SELECT Trial Data On Weight Loss Drug Wegovy May Not Be Enough To Convince Payers

Data presented at a meeting of the American Heart Association on Saturday indicates cardiovascular protective benefits from taking the weight loss therapeutic Wegovy for a sub-population with preexisting cardiovascular disease. But the absolute risk reduction is quite small. Payers will take notice of this in addition to the timing aspect with respect to when the benefits accrue, the non-generalizability of the data, the high price of Wegovy per patient and the potentially substantial financial exposure they incur if they cover the drug.

A full dataset presented at the annual Scientific Sessions meeting of the American Heart Association on Saturday suggests that the GLP-1 obesity drug Wegovy (semaglutide) decreased relative risk by 20% of a composite primary endpoint measure which included death from cardiovascular causes, non-fatal myocardial infarction and non-fatal stroke. Specifically, Wegovy reduced the risk of non-fatal heart attack by 28%, non-fatal stroke by 7% and heart-related death by 15% compared to placebo.

But the data didn’t show Wegovy decreased the risk of cardiovascular death by a statistically significant margin. Researchers didn’t carry out formal statistical testing on other individual secondary endpoints, such as heart failure complications, non-fatal heart attacks and death from any cause. They merely provided estimates of benefit that “should not be used to infer definitive treatment effects.”

The large randomized controlled clinical trial named SELECT, upon which the analysis was based, included overweight and obese study participants with preexisting cardiovascular disease. This was not a typical overweight or obese sub-population. The trial subjects were at very high risk for subsequent cardiovascular events with 68% having had a previous heart attack, 82% with coronary artery disease, and the remainder with prior stroke or peripheral arterial disease or a combination of these study entry criteria. In addition, the average body mass index of enrollees was over 33 kg/m2 and the mean age at entry was 62.

Besides the trial sub-population being at severe cardiovascular risk, 72% were male, 84% Caucasian and 66% had A1c levels over 5.7 indicating prediabetes. It’s evident therefore that the data from the SELECT trial are not generalizable.

Clearly more research is required to resolve the question of cardiovascular benefits conferred by GLP-1 drugs for people who are overweight or obese but without prior heart attacks or other high risks for cardiovascular events and who are female and non-white.

Furthermore, regarding the primary endpoint, the diminished number of cardiovascular events implies an absolute reduction of only 1.5 per 100 people in a high cardiovascular risk cohort, taking Wegovy for more than three years. In other words, 98.5 of every 100 high-risk persons on Wegovy for more than three years didn’t show a reduction of cardiovascular events.

Payers will take notice of the small absolute reduction in risk, the lack of generalizability of the data, the very high price per patient and how much impact coverage of Wegovy will have on budgets.

Every healthcare dollar has an opportunity cost. It can’t be spent twice. With a potentially very large budgetary impact, payers must carefully calibrate their reimbursement policies to optimize the value associated with what they spend on prescription drugs. This could mean non-coverage for certain patients who are otherwise indicated for a particular drug or different degrees of coverage for patients stratified into various sub-groups.

Here the timing aspect of when the cardiovascular benefits accrue will also play a role. It appears that the weight loss benefit begins to occur soon after the first prescription is filled and taken by the patient. But the cardiovascular benefits take longer to emerge and reach a critical level.

It’s important to be cognizant that payers often have a short time horizon due to so-called churn or turnover of enrollees at commercial, Medicaid and Medicare plans. This can happen as frequently as once every one to one-and-a-half years. So payers may be reluctant to foot the bill for benefits which don’t manifest themselves under their watch.

There may also be other payer concerns including a lower weight loss figure of 9.4% than in previously posted Wegovy studies. And the side effect profile remains an issue. Muscle mass and bone density loss are serious concerns payers have, particularly since they’re not rare events associated with semaglutide-based agents. And of course the common side effects of nausea, vomiting and diarrhea can be a problem, too. It was enough of an issue that 17% of trial participants dropped out. In the real world this number is likely to be higher. Discontinuation was in fact much higher in a real-world observational study published in July. When a patient stops taking semaglutide-based products for obesity they get weight rebound.

All things considered, there are a number of caveats which payers will likely bear in mind when reviewing the full SELECT dataset, particularly in light of the very high monthly price and the need for patients to take the medications indefinitely. In this regard, it behooves clinicians to come up with sophisticated strategies of weaning and discontinuation of the weight loss medications to avoid the known side effects and also those that may appear after extended exposure.

It’s notable that this year some health insurers have been pulling back on coverage of obesity medications, according to a recent survey published by the obesity care provider Found. Evidently, the results are consistent with national trends in coverage for these products.

When insurers clamp down on coverage it could mean outright reimbursement denials. But it can also imply more subtle ways of limiting their financial exposure. These include the use of step edits to discourage doctors from prescribing the more expensive drugs first; or requiring pre-authorization, usually in the form of a specific diagnosis and data on the patient, such as the presence of co-morbidities before dispensing and reimbursing a product.

Health plans may also institute duration or quantity limits, capping the length of time that a drug will be reimbursed. Just this week the Mayo Medical Plan, which covers Mayo Clinic employees, announced it is instituting curbs on coverage of products such as Wegovy. This includes a lifetime $20,000 cap on payer spending per patient on weight loss agents. Effectively this amounts to a duration limit.

It’s unclear whether publication of the SELECT trial data will halt the trend in payer utilization restrictions or non-coverage. It is possible that some payers who had been on the sidelines until now—not yet including the new classes of obesity drugs on formulary—will soon offer access to semaglutide-based therapeutics for obese patients who are at severe cardiovascular risk. At the same time, payers will tread cautiously, instituting utilization restrictions while monitoring the real-world data that emerges on effectiveness and adverse events.