Eli Lilly has shown patients maintained most of their weight loss after switching from injectable GLP-1s to its oral drug candidate, teeing the drugmaker up to target people taking Novo Nordisk’s Wegovy.
Lilly has filed for FDA approval of its oral GLP-1 receptor agonist, orforglipron, using data in patients who received the small molecule as an initial treatment for obesity. But the Big Pharma spotted a chance to piggyback on its head-to-head study of Wegovy and Zepbound to establish orforglipron for maintenance use. Patients who finished the trial were offered the chance to re-randomize to orforglipron or placebo.
After 52 weeks of daily oral dosing, patients who received Wegovy in the head-to-head trial had gained 0.9 kilograms. The patients weighed 113.5 kg before taking Wegovy, 95 kg at the end of the head-to-head trial and 95.9 kg after 52 weeks on orforglipron.
People who received Lilly’s Zepbound in the head-to-head trial regained 5 kg on orforglipron. The figures for that cohort are 115.8 kg at baseline, 90.9 kg after the Zepbound study and 95.9 kg after 52 weeks on orforglipron. All the figures come from per-protocol-like analyses focused on patients who stayed on the assigned treatment. Lilly is yet to share figures for analyses including patients who stopped treatment.
The drugmaker said the most common adverse events on orforglipron were gastrointestinal-related and generally mild to moderate in severity. Discontinuation rates due to adverse events were 4.8% and 7.2%, respectively, for patients who went from Wegovy or Zepbound to orforglipron. Discontinuation rates in the placebo cohorts were 7.6% and 6.3%.
Writing in a note to investors in October, BMO Capital Markets analysts said the readout on orforglipron in the maintenance setting was underappreciated. The analysts said the trial was a “unique opportunity” to win market share from Novo. Lilly could use the data to drive switches from Wegovy to orforglipron, chipping away at sales of its main rival’s flagship product.
Ken Custer, Ph.D., president of cardiometabolic health at Lilly, discussed the opportunity on an earnings call in October. Lilly has very bullish expectations for orforglipron as a first-line starter incretin, Custer said, and sees maintenance use as “an exciting boost” beyond those forecasts. Although patients could switch from Zepbound to orforglipron, Custer said Lilly doesn’t see the oral option cannibalizing injectable sales.
Lilly has a Commissioner's National Priority Voucher that could accelerate FDA approval of orforglipron. Novo’s oral form of Wegovy is in line to beat orforglipron to market. However, Lilly could have a supply edge because production of orforglipron, a small molecule, may be more scalable than manufacture of Novo’s relatively high-dose peptide.