds and headache, and all but three patients on its 12 mg dose chose to participate in a long-term safety study, Tung says.

Each of those studies tested the drug over just six months. Longer trials will be more telling. Concert plans to have “multi-year data” on safety by the time it wraps up its Phase 3 program, Tung says.

Photo of alopecia areata courtesy of Thirunavukkarasye-Raveendran via Creative Commons.