Read Part 1: Pharma's weight loss challenge: The incretin effect
Read Part 2: Pharma's weight loss challenge: Nourishing an obesity market
Shortages aren’t the only issue that manufacturers must lean into if the industry wants to upend the obesity epidemic.
According to ECRI, the biggest barrier to weight loss drug adoption is pharma’s familiar nemesis: price. Currently, Wegovy injections list for $1349 per month. The price tag means that most Americans can only access the next-gen medication through health insurance — and right now, coverage is a work in progress.
While most private insurance companies will cover the new incretin medications for patients with diabetes, those seeking out treatment for obesity are still battling historical biases in the form of plan exclusions.
On the public side, only nine states have placed GLP-1 weight-loss drugs like Wegovy on their Medicaid preferred drug lists. Medicare, however — under the Medicare Modernization Act, which passed in 2003 in the shadow of the Fen-Phen fallout — is prohibited from covering medications used for weight loss.
“Insurers’ unwillingness to cover weight-loss medication puts it out of reach, especially for people with low incomes who experience obesity disproportionately,” says Schabacker. “It’s really important to stress the point that the non-payment further drives the inequity in our health care system.”
Lawmakers recently reintroduced the Treat and Reduce Obesity Act (TROA), an 11-year-old bipartisan piece of legislation which, among other improvements, would expand Medicare Part D coverage to include FDA-approved anti-obesity medications. The bill has been endorsed by a host of medical groups including the Obesity Medicine Association and, not surprising, pharma companies such as Boehringer Ingelheim, Novo Nordisk and Eli Lilly.
With many private insurers modeling their benefits after Medicare coverage, the passage of a bill like TROA would have effects beyond just the senior population covered by federal insurance. But legislation still faces an uphill battle because the large potential patient population requiring long-term treatment translates to enormous government payouts. One NEJM perspective piece from health policy researchers at Vanderbilt University Medical Center calculated that if all Medicare beneficiaries with obesity were to be prescribed Wegovy, the cost would exceed the entire Medicare Part D budget.
The onus of course, can’t be placed entirely on payers. “Price is not determined by production cost. Price is determined by what the market bears,” reminds Schabacker. Yet with demand skyrocketing and supplies dwindling, patients are unlikely to see price reductions until more drugs are commercialized and competition ramps up.
As is typically the case with any new category of drugs, the pharma industry’s focus has been on payer coverage. The versatility of incretin mimetics and their potential to prove effective in additional conditions that are often linked to excess weight has helped upped the odds for pharma. Having learned lessons from the drugs that hit the market first, manufacturers are building their case in the clinic.
One example is Boehringer Ingelheim’s experimental once-weekly injectable, survodutide, born out of a longstanding partnership with Zealand Pharma and now advancing into phase 3 clinical studies in obesity. While the drugmaker says it’s too early to comment on pricing, Ioannis Sapountzis, global head of Therapeutic Areas at Boehringer Ingelheim advocates a more comprehensive view of treatment value.
“It is important to consider the long-term costs associated with obesity especially since it is a leading risk factor for several cardiovascular, renal and metabolic conditions,” says Sapountzis. “We are convinced that conversations with payers will evolve given the changing perception of obesity.”
In addition to obesity and type 2 diabetes, survodutide is also being tested in liver diseases such as non-alcoholic steatohepatitis (NASH). NASH, one of the major causes of liver fibrosis and cirrhosis, is especially prevalent in people with metabolic disorders such as obesity.
Eli Lilly is also studying Mounjaro as a potential treatment for NASH, as well as in sleep apnea and HFpEF, the most common form of heart failure.
Grabbing the obesity approval hasn’t stopped the research for Novo Nordisk, with the drugmaker’s 17,600-person SELECT trial proving a major win for semaglutide and GLP-1 agonists in general in terms of cardiovascular indications.
As drugmakers push to expand their incretin drug labels, their findings lend more evidence to the case for obesity as a serious medical condition in need of pharmacologic treatment.
