Weight-loss treatments have quickly emerged as one of the hottest areas for R&D in the pharmaceutical industry. The rapidly realized blockbuster sales of the leading drugs in the space, Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound, means there is a strong interest in the pipeline of follow-on and next-generation drugs.
J.P. Morgan forecasts that the glucagon-like peptide-1 (GLP-1) market alone will exceed $100 billion in revenue by 2030, through the use of these medicines in diabetes and obesity. According to IQVIA, the number of clinical trials for obesity drugs in 2023 was up by 68% from 2022, with 124 drugs in active development—of these, 40% are agonists of either the GLP-1 or glucose-dependent insulinotropic peptide (GIP) receptor.
“The focus continues to be mainly GLP-1-based therapies,” Graig Suvannavejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, told BioSpace, adding that there is a significant interest in combination approaches, such as Eli Lilly’s ‘triple-G’ approach, which binds and activates the GIP, GLP-1 and glucagon receptors.
Suvannavejh said the oral delivery of these medicines is also of significant interest, as it could lower the cost of current peptide treatments by enabling lower manufacturing costs. This would allow for a greater number of patients to receive these types of treatments, he said.
Of the assets that are moving through the pipeline, BioSpace highlights four potentially market-changing treatments. Though the focus of the industry’s pipeline has been on injectable GIP/GLP-1 assets, the leading companies have recognized the need to also approach the development of medicines from a new angle.
Novo Nordisk’s Cagrilintide and Semaglutide
Novo Nordisk is exploring a once-weekly subcutaneous combination of semaglutide and a novel amylin analog, cagrilintide. The use of an amylin analog would differentiate the company’s treatment portfolio from the current pipeline dominated by GIP/GLP-1 assets. Novo has already set the combination treatment, known as CagriSema, head-to-head against Eli Lilly’s Zepbound in a Phase III trial. In Phase II, the combination demonstrated greater body weight reduction in overweight people with type II diabetes. Body weight reduction was 15.6% with CagriSema compared to 5.1% in the semaglutide-only group and 8.1% in the cagrilintide-only group.
Eli Lilly’s Orforglipron
Eli Lilly has various assets in Phase III trials for weight loss, including orforglipron, which is a GLP-1 receptor agonist that is delivered as a once-daily oral treatment. Leaders in this space are racing to be the first-to-market with an oral treatment. This could be significant in garnering market share due to the aforementioned manufacturing advantages and the fact that oral delivery is generally preferable to subcutaneous delivery. In Phase II trials, orforglipron achieved statistically significant dose-dependent body weight reductions for all doses tested, according to Lilly’s June 2023 announcement.
Viking Therapeutics’ VK-2735
In February, Viking Therapeutics revealed positive clinical trial results for its obesity candidate, VK2735—a dual GLP-1/GIP agonist, similar to Lilly’s Zepbound. Phase II results showed that the drug was able to achieve up to 13.1% placebo-adjusted mean weight loss. Then, last month, Phase I results revealed that an oral formulation of the treatment led to reductions in mean body weight. There were very few gastrointestinal adverse events reported 28 days after receiving VK2735, which could be an important differentiator as these side effects are a chief complaint associated with GLP-1 medicines.
“Viking is viewed as one of the companies at the forefront of working on an oral formulation,” Suvannavejh said. The company noted in its Phase I data announcement that it would explore “longer treatment windows and potentially higher doses” in Phase II. Suvannavejh said this is because tolerability of the treatment appeared to be “quite good.”
Outside of Lilly and Novo Nordisk’s portfolios, VK2735 is one of the furthest along in clinical development, so these data could signal the approach of a third player on the market—whether that be Viking or a future suitor of the company, with Suvannavejh suggesting that the company could be an acquisition target in the future.
Inversago Pharma’s INV-202
A lesser-known drug candidate but backed by Novo Nordisk’s financial firepower, the CB1 receptor blocker could be another angle of attack for weight loss therapies. In June 2023, two months before Novo Nordisk’s $1 billion buyout, Inversago posted Phase Ib results for INV-202, an oral treatment, which elicited an average weight loss of 7.7 pounds for those treated with the candidate over a 28-day period, compared to 1.2 pounds for placebo comparators. The treatment has been specifically designed to block CB1 receptors in peripheral tissues to avoid the adverse events previously associated with the targeting of this pathway.
Suvannavejh said these four treatments could be positioned as “combination approaches, and in patients who do not respond to GLP-1 or cannot tolerate the side effects.”
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