Concert’s CTP-543 Shows Advantages Over Lilly, Pfizer Candidates For Alopecia
Executive Summary
Concert’s deuterated ruxolitinib analog is potentially third in line to market for alopecia areata, behind Lilly’s Olumiant and a Pfizer JAK3 inhibitor, but may be demonstrating a best-in-class profile.
On the heels of confirmation of its intellectual property over its JAK1/2 inhibitor CTP-543, Concert Pharmaceuticals, Inc. now has a successful Phase III study that could position it to have a best-in-class profile in alopecia areata. The drug is likely to reach market after big pharma rivals Eli Lilly and Company and Pfizer Inc., but the pivotal data indicate advantages that could help it catch up, according to analysts.
Concert announced on 23 May that CTP-543, a deuterated formulation of Lilly/Incyte Corporation’s JAK inhibitor Jakafi (ruxolitinib), met the primary endpoint of scalp-hair regrowth in alopecia patients with at least 50% hair loss in the 706-patient, placebo-controlled THRIVE-AA1 study. The Lexington, MA-based firm expects to report data from a second pivotal trial, THRIVE-AA2, during the third quarter and potentially submit a new drug application for CTP-543 during the first half of 2023. (Also see "Wild Ride For Immunology? New Mechanisms, Big Indications Up For US FDA Approval In 2022" - Pink Sheet, 8 Feb, 2022.)
On 11 May, the US Patent Trial and Appeal Board (PTAB) upheld Concert’s claims to its patents covering CTP-543, denying patent-infringement allegations by Incyte. Concert has asserted that CTP-543 is a new molecular entity; with the PTAB decision, it appears to have intellectual property rights for the compound into 2037, according to a 12 May analysis by JMP Securities’ Jason Butler. (Also see "Concert Says Phase II Alopecia Drug Could Beat Pfizer’s Candidate To Market" - Scrip, 4 Mar, 2019.)
Concert said 8mg and 12mg doses of CTP-543 both met the primary endpoint of achieving a Severity of Alopecia Tool (SALT) score of 20 or lower at week 24 of treatment, with 41.5% of patients in the 12mg arm and 29.6% in the 8mg arm compared to 0.8% in the placebo arm. Concert’s chief development officer James Cassella told Scrip that the company intends to continue moving forward with both doses of the drug.
SALT measures the portion of scalp without hair due to alopecia; a score of 20 or less means that 80% or greater scalp hair coverage. The drug also met key secondary endpoints in the study, Concert said, including a Hair Satisfaction Patient Reported Outcome measure and evaluations of the primary endpoint at weeks 8, 12, 16 and 20.
CTP-543 was generally well tolerated, the company added, with no cases of pulmonary embolism or deep vein thrombosis – two prominent safety concerns about oral JAK inhibitors – seen in THRIVE-AA1. Adverse events occurring in 5% or greater of study participants were headache, acne, upper respiratory infection, increased creatinine kinase levels, COVID-19 infection and nasopharyngitis. In the case of upper respiratory infections, rates were higher in the placebo arm than in either study-drug dosing arm, Concert added.
Best-In-Class Profile Possible In Competition With Lilly, Pfizer
Multiple analysts said the THRIVE-AA1 data indicate a best-in-class profile for CTP-543 compared to two other Phase III JAK inhibitors for alopecia – Lilly’s Olumiant (baricitinib), which Incyte originally developed as a follow-on JAK1/2 inhibitor to ruxolitinib, and Pfizer’s JAK3 inhibitor ritlecitinib. Olumiant is already under review at the FDA for an alopecia indication with an August user fee date, while ritlecitinib hit its primary endpoint in the Phase II/III ALLEGRO study in alopecia in August 2021. (Also see "Top Five Takeaways From World's Largest Dermatology Conference" - Scrip, 29 Mar, 2022.)
Baricitinib yielded response rates of between 11% and 35% on SALT <20 at 24 and 36 weeks in Phase III studies, while a 30mg dose of ritlecitinib produced a 22% response rate and a 50mg dose yielded a 31% response rate at 24 weeks, noted JMP analyst Butler in a 23 May note. He said the data from THRIVE-AA1 compare favorably to the results of the Lilly and Pfizer alopecia studies in both magnitude and speed of response. The data also de-risk the pending THRIVE-AA2 trial, he asserted.
“The treatment effect was achieved as early as eight weeks with statistical significance, which we view as an important differentiating attribute, and continued to improve through the full 24-week randomized period with no evidence of plateau,” noted Butler. Results to date from an open-label extension of Concert’s successful Phase IIb study of CTP-543 suggest the drug’s effect may also improve with time, he added.
Mizuho Securities analyst Vamil Divan offered similar praise for the Concert data, which he called “highly positive” and indicative of a best-in-class risk-benefit profile. Lilly and Pfizer, however, are likely to reach market before Concert, already have substantial and deep-pocketed commercial organizations, and their alopecia candidates are dosed once daily, while CTP-543 needs to be taken twice a day, the analyst said in a 23 May note.
“However, there is a significant unmet need in alopecia areata and dermatologists we have spoken to previously have mentioned that the product that delivers the most efficacy will likely be the one they end up prescribing the most for their patients,” Divan pointed out.
Divan projects peak sales of CTP-543 in the $800m range, while H.C. Wainwright analyst Andrew Fein called the candidate a potential blockbuster by 2030 with the possibility of capturing 35% market share in alopecia. In his same-day note, Fein stressed that CTP-543’s effect at eight weeks of treatment was a benefit not seen in Lilly or Pfizer’s Phase III clinical trials.
“We believe we have a highly competitive profile,” Concert’s Cassella told Scrip, adding that the clinical-stage biotech is planning on marketing CTP-543 on its own in the US. He did not reply to questions about Concert’s ex-US plans for the drug.
Concert recently went all-in on its prospects in alopecia, offloading much of its pipeline to Terran Biosciences at undisclosed financial terms on 11 March. (Also see "Deal Watch: AbbVie Partners With Gedeon Richter In Neuropsychiatry" - Scrip, 18 Mar, 2022.) Although Concert’s share price surged in pre-market trading on 23 May, the stock closed the day down nearly 9% to $4.10 per share.