Concert Says Phase II Alopecia Drug Could Beat Pfizer’s Candidate To Market

Concert Pharmaceuticals Inc. believes it may be positioned to move ahead of Pfizer Inc. in the race to bring the first drug for alopecia areata to market, but the biotech also must stave off a patent challenge from Incyte Corp. regarding its rights to bring a deuterium-modified version of ruxolitinib to market.

Concert presented Phase IIa data for CTP-543, its deuterated formulation of Incyte and Novartis AG’s myelofibrosis drug Jakafi, dosed at 8 mg twice-daily for 24 weeks in patients with alopecia areata at the American Academy of Dermatology (AAD) annual meeting March 2. The drug demonstrated statistically significant hair growth compared to placebo based on the number of patients who showed a 50% or greater improvement in Severity of Alopecia Tool (SALT) score from baseline.

In an interview, Concert CEO Roger Tung said his company has pretty much determined the minimally effective dose of its drug, which is an important factor considering the US FDA’s emphasis on correctly balancing the safety and efficacy of Janus kinase inhibitors. CTP-543 is an oral, selective inhibitor of JAK1 and JAK2, while Pfizer’s PF-06651600 is a selective JAK3 inhibitor. Although CTP-543 is a reformulation of ruxolitinib, it is expected to be considered a new molecular entity (NME).

Pfizer moved its drug into the pivotal ALLEGRO study last September, but Tung believes the pharma will need to conduct an additional confirmatory study in order to file PF-06651600 for approval due to the FDA’s safety emphasis in the JAK inhibitor class.

Concert expects to complete its dose-ranging work with CTP-543 before the end of 2019, which should mean it can initiate pivotal Phase III work in 2020, he explained.

“Pfizer has demonstrated that they have a compound, a JAK3 selective inhibitor, which shows efficacy against AA, however they’ve only studied it in a single dosing regimen,” Tung told Scrip. “They started [Phase II] with a loading dose of the compound for a 28-day period and then backed off to one-quarter of that loading dose for the ensuing five months of that study.”

Complex Study Will Need Time To Find Best Dose

Pfizer’s ALLEGRO study is investigating seven arms – some with induction doses followed by maintenance doses of PF-06651600 and others only testing a maintenance dose. The study is expected to report out data in 2021. Of note, Pfizer obtained breakthrough therapy designation for the drug in alopecia areata – an unmet medical need – last September. (Also see "US FDA’s Latest Breakthrough Therapy Awards Include Asthma, Alopecia Areata, And (Of Course) Oncology Therapies" - Pink Sheet, 10 Sep, 2018.)

“What [the trial design] really indicates is that they don’t know how to use the drug yet,” Tung asserted. “They know there’s activity there, but they don’t know where or how they will get to understand the minimally effective dose.” Because of that, he believes Pfizer will be required to run a confirmatory Phase III trial with an as-yet undetermined dose of PF-06651600, which “gives us a substantial time advantage compared to Pfizer.”

While continuing its clinical development program with CTP-543, however, Concert also will need to deal with a patent challenge from Incyte. The US Patent Trial and Appeal Board has granted Incyte a rehearing on the issue, which will occur on or before April 9, the outcome of which will determine CTP-543’s revenue tail, JMP Securities analyst Liisa Bayko said in a Feb. 14 note. Concert intends to pursue continued development of the drug no matter the hearing’s outcome, but Incyte claims a broad patent on ruxolitinib including deuterated forms of the molecule.

“The question remains whether CTP-543 can be commercialized without any obligations to Incyte,” Bayko said. “At this point, it is difficult to predict a winner one way or the other given the multiple iterations involved, but [Concert] management has committed to its development regardless of the outcome, as the compound would, at a minimum, have five years of exclusivity as a new chemical entity (NCE), enough time to make it a commercially viable opportunity.”

Technology’s Potential Illustrated By Vertex Deal

Concert’s business model, based on creating deuterium-modified versions of already approved drugs, already has proven lucrative, as it obtained $160m up front from Vertex Pharmaceuticals Inc. in 2017 for its deuterated version of ivacaftor, the active ingredient in Vertex’s cystic fibrosis drug Kalydeco and several combination therapies for CF. [See Deal] 

When the deal was struck in March 2017, Vertex generally was viewed as having played defense to protect its CF franchise. (Also see "Vertex Plays Defense In CF With Concert Deal" - Scrip, 6 Mar, 2017.) At the time, Tung told Scrip that Concert planned to keep other candidates from its Deuterium Chemical Entity (DCE) platform in-house by developing outside the approved indications for their original formulations, citing CTP-543 specifically.

Tung said the DCE platform can alter the therapeutic characteristics of a drug, making it efficacious at smaller doses and/or providing a longer half-life. The technology was able to achieve both of those ends with deuterated ivacaftor.

Concert is also working to bring D-serine into human studies for the first time with a deuterated version that may address the amino acid’s renal toxicity issues. Previous attempts to make a D-serine-based drug have ended in preclinical testing due to toxicity, but Concert thinks its formulation could other a new therapeutic option in neuropsychiatric diseases, such as schizophrenia.

The Phase IIa work with CTP-543 continues, as Concert expects to report out data from a 12 mg twice-daily cohort in the third quarter. It is also in the process of initiating a study to compare the safety and efficacy of 8 mg twice-daily – which the company believes is an approvable dosage – against that of 16 mg once-daily, with data expected this year.

“By the end of the year, we hope to understand the dose range with respect to what we could take forward and we also will have a lot more information regarding the dosing characteristics in terms of once- versus twice-daily,” Tung said.

Bayko thinks demonstrating a once-daily dosing capability would only add to CTP-543’s commercial potential. “This makes sense as it gives the company another option to potentially take into a Phase III study with the added benefit of being a more patient-friendly regimen with reduced dosing frequency,” she said.