Deucravacitinib

Approvals in Europe and Japan are expected to follow on the heels of the U.S. Food and Drug Administration (FDA) approval for deucravacitinib in September 2022. As a novel oral, targeted agent that selectively inhibits tyrosine kinase 2 (TYK2), a Janus kinase (JAK) family member that mediates cytokine-driven immune and inflammatory signals, it has the potential to fill a gap in the treatment armamentarium for plaque psoriasis. In addition to its impact for these patients, it is being evaluated for other indications that could benefit more patient populations and boost overall sales.

About deucravacitinib

Bristol Myers Squibb
Allosteric TYK2 inhibitor
Once-daily oral administration to treat moderate-to-severe plaque psoriasis
Also being investigated to treat pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, systemic lupus erythematosus and inflammatory bowel disease
~11.7 million symptomatic psoriasis cases in the G7 markets in 2021
45 years - average age of symptomatic psoriasis cases

Why is it a drug to watch?

Deucravacitinib is a first-in-class oral TYK2 inhibitor with a unique mechanism of action that inhibits signaling of IL-23, IL-12 and type 1 interferon (IFN), key cytokines involved in the pathogenesis of the multiple immune-mediated diseases for which deucravacitinib is being evaluated.

U.S. FDA approval was supported by results from two phase 3 trials, POETYK PSO-1 (deucravacitinib vs placebo) and POETYK PSO-2 (deucravacitinib vs twice-daily apremilast/Otezla®), with adults with moderate-to-severe plaque psoriasis in the United States, Europe and Japan, which showed:

superior skin clearance of once-daily deucravacitinib at both 16 and 24 weeks, measured by Psoriasis Area Severity Index (PASI) 75 response and static Physician's Global Assessment (sPGA) 0/1;
sustained response with deucravacitinib at 52 weeks; and
a safety profile consistent with that noted in phase 2 trials.

Review and approval status

November 2021:
• NDA accepted: U.S. FDA
• Marketing authorization application (MAA) validated: European Medicines Agency (EMA)

December 2021:
• New Drug Application (NDA) submission: Japan’s Ministry of Health, Labour and Welfare (MLHW)

September 2022:
For patients with moderate to severe psoriasis who are candidates for systemic therapy or phototherapy:
• Approved: U.S. FDA, MHLW

November 2022:
• Launch: Japan

Expected launch:
• 2022: United States
• 2023: Europe

Patents estimated to expire beginning in 2033

How will deucravacitinib impact the market for plaque psoriasis?

Uptake of deucravacitinib could be bolstered by its:

oral administration with an efficacy that can compete with that of biologics, which might encourage use in patients who are failing on current oral agents and/or phototherapy, and
superior efficacy over apremliast, which could result in first-line use or for patients who are refractory or intolerant to apremilast, specially since physicians do not consider apremilast to be very efficacious.

Avoidance of a black box warning is positive for other TYK2 drugs currently in development.

What gaps in treatment does deucravacitinib fill?

For symptomatic patients with moderate-to-severe plaque psoriasis, safe, efficacious oral therapies remain an unmet need. Physicians and patients alike prefer the convenience of oral agents over the administration of subcutaneous therapies via injection pen. However, oral systemic drugs often have safety concerns such as renal impairment, hypertension, malignancy and teratogenicity that limit their long-term use. In addition, the currently available oral targeted therapy, apremilast, is not as effective as available biologics, a gap that could be filled by deucravacitinib.

What hurdles might it need to overcome to reach blockbuster status?

Although extra regulatory scrutiny on the safety profile of deucravacitinib was expected given that a previous oral therapy, tofacitinib, that targeted close parallel pathways (JAK1 and JAK3) was turned down by both the FDA and EMA based on its safety data, deucravacitinb avoided a black box label and was approved by the U.S. FDA. Despite some potential mild trepidation by prescribers initially, experts expect that deucravacitinib’s efficacy and tolerability data will set it apart. It will compete with Otezla, which does not require the same level of monitoring as deucravacitinib, and the price point of deucravacitinib ($75,000 a year) is higher than that of Otezla ($55,000 per year). It remains to be seen if these will be barriers to uptake.

$2.12B

expected sales in 2027

95%

probability of success for deucravacitinib
in the the European Union.

“BMS-986165 is an oral agent and seems well tolerated. The data that I see are very encouraging, so it looks as though they have efficacy that is as good as biologics. If that’s the case, then it’s very exciting.”