Phase 3 trials of Kailera Therapeutics’ oral GLP-1 prospect have hit their primary endpoints, positioning the biotech’s partner Hengrui Pharma to seek approval in obesity and diabetes in China.
Hengrui is developing the once-daily oral small molecule GLP-1 receptor agonist HRS-7535, which Kailera calls KAI-7535, in Greater China. The Chinese biotech shared data on Tuesday from two phase 3 trials, one in adults with obesity or overweight, and one in adults with Type 2 diabetes. Kailera, which has rights to the asset outside Greater China, began a phase 2 trial in people with obesity or overweight in April.
Hengrui’s obesity study linked HRS-7535 to mean weight loss of up to 10.9% at Week 44, compared to 2.5% for placebo. Weight loss climbed to 11.1% at Week 50 in an ad hoc analysis. The analyses excluded data collected after premature treatment discontinuations or the use of drugs with an obvious effect on weight. Including those data, weight loss on the high dose of HRS-7535 slipped to 9.8% at Week 44.
The weight loss results are in the same ballpark as data on existing oral GLP-1 drugs, namely Eli Lilly’s Foundayo and Novo Nordisk’s Wegovy pill. Lilly linked (PDF) Foundayo to weight loss of up to 11.1% at Week 72. Novo reported (PDF) 13.6% weight loss at Week 64.
At a Jefferies event last month, Kailera CEO Ronald Renaud predicted that most oral drugs “are going to have weight loss in a very tight band, somewhere between 10% and 15%.” With multiple drugs offering similar weight loss, safety and tolerability is “where the differentiation happens,” Renaud said.
Seventy per cent of patients taking HRS-7535 in the obesity trial had nausea, making it the most common treatment-emergent adverse event. The nausea rate on placebo was 16.2%. Meanwhile, vomiting affected up to 68.6% of people on HRS-7535, compared to 4.5% of participants on placebo. The diarrhea figures for HRS-7535 and placebo were 36.9% and 15.3%, respectively.
For comparison, Nausea, constipation, diarrhea and vomiting, the four most common adverse events in Lilly’s phase 3 program, affected 24% to 35% of participants. Novo reported nausea and vomiting rates of 46.6% and 30.9%, respectively, in a phase 3 trial of oral Wegovy.
Hengrui reported the obesity data alongside results from a phase 3 trial of HRS-7535 in people with Type 2 diabetes. Excluding data collected after premature treatment discontinuations or the use of other glucose-lowering medications, HRS-7535 achieved reductions in HbA1c—a measure of blood sugar—of up to 1.68%. HbA1c fell by 1.28% on dapagliflozin, an SGLT2 inhibitor that AstraZeneca sells as Farxiga.
The readouts expand the evidence on one of two oral weight-loss drugs in development at Kailera. The biotech is also advancing an oral peptide that targets GLP-1 and GIP. Kailera, which raised an impressive $625 million in an IPO in April, could report topline phase 2 data on the oral candidates next year.