Eli Lilly's Metabolic Medicine Leads Development of Oral GLP-1 Drugs
The next wave of metabolic drugs under development includes oral GLP-1 drugs that work comparable to currently available injectable drugs, while Eli Lilly leads with Phase 3 results, showing that its once-daily pills reduce blood sugar and weight in patients with type 2 diabetes.
Based on preliminary data from the drug, Lilly plans to seek regulatory approval for weight management by the end of this year before regulating drugs for type 2 diabetes in 2026.
Lilly is evaluating the program of the seven-stage study spanning type 2 diabetes and obesity or Foglia. The results reported on Thursday are the first of the 3-phase plan for the scope. The study used the drug as a monotherapy test in patients with type 2 diabetes. 559 study participants did not take any antidiabetic medications within 90 days before the first visit and had not received insulin treatment before.
The main trial goal was to show changes in hemoglobin A1c level, a measure of blood sugar. Lilly said Orfoglipron achieved this goal, with a 1.3% reduction in mean A1C at low doses, 1.6% reduction in mean A1C at medium doses and 1.6% reduction in mean A1C at high doses, according to Lilly. The A1C was reduced to 0.1% in the placebo group. Lily noted that more than 65% of patients receiving the highest dose of Orforglipron had A1C levels below or equal to 6.5%, below the American Diabetes Association’s threshold for diabetes.
On the key secondary targets for measuring weight, the maximum weight loss was observed in the high-dose group, with an average weight loss of 7.9% (approximately 7.3 kg or 16 lbs or 16 lbs), while the average weight loss in the placebo group and the average weight loss in the placebo group. At the end of the trial, this weight loss was not stable, which, for example, suggests that patients may lose more if they continue to use the drug.
Like other GLP-1 drugs, the most common adverse reaction is the gastrointestinal tract. For Li, these problems are classified as mild to moderate severity. The highest rate of discontinuation was 8%, reported in the highest dose group. Eli Lilly also said no liver safety signals were observed. This is noteworthy, as Pfizer stopped its oral GLP-1 pill Danuglipron earlier this week after patients experienced potential drug-induced liver damage.
For Li, more detailed trial results will be presented at the American Diabetes Association's scientific meeting in June. The company expects other Orforglipron trial readings later this year.
“As a convenient daily medicine, Orforglipron may offer a new option that, if approved, can be easily manufactured and launched on a large scale for people around the world,” Lily CEO David Ricks said in a prepared statement.
Currently available GLP-1 drugs are engineered peptides that must be used as injections. Novo Nordisk has sold the oral GLP-1 type 2 diabetes drug Rybelsus. The pill contains semi-citrus peptide, the same peptide that is the main component of its diabetes drug. Rybelsus is made by a technique that makes it possible to absorb peptides. For the technique to work, the medication must be taken on an empty stomach.
Orforglipron is a small molecule that does not contain food and beverage restrictions. Small molecules are also cheap to produce and do not require refrigeration, which gives them manufacturing and supply chain advantages over engineered peptides. The cost and complexity of manufacturing GLP-1 peptide drugs for diabetes and obesity has led to manufacturing shortages that have not been resolved until recently.
The clinical trial comparison of Orforglipron and Semaglutide is accompanied by all warnings related to cross-study. None of the diabetes studies at Novo Novo Drug are perfect comparators because the baseline measurements of A1C are different, and patients in these trials also continue to take dithyroxine, a standard diabetes medication, said David Risinger, an analyst at Leerink Partners. Nevertheless, he said the results of Eli Lilly's drug were favorable to Semaglutide.
In a study, William Blair analyst Andy Hsieh said the signs of this complication have become even more important in clinical trials given Pfizer's discontinuation of its drug due to hepatotoxicity. While William Blair awaits more detailed data, the company is comfortable with the lack of any signs of liver toxicity, which also validates that the candidate's molecular structure is similar to that of Orforglipron's candidates. The group includes drugs developed by structural therapy and AstraZeneca.
Hsieh also said investors may be enthusiastic about the numerical advantage of Lilly's oral medication compared to injectable Ozempic. But he added that there will still be one place for injections and market opportunities may vary by country.
“In the long run, we believe that these approaches may continue to dominate and occupy a large part of the market share driven by the relatively high potency of peptide-based subcutaneous delivery of drugs in higher-income countries.” “However, oral options that do not require refrigeration may be the best solution for middle-income or low-income countries that can provide health care as barriers.”
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