There is one overarching question for the developers of obesity drugs who aren’t Novo Nordisk or Eli Lilly: how on earth to take on these incumbents, who are so far entrenched in the space that they are essentially uncatchable?
Several executives from companies attempting to carve out a share spoke on this issue and others at FT Live’s Global Pharma & Biotech Summit, held in London on 5-7 November, and one message was that differentiation would be key.
“We will be coming a number of years later to present another drug that treats obesity,” said Waheed Jamal, head of cardiovascular, renal and metabolism at Boehringer Ingelheim, during a panel discussion on November 7. “The important thing is to go beyond just the pure weight loss and show that based on the mechanism of action that you have, and the disease biology that you’re dealing with in certain subtypes of the disease, the phenotype, that you can specifically improve patient outcomes.”
Boehringer is co-developing survodutide, a GLP-1/glucagon agonist, with Zealand Pharma. The drug’s pivotal trials, SYNCHRONIZE-1 in non-diabetic patients with obesity, and SYNCHRONIZE-2 in patients with both diabetes and obesity, will report towards the end of next year. By the time survodutide might gain approval, Novo’s Wegovy (semaglutide) will have been on the market for around five years.
Jamal said that demand for incretins is unlikely to slacken in that time. “GLP-1 agonists aren’t perfect [but] I do believe they’ll be the backbone for a long time to come,” he said. “The important thing is to generate outcomes.” Survodutide is also being studied in metabolic-associated steatohepatitis (MASH), but more germanely is in a 5,000-patient cardiovascular outcomes trial – the kind of trial most obesity therapies are going to have to prove their worth in if they are to make any kind of commercial splash.
“If you’re differentiated enough and you can show that benefit either directly due to weight loss or indirectly due to the other pleiotropic effects, then I think you have a reason to exist,” Jamal said.
Differentiation
Speaking two days earlier, Robert Bradway, CEO of Amgen, also stated that having an edge over existing medicines is important. Amgen’s lead obesity candidate is MariTide (maridebart cafraglutide), an antibody-drug conjugate which is approaching a make-or-break Phase II readout. MariTide has two possible points of differentiation: its mechanism and its potentially less frequent dosing schedule.
“We are approaching this differently from our peers. We’re approaching this with a GLP-1 agonist … but we’re also then antagonizing what’s called the GIP receptor. And we’ve chosen to antagonize that receptor based on human genetic data that demonstrates that people who have a knockout of that receptor normally are resistant to putting on weight,” he said.
Bradway also made the point that the battleground is extending beyond obesity per se: “We expect to be able to significantly reduce weight in the people who use this therapy. Now, what has emerged … is that there are benefits across a number of other diseases or organ systems that go along with that therapy.
“We’re very excited about the potential for addressing heart failure patients and addressing atherosclerotic disease and other problems in cardiovascular medicine. We’re very excited about what this therapy might represent for kidney disease patients.” he said. “We see not just an opportunity to treat the weight, but also the downstream consequences of that, and that’s where I think it begins to make a very big difference in society.”
Vibrant
This could be a useful point for prying payers’ purse-strings apart. Insurers and particularly governments have been leery of funding obesity meds simply because the huge patient population could all but bankrupt payment programs such as Medicare.
“If we can get at some of these root causes of chronic disease, we can begin to get at the costs to the healthcare system,” Bradway said. “Our healthcare systems are straining under the weight of an aging population. The beauty of medicines like those we’re involved in innovating is the potential to prevent or to delay serious illness, to keep people out of the hospitals, which are the most costly part of the healthcare system.”
Clive Meanwell, managing partner at the investment firm Population Health Partners, believes that focusing on the benefits to the economy that would come with widespread treatment of obesity could be a way of persuading payers to reimburse these therapies.
“Currently, less than 5% of the people who could benefit medically are being treated, and so there’s enormous growth for these indicated reasons where reimbursement, where governments and health systems are going to play – eventually, at the right price, with the right data,” he said.
Amgen’s Bradway also sees the reimbursement climate eventually shifting. “We as an industry will need to help educate the government as to why it makes sense to reimburse these medicines, why that’s a wise investment.”
He added: “I think the data will be strong for making that case, so I would expect the position here to evolve over time. To the extent that there is a market for these medicines, and the extent that the market enables the price to be set for those medicines, I think that there will continue to be a vibrant demand and a vibrant supply of medicines for obesity.”
Ultimately persuading payers to reimburse comes down to the same thing as paying regulators to approve: clinical data, in obesity and beyond. The next couple of years will decide exactly how big the market for metabolic therapies will become and who, aside from Novo and Lilly, will benefit from it.