“Studies like the SELECT trial are going to change this discussion,” says Lazarus. “Let’s say a patient comes to see a family doctor and has sky high blood pressure — ignoring it in this day and age would be malpractice. Similarly, I think we are getting to a point where we are going to have to address weight.”
Full pipelines
Whether attributed to the temptation of a looming $100 billion market or the genuine hunger to fill an unmet need for millions of patients, drugmakers have taken a seat at the obesity care table.
Citeline’s Pharmaprojects database found that globally, there are 51 active drugs in development with incretin mimetics as the mechanism of action. Within these compounds, 22 are being explored in obesity.
While the first drugs on the market were limited to single GLP-1 agonists, new drugs are pushing boundaries in incretin pathways as drugmakers pursue drugs with dual modes of action.
Boehringer Ingelheim-Zealand Pharma’s phase 3 drug, survodutide — which has demonstrated up to 19% weight loss in trials — is a dual agonist that activates both GLP-1 receptors and receptors for glucagon, a hormone that plays a role in energy balance through receptors in adipose tissue (body fat) and the brain.
“Survodutide has the potential to become the first anti-obesity medication to induce significant weight loss by reducing appetite while increasing energy expenditure through direct action on the liver to help people with overweight or obesity reduce their body weight,” says Boehringer’s Sapountzis.
Eli Lilly has a triagonist in phase 3 trials for obesity and diabetes. The asset, known as retatrutide, activates receptors for GLP-1, glucagon and GIP.
“The incretin-based treatments that are currently approved to treat obesity only activate the body’s receptors for GLP-1. We believe combining glucagon receptor agonism with GIP and GLP-1 receptor agonism may contribute to higher levels of reduction than that seen in trials for single- or dual-receptor agonists,” says an Eli Lilly spokesperson.
Another trending area in the clinical space has pharma squaring off against a long-established challenge — converting injectable drugs to shelf stable, oral medications. Currently, the only GLP-1 medication offered in oral form is Novo Nordisk’s Rybelsus, a once-daily pill version of semaglutide, approved for type 2 diabetes.
In 2020, Novo acquired Emisphere Technologies and its proprietary drug delivery technology known as Eligen sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC). The technology, used in the Rybelsus formulation, is an acylated amino acid designed to improve the oral bioavailability of parenteral drugs. SNAC enables the transport of therapeutic molecules, including large peptides and proteins, across biological membranes, such as those of the gastrointestinal tract — a notorious stumbling point for oral biologics.13
Both Novo and Lilly are advancing once-daily oral GLP-1 receptor agonists in phase 3 trials for obesity and Pfizer has a twice-daily oral obesity drug in mid-stage trials.
The oral formulations have shown comparable efficacy to their subcutaneous counterparts and the needle-free administration is a major selling point with patients. But the drugs still come with some hurdles. Novo Nordisk’s oral semaglutides, for example, must be taken on an empty stomach with only a sip of water, and patients must wait 30 minutes before intake of food or other medications.
However, for drugmakers, oral formulations have established manufacturing, storage and distribution advantages that will not only result in lower costs but could ultimately facilitate a more global availability of much-needed anti-obesity drugs.
The big reveal
“The standard of care for the treatment of obesity in primary care has essentially been to do nothing,” says Dr. Lazarus. “Ignoring the problem is really missing the mark in terms of offering patients evidence-based treatments.”
But after hundreds of years of stagnating treatment, a critical moment for obesity care hangs in the balance — and incretin mimetics could tip the scales in a very big way.
“People living with obesity deserve action, not just hope. The stakes are too high to let another 10 years go by without more change,” wrote Eli Lilly in a recent blog post.
With the final piece of the multifaceted approach needed to combat obesity in its hands, all eyes are on the pharma industry. What the industry does next in terms of facilitating access to this innovative new class of anti-obesity treatments has the potential to not only better the health of millions, but forever transform the way the world views obesity.
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