Innovative JAK inhibitor phase III clinical results achieved breakthrough results, significantly improved psoriasis symptoms and good safety

On April 24, 2021, Bristol-Myers Squibb (BMS) announced the positive results of its potential "first-in-class" oral selective TYK2 inhibitor deucravacitinib in the treatment of patients with moderate to severe psoriasis Phase III clinical trials
.

The test results showed that compared with placebo and common oral therapy, deucravacitinib significantly increased the proportion of patients whose skin symptoms were almost completely cleared, and the efficacy was maintained until week 52

Innovative JAK inhibitor--the safety advantage of Deucravacitinib

In recent years, while JAK inhibitors have achieved great success, their safety has also attracted wide attention.
For example, in 2019, the FDA proposed the safety of Pfizer’s tofacitib (Xeljanz XR), the world’s first approved JAK inhibitor.
Warning: The safety test found that the use of high-dose tofacitinib in patients with rheumatoid arthritis would cause the risk of pulmonary embolism and death, and a new black box warning was required in the box
.

As a result, the pharmaceutical industry began to focus on another member of the family-Tyk2

Tyk2 is a member of the JAK family and is an intracellular signal kinase that mediates the signal transduction of IL-23, IL-12 and type I interferon (IFN)
.

The JAK family includes four proteins: JAK1, JAK2, JAK3, and Tyk2.

Deucravacitinib developed by BMS is an oral selective TYK2 inhibitor
.

It combines with the regulatory domain of TYK2 to "lock" TYK2 in an inactive state, thereby selectively inhibiting the activity of TYK2

Deucravacitinib has a unique mechanism of action (picture source: Bristol-Myers Squibb official website)

In two randomized, double-blind, placebo and oral active-controlled Phase 3 clinical trials, a total of more than 1,600 patients with moderate to severe psoriasis received deucravacitinib, PDE4 inhibitor apremilast, or placebo
.

The patient’s skin symptoms are measured in an assessment method

Using PASI 75 (meaning a 75% improvement in the patient’s psoriasis area and severity index) as a measure, after 16 weeks of treatment, the proportion of patients treated with deucravacitinib that reached PASI 75 was 58.
7% and 53.
6%, respectively, which was significantly better In the active control group and placebo group
.

And this proportion has further increased with the continuous treatment, increasing to 69.

Deucravacitinib significantly improved the proportion of patients reaching PASI 75 (picture source: reference 2)

In terms of safety, deucravacitinib also has a good performance.
The proportion of patients who withdrew from the trial due to adverse reactions was lower than that of the placebo and active controls
.

Moreover, the blood samples of the patients did not find the characteristics of adverse reactions associated with the usual JAK inhibitors

In addition, deucravacitinib is also undergoing a large number of clinical trials for indications such as psoriatic arthritis, ulcerative colitis, Crohn's disease, lupus nephritis, and systemic lupus erythematosus
.

Research and development status of domestic JAK inhibitors

In the Chinese market, in addition to importing innovative JAK inhibitors and domestic generic drugs of tofacitib, there are also many companies developing domestic innovative JAK inhibitors
.

The projects that have entered the clinical trial stage are shown in the following table.

(According to public information incompletely sorted out)

As for JAK inhibitors, 8 drugs have been approved for the market worldwide, and dozens of drugs are still in the clinical stage, and the competition is fierce
.
For future JAK inhibitors to achieve commercial success, they must make appropriate improvements and take the road of differentiated R&D
.
The side effects of existing JAK inhibitors are still relatively large (black box warning), which will inevitably have an impact on the expansion of the market
.
Whether deucravacitinib's innovative layout can stand out in the fierce competition in the future, we will wait and see
.

       Reference source:

       1.
Bristol Myers Squibb Presents Positive Data from Two Pivotal Phase 3 Psoriasis Studies Demonstrating Superiority of Deucravacitinib Compared to Placebo and Otezla® (apremilast).
Retrieved April 23, 2021, from https://investors.
bms.
com/iframes/press- releases/press-release-details/2021/Bristol-Myers-Squibb-Presents-Positive-Data-from-Two-Pivotal-Phase-3-Psoriasis-Studies-Demonstrating-Superiority-of-Deucravacitinib-Compared-to-Placebo- and-Otezla-apremilast/default.
aspx;

       2.
AAD 2021 Investor Presentation.
Retrieved April 23, 2021, from https://s21.
q4cdn.
com/104148044/files/doc_presentations/2021/AAD-Investor-Presentation.
pdf;

       3.
BMS official website.