Eli Lilly Delays Retatrutide Filing, Pursues Biologics Application

Eli Lilly announced Thursday that it will submit its obesity drug retatrutide for U.S. regulatory approval in the first quarter of 2027, pushing back an earlier expected timeline. The company is pursuing a Biologics License Application (BLA) rather than a conventional new drug application, a move that involves more complex manufacturing and quality-control requirements but could provide longer market exclusivity and stronger protection against biosimilar competitors.

The decision followed positive results from two additional Phase 3 trials. In the Triumph-2 study, which enrolled 1,152 participants with obesity and type 2 diabetes, patients receiving the highest 12 mg weekly dose lost an average of 20.8% of their body weight — roughly 49.6 pounds — over 80 weeks and reduced A1C levels by up to 1.6 percentage points. In the Triumph-3 trial, adults with severe obesity and established cardiovascular disease lost up to 22.6% of their body weight, or about 55.8 pounds, over the same period, with improvements in cardiovascular risk factors including triglycerides, non-HDL cholesterol, systolic blood pressure, and waist circumference.

Retatrutide is an experimental weekly injection that simultaneously targets three metabolic hormones — GLP-1, GIP, and glucagon — distinguishing it from existing treatments. Lilly’s current blockbuster Zepbound acts on two hormones, while Novo Nordisk’s Wegovy targets only GLP-1. If approved, retatrutide would be the first triple-agonist medicine on the market.

Cardiovascular data presented a mixed picture. While major cardiovascular events occurred less frequently than expected in both the treatment and placebo arms, an analysis of the three most severe endpoints — heart attack, stroke, and death — showed patients on retatrutide had a 12% higher risk compared to placebo, though the limited dataset may raise questions. The most common side effects were diarrhea, nausea, and constipation, consistent with previous studies.

Lilly has been fighting for biologic classification for retatrutide because the drug’s amino acid structure sits on the boundary of the federal definition of 40 amino acids. The company filed a complaint in federal court in 2024, and a judge last year ordered the FDA to reconsider its narrow interpretation. Retatrutide now has positive results from five Phase 3 trials.

The BLA pathway is typically reserved for products like vaccines and gene therapies. A Complete Response Letter (CRL) can be issued if the FDA finds that an application cannot be approved in its current form due to manufacturing, clinical, or labeling deficiencies. Meanwhile, a recent report from the Senate HELP Committee recommended creating a middle ground between a full BLA and an abbreviated BLA, aiming to increase competition and accelerate patient access to biologic medicines.