Weight loss gold rush: Developers vie for next blockbuster treatment

Weight loss treatments are rapidly becoming a focal point for pharma R&D, driven by the commercial success of Eli Lilly and Novo Nordisk’s therapies. With over 100 potential treatments in the pipeline and a surge in innovation, Ben Hargreaves finds the race is on to develop a next-generation solution for obesity.

The pipeline of potential treatments has grown to over 100 assets – late stage trials are particularly well-represented, with 36 phase 3-stage trials on-going. Morgan Stanley estimated that the global market for obesity drugs could be set to increase more than 15-fold, with an expectation that 9% of the US population could be taking such drugs by 2030.

For drug developers, the commercial potential of the area means that there is a gold rush of R&D occurring, where many companies are looking to be the first to bring a next-generation treatment to market. At the head of the pack are the current therapeutic area leaders, Lilly and Novo Nordisk, with the former having five obesity-focused assets moving through early to late-phase trials and the latter having seven product candidates. However, there is a surge of R&D and approaches, making the emergence of a serious contender to the two companies’ dominance inevitable.

New angles of attack

Like any treatment area, one new type of therapy can arrive and rapidly become the standard of care, rendering obsolete, or at least less profitable, the previous incumbents. For those conducting R&D into developing a new form of weight loss therapy, the most obvious target is the development of an oral treatment.

Lilly and Novo Nordisk’s GLP-1 agonist treatments are currently delivered weekly via injection. This form of delivery may be complicated by the high prevalence of needle phobia that exists within the general population, which has been noted as being as high as 35%. An oral treatment could therefore see increased uptake, with research having previously found a preference for oral treatments over injections. In addition, an oral treatment could address the capacity issues that have plagued the current market leaders, allowing for a potential reduction in the price of the treatment and therefore a broader coverage.

As such, there is a race by major obesity drug developers to successfully commercialise an oral treatment. Earlier this year, Novo Nordisk released that its potential oral therapy, NN9487, was able to outperform Wegovy (semaglutide) in phase 1 trials. The company also has a further oral candidate that has already progressed through phase 3 trials.

Lilly’s orforglipron is also currently in phase 3 trials, after posting phase 2 data showing that the potential treatment was able to achieve 14.7% mean weight reduction in overweight or obese adults. As an outlier, not being a big pharma company, Viking Therapeutics has developed a potential oral treatment, which has completed phase 2 studies and was able to reveal positive results, making it one of the leaders in the race to potentially develop a viable oral therapy.

The pipeline is not limited to innovations on the GLP-1 agonists, with various approaches moving through the clinic looking to improve the efficacy or safety of the current therapies. One is emerging from within Lilly’s pipeline, in the form of bimagrumab, which is a monoclonal antibody targeting ActRIIA/ActRIIB. One of the positive aspects of this treatment is the lack of weight rebound in clinical trials following a 12-week period after stopping treatment.

Beyond this, smaller companies are taking novel approaches to tackling weight loss. An example is a novel monoacylglycerol transferase 2 (MGAT2) inhibitor being developed by Shionogi, which is delivered in capsules. A clinical-stage biotech, NeuroBo Pharmaceuticals, is also taking a different approach by trialling a long-acting oxyntomodulin peptide analogue, DA-1726, that was able to show superior weight loss and similar hypoglycaemic effects when compared to Novo Nordisk’s Wegovy in trials.

Expanding pipeline

The burst of activity from smaller companies means that M&A in the space is beginning to heat up. The main two players, Lilly and Novo Nordisk, are behind many of the acquisitions, having the extra capital on hand from the revenue of their weight loss products to fund the deals.

Last month, Lilly paid up to $1 billion to form a partnership with Haya Therapeutics. The latter company is focused on identifying potential RNA therapies in the ‘dark genome’ to treat chronic conditions, in this case for obesity. The deal adds to a $494 million agreement with Fauna Bio to apply AI drug discovery for multiple targets in weight loss, which was concluded at the end of 2023.

Novo Nordisk has been just as active in making smaller-scale deals to expand its portfolio, such as through a research partnership with Metaphore, valued up to $600 million. The agreement will see the two companies look to develop two ‘next-generation’ therapeutics for obesity management. The big pharma company also agreed a $255 million licensing deal with EraCal to develop its oral small molecule programme in the area.

Big pharma, big interest

It is not just Lilly and Novo Nordisk building out pipelines in the area: other big pharma companies are now circling to try to break into the market. Pfizer is one of the main companies trying to play catch up, deciding in July to pursue a once-daily version of its oral, modified-release GLP-1 agonist, after a twice-daily version had resulted in a high rate of drop-out from trials.

Roche joined the group in pursuit of a section of the market through its $3.1 billion takeover of Carmot Therapeutics. The deal gave the company access to an oral obesity drug candidate and it posted phase 1 data from the once-daily pill, known as CT-966, in July. The treatment candidate resulted in an average weight loss of 7.3% at four weeks and Roche announced that it planned to progress the potential therapy into phase 2 trials.

Rather than pursue an acquisition, Boehringer Ingelheim is working with Zealand Pharma to develop survodutide, which is an injectable treatment that is combined with glucagon. The candidate has already progressed into phase 3 trials, with earlier trials showing that it could help patients with 19% weight loss.

With a wave of treatments showing potential in weight loss, the next step for the next-generation of treatments may not just be convenience, but also helping with other co-morbidities and health risks. Novo Nordisk received approval from the FDA in March, which provides Wegovy with an expanded indication to reduce the risk of cardiovascular death, both heart and stroke. In August, Lilly was able to show that treatment with Mounjaro (tirzepatide) has the potential to reduce the risk of worsening disease in people with heart failure and obesity.

With such a large potential market for obesity patients and broader health benefits from the treatments’ use, the industry is likely to see its pipeline of potential therapies continue to expand rapidly. The big question will be which candidates in development will become the leaders of the next-generation of therapies.