Takeda has revealed the data that persuaded it to pay $4 billion for Nimbus Therapeutics’ TYK2 inhibitor. The highest dose completely cleared psoriasis in one-third of patients, adding weight to claims that the candidate is an improvement on Bristol Myers Squibb’s rival drug Sotyktu.
Late last year, Nimbus revealed that its TYK2 inhibitor, now known as TAK-279, hit the primary endpoint in a phase 2b clinical trial of moderate to severe plaque psoriasis patients. The biotech said the data “support best-in-class potential” but opted against sharing data to back up the claim. Weeks later, Takeda provided external validation of the claim by paying $4 billion upfront for the phase 3-ready candidate.
Now, Takeda has shared data from the 12-week clinical trial. At a late-breaking session at the American Academy of Dermatology Annual Meeting, the Japanese drugmaker revealed that 68% and 67% of patients at the middle and high dose level had a 75% resolution of their symptoms, as measured by the Psoriasis Area and Severity Index (PASI). The PASI 75 rate in the placebo group was 6%.
The difference in PASI 75 was enough for the study to hit its primary endpoint and suggest that the drug candidate may have an edge over BMS’ Sotyktu, which triggered 75% or greater improvements in psoriasis area and severity in 53% and 58% of patients in a pair of 16-week phase 3 clinical trials.
A clearer picture of the potential advantages of TAK-279 over Sotyktu emerges in the analysis of PASI 90 and PASI 100, which assess the proportion of patients with 90% and 100% resolution of symptoms. In the high-dose TAK-279 cohort, 46% of patients had PASI 90 and 33% had full resolution.
“The portion of patients achieving PASI 90 and PASI 100 already at Week 12 is particularly encouraging,” Graham Heap, Ph.D., Takeda’s global program leader of R&D, said on an investor call to discuss the data. “We know that achieving clear or nearly clear skin, PASI 90 and importantly PASI 100, is increasingly recognized as a therapeutic goal in psoriasis.”
The PASI 90 rates in the Sotyktu trials were 27% and 36%. The PASI 100 rates were 10% and 14%. TAK-279 achieved higher rates of PASI 90 and PASI 100 in less time than Sotyktu, although the relatively small size of the Takeda study and the unreliability of cross-trial comparisons mean it is unclear at this stage whether the investigational candidate is definitely more effective.
Heap noted the uncertainty, saying that “it’s difficult for us to do cross-trial comparisons with any other agents,” but still made the case that TAK-279 may have an advantage. “If we look at the rates that are currently seen in the Sotyktu label, we believe this offers a compelling proposition,” Heap said.
The next step is to show the efficacy holds up in phase 3. Heap said Takeda will continue talking with regulators over the coming weeks and months and share information on the design of the studies as it finishes the discussions. Heap said a “head-to-head trial in psoriasis has become relatively common.”
The discussions will determine the phase 3 dose, but the PASI 100 rate seen in the high, 30-mg cohort has made it a strong contender. Takeda thinks it is highly unlikely that it will need to start patients on a lower dose. Plans are afoot to study the candidate in other immune-mediated diseases such as systemic lupus erythematosus and inflammatory bowel disease.