Eli Lilly is offering expanded access to retatrutide, its investigational triple hormone receptor agonist that demonstrated substantial weight loss in phase 3 studies, and not all clinicians are happy about the move.

“For a limited number of patients who meet specific medical criteria and cannot enroll in a clinical trial, we believe it is medically appropriate to make authentic retatrutide available before FDA approval, consistent with FDA’s guidance,” a Lilly spokesperson said. “We’ve built an expanded access program that does that and are actively reviewing requests from healthcare providers.”

Eligible patients must meet all the following criteria:

• Age 18 years or older
• Refractory obesity, defined as BMI ≥ 35 despite adherence to and tolerance of treatment with highest available dose of chronic weight management therapy
• Two or more serious or life-threatening obesity-related complications for which the patient is currently receiving standard of care
• Unable to participate in an ongoing clinical trial of retatrutide or a similar/comparable investigational medicine (due to trial eligibility criteria or lack of a reasonably accessible enrolling site)
• All standard treatment options including bariatric surgery discussed with the patient through shared decision-making

‘Wild West?’

Clinicians had mixed responses to Lilly’s move. Here’s what they told Medscape Medical News: 

Priya Jaisinghani, MD, an obesity specialist at NYU Langone Health, New York City, said, “Expanded access programs have long been used in other areas of medicine. Applying a similar framework to refractory obesity marks an important milestone in recognizing obesity as a chronic disease and expanding options for patients living with this refractory disease and complications who have exhausted approved therapies. This program offers a potential treatment option while regulatory review continues.”

Michael Weintraub, MD, also an obesity specialist at NYU, noted that the FDA’s rigorous testing requirements to ensure safety and efficacy for any new drug are “particularly important for obesity treatment, where long-term treatment is necessary.”

“Traditionally, a drug would not be available until it could meet this high bar,” he told Medscape Medical News. “But the public has never before been exposed to such an onslaught of social media influencers and availability of unapproved and untested products. These compounded products are from an unknown source, without any assurance of quality, purity, or drug concentration. People are obtaining untested products without being told about the risks.”

“If the only choices were people going outside the medical system and getting untested compounded products vs receiving them from a reliable drug manufacturer with an FDA-regulated production process, I’d pick the latter,” he said.

“I would still exercise caution in prescribing an unapproved medication,” he added. “However, it would be less harmful for a drug to be offered to patients within the clinical setting, where monitoring for side effects or rare adverse events can occur.”

Amy E. Rothberg, MD, director of the Weight Management Program & Rewind at the University of Michigan, Ann Arbor, Michigan, questioned the move. “What is the motivation to allow early access? What do they mean by ‘we believe it’s medically appropriate?’ Who is vetting these patients, taking a medical history, performing a physical exam, looking at their medication profile? Who is monitoring these patients for weight loss, adverse effects?

“What is the rush prior to FDA approval? It will create confusion among patients and providers, who can have access, how to access and it will create a potential avalanche of patients asking for it, including those who may want to move from something they are already taking and had been managing and doing well on to a drug that is marketed for an even greater percent weight loss, likely creating a lot of unmet expectations.”

Ajay Rao, MD, chief of Endocrinology, Diabetes and Metabolism at the Lewis Katz School of Medicine at Temple University, Philadelphia, said “It is always difficult to prescribe items that have not been fully approved by the FDA. Most of us respect the rigor that the FDA goes through when approving things, but I think this clearly shows the anticipated need and potential benefits of the drug that have already been released in scientific meetings.

“I am always concerned when a medicine comes to use without full FDA approval but clearly there is a limited group that will be actually eligible in this early vanguard phase [and] prevents patients from getting compounded versions that are not made by Lilly.”

“I believe it does set a precedent within this drug class and wonder if this will become the norm for further agents in this space. I think the limited access program will hopefully prevent the agent from being used inappropriately.”

Like Rothberg, he said the move will “absolutely cause an avalanche of patients asking for it.”

Sara Ghoneim, MD, Massachusetts General Hospital, Boston, and an American Gastroenterological Association spokesperson, noted that expanded access “is a long-standing and legitimate FDA pathway. What matters clinically is that the criteria are narrow, applied consistently, and don’t divert patients who would be better served by enrolling in a trial.”

“For most people with obesity,” she said, “the right answer remains the approved therapies we already have and can monitor properly.”

Courtney Younglove, MD, Heartland Weight Loss, Overland Park, Kansas,said, “It’s a great option for patients with refractory obesity. Hopefully some of them will respond to a different drug with a different mechanism of action, which may give us some insight into why some people are non-responders.”

But while the criteria for approval into the program “are appropriately strict,” she said, “it’s likely that many people won’t pay attention and will flood our offices with requests to appeal on their behalf. And making one of the criteria that they have to be ineligible for a clinical trial for retatrutide assumes that all of us practicing know trial sites and eligibility, which we don’t.”

“Dropping it like this makes Lilly look like a hero,” she said. “But when patients don’t qualify or when we can’t keep up with demand for applications/appeals or check all the boxes (because we don’t have in-depth, easy access to the clinical trial information), we are going to look like like the bad guys.”

“To me, this feels like a marketing ploy designed to get people excited about the drug in advance of FDA-approval, to put more money in Lilly’s pockets, now and in the future,” she concluded.

Expanded Access Requirements

The FDA told Medscape Medical News that generally, “it cannot confirm or deny the existence of, or comment upon, any pending INDs (investigational new drugs) that have not been publicly disclosed by the sponsor. This applies equally to expanded access requests for single patient INDs.”

A physician seeking use for their patient through the FDA’s expanded access or “compassionate use” program, is responsible for confirming that the drug company will provide the investigational medical product. In addition to providing the product, the company either sponsors the expanded access, allows the FDA to cross-reference to their IND on behalf of the expanded access physician through the use of a letter of authorization, or provides the necessary investigational medical product information for the physician to submit to support an expanded access request.

Jaisinghani disclosed consulting for Eli Lilly, Novo Nordisk, Madrigal, and Corcept. Rothberg declared being a member of Boehringer Ingelheim’s advisory board for MASLD/MASH, being a Lilly speaker on a panel on diabetes remission, and conducting a clinical trial of CGM (money paid to her institution). Younglove is on a women’s health advisory board for Zealand. Ghoneim, Rao, and Weintraub declared having no conflicts of interest.

Marilynn Larkin, MA, is an award-winning medical writer and editor based in New York City whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.