Pfizer bows out of the Tyk2 race

2021 had once looked like the year of the Tyk2 inhibitors, but some shine is coming off this member of the Jak family. Pfizer today disclosed plans to offload two projects with activity against Tyk2, not long after the lead proponent of this approach, Bristol Myers Squibb, reported disappointing data with deucravacitinib in ulcerative colitis. Pfizer did not give a reason for its Tyk2 exit, which will see brepocitinib and PF-06826647 licensed to a new company that Pfizer is forming in partnership with an unnamed autoimmune player; the pharma giant will have a 25% stake in this venture and retain certain ex-US rights. Perhaps the decision was spurred by toxicity concerns with the Jak inhibitors, which solidified in September into a class warning; however, Pfizer is keeping hold of its Jak1 abrocitinib – which is still awaiting an FDA decision in atopic dermatitis – and the Jak3/Tec inhibitor ritlecitinib. Still, other mechanisms now look like a priority: Pfizer highlighted several immunology projects in its third-quarter presentation, including a “high potency” topical PDE4 inhibitor, PF-07038124, for atopic dermatitis and psoriasis; PF-06480605, a TL1A inhibitor for ulcerative colitis; and the interferon-beta Inhibitor PF-06823859 in dermatomyositis.

What's in and what's out: Pfizer's Jak family focus
Project Mechanism Indication(s) Status  2026e sales ($m)
Out…
PF-06826647 Tyk2 inhibitor Psoriasis Ph2 (NCT03895372), hit at higher doses 320
Hidradenitis suppurativa Ph2 (NCT04092452) ends Jan 2022 (also includes brepocitinib & PF-06650833 arms)
Oral brepocitinib (PF-06700841) Jak1/Tyk2 inhibitor Psoriatic arthritis Ph2 (NCT03963401), hit at higher doses 143
Vitiligo  Ph2 (NCT03715829) ended Feb 2021 (also includes ritlecitinib arm)
Ulcerative colitis Ph2 (NCT02958865) ended May 2021 (also includes ritlecitinib arm)
Hidradenitis suppurativa  Ph2 (NCT04092452) ends Jan 2022 (also includes PF-06826647 & PF-06650833 arms)
Systemic lupus erythematosus Ph2 (NCT03845517) ends Aug 2023
Crohn's disease Ph2 (NCT03395184) ends Mar 2024 (also includes ritlecitinib arm)
Topical brepocitinib (PF-06700841) Atopic dermatitis  Ph2 (NCT03903822), hit at higher doses
  Psoriasis Ph2 (NCT03850483) ended Apr 2021
Still in…
Cibinqo (abrocitinib) Jak1 inhibitor Atopic dermatitis  EU positive CHMP opinion, awaiting US FDA decision 1,035
Ritlecitinib (PF-06651600) JAK3/Tec Inhibitor Alopecia areata Ph2/3 Allegro (NCT03732807) hit 254
Vitiligo  Ph2 (NCT03715829) ended Feb 2021 (also includes brepocitinib arm)
Ulcerative colitis Ph2 (NCT02958865) ended May 2021 (also includes brepocitinib arm)
Rheumatoid arthritis Ph2 (NCT04413617) ends Feb 2022 (also includes PF-06650833 (Irak-4 inhibitor) & Xeljanz arms)
Crohn's disease Ph2 (NCT03395184) ends Mar 2024 (also includes brepocitinib arm)
Source: Evaluate Pharma & clinicaltrials.gov.

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