Zalfermin

The day before Maziar Mike Doustdar officially begins his reign as CEO at Novo Nordisk, the company revealed alongside its second-quarter financial results a number of setbacks to its pipeline. These include two efforts in obesity, and one each in metabolic dysfunction-associated steatohepatitis (MASH) and dyslipidaemia.Having axed an experimental once-monthly dual GLP-1/GIP receptor agonist last year, Novo has now pulled the plug on efforts to develop a once-weekly therapy targeting the two receptors. The company said Wednesday that it completed a Phase II study of the GIP/GLP-1 co-agonist analogue, dubbed NNC0519-0130, in people with overweight or obesity in June. Although the primary endpoint of the trial was achieved, with NNC0519-0130 demonstrating statistically significantly greater body weight reductions compared with placebo after 36 weeks of treatment, Novo noted that it will not pursue further development "due to portfolio considerations."The company also disclosed the termination of work on INV-347, citing both portfolio considerations and the "pharmacokinetic profile" of the next-generation oral small molecule CB1 receptor blocker. The therapy was gained via the acquisition of Inversago Pharma in 2023, a purchase that earlier this year delivered a Phase II failure for the CB1 inverse agonist monlunabant (INV-202) in diabetic kidney disease.According to Novo, a Phase I study of once-daily INV-347 in participants with normal weight or overweight/obesity was completed in May. The company noted that while monlunabant had been associated with some mild-to-moderate neuropsychiatric side effects, INV-347 appeared to have a safe and well tolerated profile in the trial.Outside of obesity, Novo said that it terminated development of the long-acting FGF-21 analogue zalfermin (NNC0194-0499) in MASH due to portfolio considerations. A Phase II study in patients with MASH F2-F4, exploring a fixed-dose combination of zalfermin and semaglutide, was completed earlier this year.The drugmaker said that the trial failed to meet its primary endpoint of superior improvement in liver fibrosis and no worsening of MASH, compared to placebo.Meanwhile, work on ANGPTL3i in dyslipidaemia has been halted, again due to portfolio considerations. A Phase I study was completed in May, in which the monoclonal antibody appeared to have a safe and well-tolerated profile, but Novo has still ended work on the programme.

iStock, tadamichi Maziar Mike Doustdar, who was named as Novo Nordisk’s new CEO last week, spoke on a second quarter earnings call of reallocating resources to the company’s “main core” of metabolic disease. As the new CEO of Novo Nordisk, Maziar Mike Doustdar plans to lean into what the company knows best—obesity and diabetes—as he tries to steer the Danish pharma back into the leadership position in the incretin market. “We’re going to focus more on diabetes and obesity as this is our main core and has always been,” said Doustdar, who was named as the new chief executive last week more than a month after the departure of Lars Fruergaard Jørgensen was announced. Doustdar previously served as Novo’s executive vice president of internal operations; he starts his tenure as CEO on Thursday. “I think I’ve been put into this position because I execute good and I out compete my competition,” he told investors during the pharma’s second quarter earnings call on Wednesday, adding that he plans to continue this aggressive attitude in his new role as leader and infuse it across the rest of the company. “Execution, execution, execution,” he said. To power his drive for execution, Doustdar is also looking to move Novo’s resources around and funnel them into areas that matter the most. “We need to reallocate and look at our cost base and really put the money where the growth is,” he told investors, noting that such financial adjustments are important to “not fall behind the competition.” It was not clear on the call what specific reallocation strategies he plans to implement. In a Q2 earnings news release on Wednesday, Novo revealed the discontinuation of a handful of investigational assets, the most notable of which is zalfermin, a long-acting FGF21 analog that was being developed for metabolic dysfunction-associated steatohepatitis (MASH). “We did not see, from an efficacy perspective, a dramatic improvement, neither in monotherapy nor in combination [with semaglutide] above and beyond what we already know semaglutide can do,” Martin Holst Lange, executive vice president of development at Novo, said on the call. “We do not progress assets that are not differentiated in a meaningful way.” Novo also axed an antisense oligonucleotide that had failed a mid-stage study in acute myocardial infarction and the oral CB1 receptor blocker INV-347, which was in Phase I development for obesity. The pharma will also no longer work on ANGPTL3i, a monoclonal antibody for dyslipidemia. Novo’s Q2 performance was largely in line with analyst expectations. Revenues jumped 18% year-on-year to hit 76.9 billion Danish krone ($11.95 billion). The blockbuster GLP-1 injection Ozempic, indicated for type 2 diabetes, was the pharma’s best-selling asset at 31.8 billion Danish krone ($4.94 billion), representing 15% growth from the same period last year, and falling behind the consensus estimate by 1%. Wegovy, which uses the same active ingredient as Ozempic but is approved for chronic weight management, beat forecasts by 1% to earn 19.5 billion Danish krone ($3 billion) in the second quarter, a 67% year-on-year increase. Alongside the announcement of Doustdar’s appointment last week, Novo also lowered its full-year 2025 outlook. The company now expects sales growth to be from 8% to 14% at constant exchange rates, down from the previous forecast of 13% to 21%. Operating profit is now expected to grow from 10% to 16%, below prior guidance of 16% to 24%. “We don’t [take] our guidance reduction lightly,” outgoing CEO Jørgensen told investors on the call. “We treat it with utmost seriousness.” He added that he believes Doustdar will provide the “execution power needed” to deliver on the company’s aspirations for growth in the coming years. Jørgensen’s last day at Novo is Wednesday.