Novo Nordisk is hitting the gas on amycretin development. After posting phase 2 data, the company has decided to run pivotal diabetes trials of an asset that it previously saw primarily as an obesity prospect.
In September, Martin Holst Lange, M.D., Ph.D., chief scientific officer at Novo, told analysts the company felt it was “prudent” to investigate amycretin in diabetes but was mainly interested in studying the agonist of GLP-1 and amylin in obesity. Now, Novo has committed to starting phase 3 development of amycretin in Type 2 diabetes next year.
The Danish drugmaker decided to advance amycretin in diabetes after seeing phase 2 data in the patient population. Investigators enrolled 448 people with Type 2 diabetes that was inadequately controlled on metformin. About 40% of patients were using an SGLT2 inhibitor before starting the trial.
By Week 36, participants who received a weekly subcutaneous amycretin injection had dose-dependent reductions in the HbA1c blood sugar measure of up to 1.8%. HbA1c fell 0.2% in the placebo cohort. Mean HbA1c was 7.8% at baseline. HbA1c fell to below 7% in 89.1% of patients and to 6.5% or lower in 76.2% of patients.
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Another group of patients took amycretin as a once-daily oral formulation. By Week 36, HbA1c had fallen by up to 1.5% on the oral doses. HbA1c decreased 0.4% in the placebo cohort. Mean HbA1c was 8% at baseline. HbA1c fell to below 7% in 77.6% of patients and to 6.5% or lower in 62.6% of patients.
Novo also tracked the effect of the subcutaneous and oral formulations on body weight. Patients on the subcutaneous formulation had lost up to 14.5% of their body weight, from a mean baseline of 99.2 kg, by Week 36. Placebo patients lost 2.6% of their body weight. From a mean baseline of 101.1 kg, people on oral amycretin lost up to 10.1% of their body weight, compared to a 2.5% loss on placebo.
People on the highest subcutaneous amycretin dose were on the final maintenance dose for four weeks. Weight loss was yet to plateau at Week 36 on the higher subcutaneous and oral doses, Novo said. The finding suggests patients could lose more weight in longer trials, as has happened in studies of other GLP-1 drugs.
The safety and tolerability results showed the expected mix of mostly mild to moderate gastrointestinal adverse events, giving Novo a data set it believes supports further development of amycretin in Type 2 diabetes.
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Novo already has phase 3 data on CagriSema, a fixed-dose combination of a long-acting amylin analog and a GLP-1 receptor agonist. Lange said in September that Novo’s base case is that amycretin, a single molecule that hits the same receptors as the two-drug CagriSema, will have the same safety, tolerability and efficacy as its more advanced sibling.
If amycretin hits Novo’s base case, Lange said amycretin will be “a very valuable offering for us because it’s one molecule.” Amycretin can be delivered in a single-chamber device and could be easier to scale because Novo only needs to make one active ingredient, rather than the two for CagriSema.
Novo reported a 2.2% mean change in HbA1c and a 15.6% reduction in body weight in people who took CagriSema for 32 weeks in a small phase 2 trial. At Week 68 of a phase 3 CagriSema trial, body weight fell 13.7%, and 73.5% of patients had an HbA1c of 6.5% or less. The amycretin data are in the same ballpark as results from trials of CagriSema and rival drugs from companies including Eli Lilly.
Shares in Novo, which dropped yesterday on news of Alzheimer’s disease failures, climbed more than 4% to approach 300 Danish kroner ($46) after the company shared the amycretin data.