Ease of Use, Higher Efficacy Drive Lilly’s New Diabetes Treatments

 

Diabetes and obesity remain a problem, even during a pandemic. Eli Lilly is continuing to develop the 13 diabetes drugs it has in Phase I through Phase III trials, with data from various trials planned for release throughout the coming year. 

Michael Mason, SVP & president of Diabetes & Connected Care for Lilly, discussed some of these programs during the UBS Global Healthcare Virtual Conference May 19. Recurring themes were increasing new drugs’ ease of administration and efficacy, opportunities for expanded indications – notably for obesity and NASH – and combination therapies.

As restrictions related to the COVID-19 pandemic ease, the company is thinking about growth. The GLP-1 class of diabetes therapies, which includes Trulicity® (dulaglutide), is a good example. Despite being introduced as a new drug class a decade ago, it has an annual growth rate of 35%.

The REWIND trial of once-weekly injections of Trulicity shows a 12% reduction in major cardiac events. Lilly began promoting results from the REWIND trial of Trulicity to physicians in mid-May, detailing its use for both secondary and primary prevention.

“There’s amble opportunity to grow, and to grow earlier,” Mason said. One of those opportunities involves higher doses. “People want to stay on Trulicity,” Mason said, but eventually many need greater efficacy. Higher dose versions, “whether oral or injectable” enable that. Another opportunity expands the indications to include obesity, based on studies indicating that Trulicity contributed to a 10 pound weight reduction in obese patients.

Currently the drug is being evaluated by China for possible inclusion on its National Reimbursed Drug List (NRDL). “We don’t have clarity on when China will make that decision. Hopefully, it will be this year,” Mason said.

Another new diabetes drug, Tirzepatide, is expected to deliver a Phase III reading later this year. Mason said he expects to see greater efficacy and better tolerability – particularly in the form of fewer gastrointestinal side effects – than during the Phase II trial.

Dose escalation, a concern expressed by the USB moderator, is not an issue, Mason said. In trials, initial doses may not be effective until safety and tolerability are ascertained. By Phase III, those concerns have been addressed. Therefore, for real world applications, “The starting dose of Tirzepatide is efficacious,” Mason said. Administration is weekly, and easy.

Tirzepatide also is being studied to treat NASH and related conditions, such as obesity. Although Wall Street is skeptical, payers seem interested in therapies for such applications. It is closely related to obesity, pre-diabetes, and diabetes.

“There are approximately 16.5 million people in the U.S. living with non-alcoholic steatohepatitis (NASH) and there’s been an incredible investment by pharmaceutical companies in treatments,” Mason pointed out. “We have the opportunity to treat a large segment of that population.”

Lilly is betting on a metabolic approach to this metabolic disease.

“If you affect weight loss, you should affect NASH progression,” Mason said. Tirzepatide is expected to be a good option because it contributes to weight loss and, thus, liver health. “We’re confident the market will be there.”

Studies of Tirzepatide also have shown a small improvement in fibrosis compared to placebo.

“Fibrosis is the last outcome in the NASH cascade, so with a longer trial, you’ll see results,” Mason explained. He suggested that a GLP-1 class drug combined with Tirzepatide could provide a significant benefit.

For the past decade, obesity agents have been eschewed by payers and physicians, Mason acknowledged. “It’s hard, therefore, for them to get out of that mindset, but the availability of dramatically different treatments could unlock access.”

That’s especially true of payers who are mining prescription and medical data to correlate therapies to outcomes. Approved weight loss therapies may confer a 5 pound benefit, whereas Tirzepatide and other new agents often contribute to weight losses of 10 or 15 pounds, which makes them more attractive to payers.

Mason also touched on some of the drugs in Lilly’s Phase I pipeline.

“We’re really excited about the tri-agonist we call Triple G. It’s a GLP, GIP and glucagon agonist that we think could induce more weight loss than Trizipide,” Mason said.

He expects to get Phase I results this year and, hopefully, start Phase II trials in 2021. The company also is developing an oral GLP-1 that Mason said offers better administration than Novo Nordisk’s Rybelsus®.

These therapies are for the future. Currently, the world is in the grip of the COVID-19 pandemic, and many patients are curtailing doctor visits. In the U.S., physicians are seeing about 30 percent fewer diabetes patients now than before the COVID-19 pandemic began. “The rapid decline that occurred early in the pandemic has bottomed out now,” Mason said, and seems to be reversing.

The rapid decline, however, meant that new-to-brand prescriptions for Lilly’s diabetes drugs also declined about 30 percent. In contrast, standing prescriptions for insulin declined only 15 to 20 percent, Mason said. Now that states are beginning to reopen, he predicted the number of prescriptions written gradually will return to pre-COVID-19 levels.

That experience is reflected broadly throughout the world. In China, for example, “It took six to eight weeks for physicians’ offices to reopen. The impact of COVID-19 was more dramatic on new-to-brand prescriptions, but prescriptions are still 15 to 20% below pre-COVID-19 levels.

The long-term effect on diabetes therapeutic sales in the U.S. remains to be seen, Mason said.

“It depends on how long the crisis lasts, where employment levels gets to, whether those levels are maintained, and what the government does regarding economic stimulus,” Mason said.