Novo Nordisk’s Ozempic is already ducking it out with Eli Lilly’s Trulicity in the once-weekly diabetes treatment field. But looming competition from the Indianapolis pharma could pose a serious threat, especially at its lowest tested dose, one analyst said.
That’s the tentative conclusion Bernstein analyst Ronny Gal reached after delving into results from three phase 3 clinical trials of Eli Lilly’s investigational drug candidate tirzepatide, a dual GIP/GLP-1 agonist.
Data unveiled from the SURPASS-3 and -5 trials last week showed the drug was able to significantly drive down blood sugar levels as well as body weight at all three dosing levels tested. But it’s the lowest, 5mg dose, that will be “the workhorse of the franchise,” Gal wrote in a Monday note to investors.
From an efficacy point of view, the drug worked better as the dosage increased, with the 15mg version achieving the biggest reductions from baseline. But side effects such as nausea were also more pronounced for the higher dose strengths, Gal noted. Patients’ failure to stick to their therapies is already a major issue in diabetes treatment, he said.
“We tend to think of these doses as adding an option for motivated patients, but it’s tough to make these doses the ‘default options,’” he said.
Already, most patients are on lower doses of Ozempic and Trulicity despite the higher-dose regimens offering better efficacy, Gal said. When it comes to the low doses, tirzepatide appears to be a better drug than Ozempic, he added.
Tirzepatide has reported results for three pivotal trials, SURPASS-1, -3 and -5, in patients on different background therapy and on different control arm comparators. Compared with the respective Ozempic trials in similar settings—SUSTAIN-1, -4 and -5—tirzepatide at the 5mg dose looks “modestly better” on blood sugar reduction, Gal noted. But the weight loss benefit was much better for the Lilly drug.
For example, in SURPASS-3, where patients were already on metformin with or without an SGLT-2 inhibitor, 5mg tirzepatide helped patients achieve a 7kg (15.4lb) weight reduction from an average baseline of 94.3kg (207.9lb), versus a 1.9kg (4.2lb) gain for insulin takers.
In SUSTAIN-4 conducted in a similar patient population, 0.5mg and 1mg Ozempic delivered weight losses of 3.47kg and 5.17kg, respectively, off a baseline of 93.4kg, versus a 1.15kg gain for insulin receivers. Ozempic is currently approved for both those doses, and Novo’s seeking an FDA nod for an even higher 2mg dose.
On side effects, Gal noted the two drugs showed similar tolerability profiles after a similar titration period.
So, even though both drugs are able to achieve better efficacy at higher doses, their increasing side effects could make the lower doses the primary market—and that’s where tirzepatide has the advantage, Gal explained.
The guessing game could soon be over as ambitious Lilly is conducting the SURPASS-2 study, pitting tirzepatide directly against Ozempic. Gal said he will keep a close eye on the comparison of the 5mg tirzepatide to 1mg Ozempic, which he thinks will be the main commercial doses.
Currently, Lilly’s earlier-to-market Trulicity boasts a market share lead against Ozempic, holding U.S. total script share of 44.7% compared with 27.9% for Ozempic, according to a Novo presentation for its 2020 financial results. The two drugs are also competing neck and neck against each other on GLP-1 new-to-brand share; Trulicity had 38.5% as of January 2020, while Ozempic had 34.3%.
But Novo’s hoping to disrupt the market with its newly launched oral semaglutide offering, Rybelsus. As of January, the new drug had snatched 4.7% U.S. total GLP-1 script share, or 11.5% new-to-brand share. The drug seems to be attracting patients who’ve never taken a GLP-1 drug before, as over 80% of its new scripts are coming from this population, according to Novo.