Amycretin

Kallyope has removed one of its weight loss candidates from its online pipeline and shuffled metabolic diseases lower on its priority list, below its efforts on neurological disorders.The changes on the company's website were spotted this week after the results of a Phase II obesity study were quietly posted to ClinicalTrials.gov — the same day a Phase IIb trial testing Kallyope's elismetrep (K-304) in patients with migraine was listed on the site.The obesity study's outcome could, in part, explain the lack of fanfare. While the combination of Kallyope's two oral "nutrient receptor agonists" K-757 and K-833 may have demonstrated a more tolerable gastrointestinal (GI) profile than other oral contenders, the rate of weight loss seen in the study falls well short of the levels achieved by the pack leaders (see – Vital Signs: A safety snapshot of oral GLP-1s).Kallyope had raised a $236-million series D in 2022 on the strength of its metabolic and GI programmes.Less than 3% weight lossKallyope was evaluating K-757 alone, and in combination with K-833, against placebo in 155 participants with obesity and without diabetes. The company has previously described the two compounds as agonists that "stimulate the secretion of multiple appetite-suppressing satiety hormones, including GLP-1, and several other well validated satiety hormones, such as PYY and CCK" (see – Vital Signs: Mapping the next generation of obesity targets after GLP).After 13 weeks, K-757 led to a 1.57% reduction in weight from baseline, while patients who received the duo saw a 2.94% decline; those in the placebo arm had a 0.15% reduction.Of the 52 patients who received K-757 plus K-833, 14 discontinued treatment due to an adverse event (AE). The overall AE rate in the cohort was 80.8%, with the most common side effects being nausea (51.9%), constipation (36.5%), vomiting (23.1%), dyspepsia (19.2%) and diarrhoea (11.5%).K-833 is no longer listed on Kallyope's pipeline, leaving K-757 as the sole disclosed metabolic candidate. The company lists three undisclosed assets in the discovery stage for the disease area, while three neurology programmes are named on its website. Outshined by competitors Keeping in mind the caveats with cross-trial comparisons, the rate of weight loss seen with Kallyope's combo appears to be less than a quarter than that of Novo Nordisk's oral obesity hopeful in a similar timeframe. At the European Association for the Study of Diabetes (EASD) meeting last year, the Danish drugmaker reported that patients given oral amycretin achieved mean weight loss of 13.1% after 12 weeks.Two other oral candidates have achieved a greater degree of weight loss in less time — albeit in far fewer participants. Roche's CT-996 showed placebo-adjusted mean weight loss of 6.1% in six patients at week four in a Phase I study; and earlier this month, China-based Ascletis reported up to a 6.2% weight reduction at week four in eight patients given its homegrown oral GLP-1 agonist ASC30. Phase III data for Eli Lilly's oral GLP-1, orforglipron, are due next quarter — and it's one of the most highly anticipated readouts of the year. At the American Diabetes Association (ADA) scientific sessions in 2023, the pharma reported weight loss of up to 12.6% after 26 weeks (see – Spotlight On: Viking, Structure prep for Eli Lilly's oral GLP-1 reckoning).

The FDA on Tuesday broadened the label of Novo Nordisk’s blockbuster diabetes drug Ozempic. The GLP-1 injectable can now also be marketed for the reduction in risk of worsening kidney disease, kidney failure (or end-stage kidney disease) and death due to cardiovascular disease, according to a Tuesday press release. The label applies to adults with type 2 diabetes and chronic kidney disease. The Danish pharma giant said the boosted label makes Ozempic the most broadly indicated GLP-1 agonist in its class. Novo and Lilly are in a duopoly for the GLP-1 class, and each of the pharma giants has poured billions of dollars into manufacturing acquisitions, site updates and new factory builds. The move comes as Novo looks to build out its diabetes and obesity franchise. Results from a next-generation approach, called CagriSema, underwhelmed investors last month and tanked the company’s shares. The company also presented data on an amycretin candidate earlier this month. The FDA made the decision based off the Phase 3 FLOW trial, which read out last year . “A large portion of patients I treat experience serious kidney complications and comorbidities, with some even requiring dialysis,” Richard Pratley, a FLOW trial co-chair and medical director at the AdventHealth Diabetes Institute, said in a press release. “Today’s decision by the FDA offers hope for the millions of adults living with both conditions and provides an additional treatment option, representing a significant advancement for my patients.” Ozempic was first approved in 2017. Earlier this month, it was added to the US government’s second round of Medicare price negotiations under the Inflation Reduction Act. Compounding pharmacies continue to deliver semaglutide, the active ingredient in Ozempic and the obesity drug Wegovy. Telehealth provider Hims & Hers is showcasing its role in the contentious rollout of compounded drugs in a Super Bowl ad .