Three months ago, Japanese pharmaceutical giant Takeda paid a biotechnology startup $4 billion for an experimental drug in one of the largest deals of its kind in industry history. On Saturday, Takeda revealed clinical trial results that show why it was willing to write such a large check.
The data, being presented at the American Academy of Dermatology meeting, are from a study of the drug in people with moderate-to-severe plaque psoriasis, a chronic condition that causes itchy and scaly skin patches. They’ve been eagerly anticipated since November, when the medicine’s original developer, biotechnology company Nimbus Therapeutics, said the drug could be the best of its type — suggesting potential to top a similar medicine from Bristol Myers Squibb that’s already on the market.
The results disclosed Saturday don’t yet prove that claim. The study was a relatively small mid-stage test, evaluating participants for just three months. Bristol Myers’ medicine, sold as Sotyktu, has also set a high bar for would-be competitors to clear.
Nonetheless, the data appear to show Takeda’s drug, TAK-279, as competitive with Sotyktu, and potentially superior to it if similar results are obtained in larger and longer trials. Accorrding to Andy Plump, Takeda’s president of R&D, the highest tested doses of TAK-279 led to a degree of skin clearance that hasn’t been previously shown with an oral pill and approaches that of more potent injectable drugs.
Side effects, including acne and viral infections, were mostly mild to moderate, Plump added in an interview. There weren't any serious cases of low white blood cell counts, which was flagged as a concern by analysts following earlier results. (Takeda shared with BioPharma Dive a press release that included summarized data ahead of Saturday’s presentation, but didn’t detail findings further.)
“The data are outstanding,” he said. “This is why we ended up doing the deal.”
TAK-279 is one of many medicines in development that target TYK2, an enzyme involved in cell signaling pathways that are implicated in inflammation. These treatments have become highly coveted by drugmakers because of their potential to be oral alternatives to top-selling, injectable medicines like Humira.
Last September, the Food and Drug Administration made Sotyku the first TYK2 inhibitor approved, clearing it for psoriasis. Notably, the agency didn’t require warnings for potentially serious safety risks associated with another similar group of oral autoimmune disease drugs. The regulator also didn’t mandate that patients first try biologic drugs, boosting the market opportunity for TYK2 blockers.
Nimbus, a well-funded, Cambridge, Massachusetts-based biotech, quickly capitalized. The company had been developing its own TYK2 inhibitor for a decade, and long argued its molecule was more selective, meaning higher doses could be safely used.
Two months after Sotyktu’s approval, Nimbus declared success in its Phase 2 trial and shared the findings confidentially with a wide group of drugmakers. A bidding war ensued that Takeda won, Plump and Nimbus CEO Jeb Keiper told BioPharma Dive. The data shared Saturday for the first time reveal in detail what those companies were bidding on.
Nimbus’ study enrolled 259 patients, who received either a placebo or one of four different doses of its drug every day for three months. The study compared the proportion of participants given either placebo or Nimbus’ drug that achieved at least a 75% reduction on a measure known as PASI that assesses the severity and size of skin lesions.
Roughly two-thirds of volunteers given the highest two doses tested — 15 mg and 30 mg per day — met that goal, as did 44% of those given the next lowest dose of 5 mg. By comparison, only 6% of participants on placebo experienced a 75% or higher PASI improvement. (A fourth lower dose didn’t meet the threshold for statistical improvement over placebo.)
The drug also met the study’s secondary goal, with the three highest doses meaningfully reducing patients’ scores on a doctors’ assessment of severity called PGA. According to Takeda, the 5 mg, 15 mg and 30 mg doses led to PGA scores of zero in 10%, 15% and 33% of patients, respectively. A PGA score of zero indicates fully clear skin. No one on placebo met that mark.
Takeda said between 53% to 62% of patients on the drug experienced adverse events that included COVID-19, acne, a type of skin rash and diarrhea, versus 44% of placebo recipients. One patient who received the 15 mg dose experienced a buildup of fluid in tissues surrounding the lungs and heart, which was classified as two serious adverse events but judged by trial investigators to be unrelated to treatment.
Though comparing drugs across studies is difficult, analysts and investors are likely to stack Takeda’s medicine up against Sotyktu. The approval of Bristol Myers’ drug was based on a pair of trials that showed more than half of patients achieved a three-quarter PASI reduction after four months, a result that appeared to get better with time. In addition, the rates of 75% reductions in PASI scores after three months in Bristol Myers’ Phase 2 trial in psoriasis are comparable to what Takeda is reporting.
“It’s incumbent on everybody else to show superiority,” Bristol Myers’ Chief Medical Officer Samit Hirawat said in an interview in January.
Plump believes Takeda can, pointing to the rates of near-full or full skin clearance in its trial. Close to half of the patients who received one of the top two doses of TAK-279 had a 90% reduction in their lesions’ spread and severity. One third experienced a 100% reduction. Those numbers surpass what Sotyktu achieved in clinical testing and, to Plump, are proof of Nimbus’ drug’s selectivity.
The overall data also meet analyst projections. Analysts at the investment bank Stifel in a March 3 client note called a 40% difference in PASI 75 scores over placebo the “minimum bar” for Takeda, while a “convincing” result would be in the 60% to 70% range.
Takeda is betting heavily on the drug’s future as a result. The company is planning Phase 3 studies in psoriasis and psoriatic arthritis next year as well as a head-to-head trial against Sotyktu. It’s also considering mid-stage studies in lupus, Crohn’s disease and ulcerative colitis, and a team is looking into other diseases to target too, according to Plump.
“We’re looking at creative ways to understand activity in those additional indications and move rapidly,” he said.