04/16/2026  |  Annabel Kartal Allen  |  Clinical Trials Arena

https://www.clinicaltrialsarena.com/news/fda-requests-postmarketing-safety-studies-eli-lilly-foundayo/ 

The regulator requires Lilly to evaluate the “unexpected serious” risks associated with Foundayo.

li Lilly has released more data for its obesity pill, Foundayo (orforglipron) in a rapid response to US regulators voicing certain reservations on the therapy’s safety.

In a new drug application (NDA) approval letter sent to Lilly by the US Food and Drug Administration (FDA), the agency requested that the pharma conduct clinical studies evaluating Foundayo’s safety profile across the general population, while homing in on the drug’s impact on younger paediatric and pregnant patients.

The FDA’s request comes as the agency airs concerns around early safety signals exhibited by Foundayo that cannot be dissipated through nonclinical or observational studies – including the alleged capacity for the drug to enhance a patient’s risk of major adverse cardiovascular events (MACE), drug-induced liver injury (DILI) and a type of thyroid cancer.

Since the FDA debuted this letter, Lilly has shared results of the Phase III ACHIEVE-4 trial (NCT05803421), which found that patients taking Foundayo were at a non-inferior level of risk for MACEs – including heart attack, stroke, cardiovascular death or sudden chest pain – compared with insulin glargine. There was also no safety signal around liver toxicity detected in this study.

Based on these results, the pharma is teeing up approval for Foundayo in type 2 diabetes, with plans to submit a new drug application (NDA) for the therapy to the FDA by the end of Q2 2026.

While the ACHIEVE-4 study points to Foundayo’s favourable cardiovascular risk profile, the FDA is also looking for proof of the drug’s safety in both patients aged between six and 12, and pregnant individuals, due to the agency’s observation of “unexpected serious” risks associated with its long-term use. Studies in the latter patient population will look at outcomes in mothers and foetuses, as well as infants exposed to Foundayo in the womb and through breastfeeding.

Additionally, Lilly must collate more data on Foundayo’s impact on the incidence of medullary thyroid carcinoma over a 15-year period.

Eli Lilly first secured approval for Foundayo through the Commissioner’s National Priority Voucher (CNPV) scheme. When the FDA debuted the CPNV initiative, it was met with industry uncertainty, as many noted the requirements to obtain a voucher were “unclear”.

ACHIEVE-4 data puts analyst’s mind at rest
Before the debut of the ACHIEVE-4 data, some industry experts raised concerns about how these FDA requirements may impact the success of Foundayo in the long-term.

However, following the publishing of these results, Shehroz Mahmood, senior obesity analyst at GlobalData, noted that the demonstration of cardiovascular non-inferiority and confirmation of no hepatic safety signal “neutralises these concerns” while validating Lilly’s readiness to manage post-marketing surveillance.

According to Mahmood, the post-approval liver monitoring requirements should not substantially hinder Foundayo’s commercial uptake or competitive positioning against Novo Nordisk’s oral Wegovy (semaglutide).

“The FDA’s requests represent standard post-marketing commitments for drugs approved through expedited review rather than label-altering safety warnings and were expected in the absence of long-term diabetes safety data, as seen with oral semaglutide, which benefited from years of Rybelsus experience before Wegovy pill approval,” Mahmood added.

As Lilly has proactively disclosed data demonstrating no safety signals across the entire development programme, Mahmood believes that Foundayo is positioned to compete on its key advantages of convenience and supply scalability, rather than being “constrained by safety perception gaps”.