Lilly takes on Novo in obesity

The data from the first and largest of Lilly’s pivotal trials of tirzepatide in obesity are in, and the GIP/GLP-1 agonist has smashed the target set by Novo’s Wegovy. Patients given the highest dose in the Surmount-1 study lost more than 20% of their body weight, a result that beat many expectations.

Importantly, tolerability also looks competitive to Wegovy and in line with hopes, with Lilly also highlighting low discontinuation rates. Describing the data as “at the top end of what we thought possible”, the company’s chief medical officer Dan Skovronsky said talks will now be sought with regulators about filing on this first trial alone. 

Previously, Lilly had agreed with the FDA that a filing would be made once the Surmount programme had completed reading out; the three remaining trials are due to yield data in mid-2023. Should the agency agree to review the drug sooner, Lilly’s attempts to grab share of the burgeoning obesity market from Novo would be given a major boost.

Mr Skovronsky declined to say whether a recently acquired priority review voucher would be used to speed any submission, but given Lilly's huge investment in this asset, tirzepatide would be presumably be a prime candidate for such a move.

“To be clear, we are not announcing an early filing – we are just discussing the next steps” with regulators, Mr Skovronsky told analysts on Lilly’s first-quarter earnings call today. “But given the huge market need, we think it warrants trying to find a path to accelerate [tirzepatide] to market.”

The data and the potential for a quicker launch was enough to send Lilly shares up 2% in early trade; Novo Nordisk sank 2.5%.

Mike Mason, head of diabetes for Lilly, cautioned that should tirzepatide reach the market “it won’t sprint out of the gate”. While there is considerable long-term potential, demand is likely to build slowly, he said.

Poor reimbursement has long been an issue for obesity drugs, although Mr Mason said that is improving, thanks to the significantly better data being generated with tirzepatide and Wegovy versus results seen with older options.

“Former agents were more cosmetic than offering real health benefits. The [reimbursement] trends are moving towards better access,” he said, adding that if Lilly can show tirzepatide can help improve related conditions like sleep apnoea, the gates could open even more easily.  

The results 

As for the data, Novo Nordisk will be shifting nervously today. Even patients on tirzepatide's lowest dose lost a similar amount of weight as patients in a similar study of Wegovy – the caveats of cross-trial comparisons notwithstanding – as the graph above shows. And tirzepatide had a much cleaner tolerability profile than Novo’s drug.

At the other end of the dose range, the 15mg high dose of tirzepatide prompted notably better weight loss than Wegovy, and tolerability remained better. It should be noted that these endpoints were assessed at slightly different time points – 72 weeks for tirzepatide and 68 weeks for Wegovy.

As well as the headline weight loss figures, tirzepatide also hit an important secondary endpoint, with 30%, 50% and 57% of patients taking the 5, 10 and 15mg doses respectively losing at least 20% of their body weight, versus 3% on placebo. Wegovy’s trials did not assess this metric, instead looking at those who lost more than 15% of their weight. 48% of these patients hit that target, compared with 4.8% in the placebo group. Tirzepatide thus appears to have cleared a higher bar.

The two molecules do not act in precisely the same way: Wegovy is a GLP-1 analogue whereas tirzepatide is a GIP/GLP-1 agonist. Both are prone to gastrointestinal side-effects. Here too Lilly’s agent seems to come out ahead.

For now, Wegovy is forecast to be the biggest seller for obesity in 2026, with Evaluate Pharma’s consensus data placing that year’s sales at $3.9bn. With this success and Lilly clearly gunning for a faster path to market, Novo will need to work hard to keep its early gains.