With Positive Phase II Data, Nimbus' Psoriasis Therapeutic Poised to Challenge BMS

 Nimbus Therapeutics reported positive Phase IIb results on Wednesday for its TYK2 inhibitor, NDI-034858, in moderate-to-severe plaque psoriasis.

Researchers hope the candidate will have the efficacy of JAK inhibitors without the safety issues. 

The study of 259 patients for NDI-034858 hit the primary efficacy endpoint. It demonstrated a statistically significant greater percentage of patients reaching a 75% improvement in skin lesions as measured by the Psoriasis Area and Severity Index (PASI-75) compared to placebo at 12 weeks.

The study also met other endpoints, and the safety was consistent with other drugs in its class.

In its announcement, the company did not detail the safety profile, which is a key issue in developing TYK2 inhibitors over existing JAK inhibitors. JAK inhibitors are effective in treating inflammation associated with autoimmune diseases, but adverse events have included dyslipidemia, and infections including herpes zoster reactivation, malignancies, anemia, leukopenia and cardiovascular issues.

The selective inhibition of TYK2 decreases the potential of adverse events seen with JAK inhibitors.

The therapy is also being evaluated in an ongoing Phase IIb trial in active psoriatic arthritis. The company plans to launch Phase III trials in psoriasis and future studies in other autoimmune diseases, such as inflammatory bowel disease and lupus.

JAK inhibitors on the market, such as Pfizer’s Xeljanz (tofacitinib), Eli Lilly’s Olumiant (baricitinib) and AbbVie’s Rinvoq (upadacitinib), are issued with black box warnings about the increased risk of blood clots and death. In a January post, the FDA wrote, "Recommendations for health care professionals will include consideration of the benefits and risks for the individual patient prior to initiating or continuing therapy.”

In September, the FDA approved Bristol Myers Squibb’s Sotyktu (deucravacitinib), a first-in-class, oral TYK2 inhibitor for moderate-to-severe plaque psoriasis. The company noted that it was the first oral treatment approved for the indication in almost 10 years and the first once-a-day oral treatment for moderate-to-severe plaque psoriasis.

Armstrong, who was also a clinical investigator in BMS’s POETYK PSO clinical trial, noted the drug had “the potential to become the new standard of care oral treatment for people with moderate-to-severe plaque psoriasis."

Nimbus likely hopes to position NDI-034858 as a competitor to BMS’s Sotyktu, even though it is significantly behind in getting to market.

The company has indicated it plans to release additional details at a future medical conference. 

https://www.biospace.com/article/nimbus-therapeutics-tyk2-inhibitor-shows-promise-in-phase-iib-for-plaque-psoriasis/