Are Obesity Drugs the Next Blockbusters?

Obesity is considered an epidemic of 21st Century. Due to an increasingly sedimentary lifestyle and unhealthy food consumption, obesity affects both adults and children. Weight gain is not just an aesthetics problem; it leads to higher risk for cardiovascular diseases and diabetes. Overall, the potential burden on the healthcare system is multiplying. To date, solutions offered by pharma companies are far from optimal. However, despite insurance opposition, current new medications show more exciting outcomes for weight loss. Can these new drugs be the next blockbusters in the obesity space?

Who: winners and losers?

Weight-loss and obesity are one of the most discussed topics in society. It is becoming even more popular due to the fact that the prevalence of this condition is increasing steadily. Statistics from the Centers for Disease Control and Prevention (CDC) show that the prevalence of obesity in the United States increased from 30.5% to 41.9% from 2000 to 2017 (1).

It is also well-established fact that excess of weight leads to other health-related conditions such as heart disease, stroke, and type 2 diabetes. This in turn translates into healthcare costs that are a burden even for developed countries: in 2019 the annual medical cost of obesity in the US was estimated at nearly $173 billion.

Surprisingly, obesity is considered by medical community more of a behavioral problem that can be treated in most cases by diet and exercise. And yet, many people despite being active or eating healthy fail to lose excessive weight. More research shows that genetics, sedimentary lifestyle imposed by our jobs, and age all contribute to difficulties to slim down and reach a healthy weight profile.

This is where weight-loss medicines are coming into play. However, despite years of research, it has become obvious that an effective weight loss drug is not easy to develop; one of the obvious examples being fen-phen. This combination of fenfluramine and phentermine was considered a miracle drug until it was shown to cause heart valve problems causing patient deaths, which led to billions of dollars in lawsuits (2). The drug was taken off the market.

Another example is Xenical prescription (marketed by Roche) (3) and over-the-counter (OTC) product Ali (marketed by GSK) (4). Once again, its side effects (diarrhea, oily stools) were much stronger than its benefits. Many believe that researchers downplayed the frequency of these side effects. Consequently, the market responded and from $600 million sales per year in the end of the 1990s, prescriptions of Xenical declined every year (5).

New weight loss options on the market are Contrave (a combination of antidepressant and anti-addiction drug) that is distributed by Currax and Qsymia marketed by Vivus. Approved by FDA in 2022 (6), Qsymia is a combination of phentermine/topiramate. However, it has potential side effects, while success of the medication in weight loss is not assured.

Currently, the unquestionable leader in anti-obesity market is Novo Nordisk. Wegovy (semaglutide) was approved by FDA in 2021 as anti-obesity drug (7). This glucagon-like peptide 1 receptor agonist is a higher dose of Novo’s successful diabetic drug Ozempic.

Because the drug showed impressive clinical data unlike other options on the market (33% of patients lose more than 20% of their body weight), sales projections for the drug by 2025 are doubled. Just in three month of 2021, it generated more than $100 million and is expected to reach billions in sales in the next five years.

What: leading innovators

Indeed, Novo Nordisk can be considered an innovator in the weight loss space. Unlike previous medications on the market that target brain functionality in hunger control (Contrave, Qsymia), Novo went for a different route. It works on glucagon-like peptide 1 receptor (GLP1R) responsible for insulin resistance. GLP1R controls blood sugar level by enhancing insulin secretion. Glucagon-like peptide 1 (GLP-1), a gut hormone, is released in response to meal intake stimulating insulin secretion (8).

Initially, Novo developed Semaglutide (Ozempic), which acts like human GLP-1 and increases insulin secretion, thereby accelerating sugar metabolism. Wegovy, a higher dose of the same Semaglutide, seems to control the hunger as well as sugar metabolism leading to weight loss in obese patients.

When: new arrivals

The idea of GLP1R as a target attracted other pharma. In 2023, Eli Lilly and Company also intends to enter the anti-obesity market. They have developed Tirzepatide, once-weekly glucose-dependent insulinotropic polypeptide (GIP) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist that integrates the actions of both incretins into a single novel molecule. SURMOUNT-1 clinical trial shows that patients can lose more than 20% of body weight, results comparable to bariatric surgery (9).

In May 2022, the company got FDA approval to use Mounjaro (tirzepatide) injections, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Now Eli Lilly and Company is pursuing approval for weight loss. If approved, the company will represent strong competition to Wegovy with a potentially superior clinical outcome (10).

Why:pluses and minuses

Novo had to revamp its production due to high demand for Semaglutide and some setbacks with manufacturing facilities (11). Overall, reliable API suppliers and contract manufacturing organizations (CMOs) are key factors in market success.

Indeed, to solve such potential manufacturing obstacles, many companies opt to build in-house capabilities instead of relying on CMOs. Novo decided to build three new manufacturing facilities. This step will increasemanufacture of its APIs, while also being able to assemble and package the oral and injectable products (12).

Eli Lily, a new potential player in obesity market, seems to understand manufacturing challenges. They plan to expand manufacturing footprint in Indiana by investing $2.1 billion in two new manufacturing sites (13).

Another outstanding issue is cost of medication to patients. Qsymia is an example; initial sales of the product were disappointing due to the high cost of medication and reluctance from insurance to cover this cost (14). The reason is that many health insurers view obesity treatments as behavioral issue and lifestyle medications. Consequently, they’re unenthusiastic to provide reimbursement.

Even Big Pharma companies such as Novo Nordisk admitted that Wegovy access and reimbursement will be challenging. It is in industry’s interest to move payer perception of obesity: changing it from a lifestyle issue to a chronic disease. However, one of the pluses of this approach is that clinical benefits for medication such as Wegovy can lead to a reduction in other comorbidities associated with obesity and overall healthcare spending.

Food for thought

Considering that obesity has become an epidemic of the developed world, the earning and growing potential of this market is remarkable. More importantly, obesity treatments can be considered as healthcare preventive medicine.

Nevertheless, drugs like Wegovy or Mounjaro will not solve weight problems for every person. More research shows that metabolism is a complex issue and hunger reduction is not the only approach to treat patients. Research on “brown” fat, leptins, adiponectin, and other fat/sugar processing mechanisms suggests that weight gain is a complicated topic (15).

Despite headwinds, obesity drugs are obviously making an impact in the pharma markets.

References

1. CDC, “Adult Obesity Facts,” cdc.gov, May 17, 2022.
2. D.J. Morrow, “Fen-Phen Maker to Pay Billions In Settlement of Diet-Injury Cases,” The New York Times, October 8, 1999.
3. M. Malone, IDrugs 1(2), 232-41 (1998).
4. Mayo Clinic, “Alli Weight-loss Pill: Does it Work?”, Mayoclinic.org, March 12, 2022.
5. R. Robbins, “A Popular Weight-loss Pill was Buoyed by Studies that Understated its Harms,” statnews.com, August 16, 2016.
6. Vivus, “FDA Approves QSYMIA for the Treatment of Obesity in Adolescents Ages 12-17,” Press Release, July 20, 2022.
7. FDA, “FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014,” Press Release, June 4, 2021.
8. J.J. Holst, Physiol Rev 87(4), 1409-39 (2007).
9. Eli Lilly, “Lilly's Tirzepatide Delivered up to 22.5% Weight Loss in Adults with Obesity or Overweight in SURMOUNT-1,” Press Release, April 28, 2022.
10. Eli Lilly, “FDA Approves Lilly's Mounjaro (tirzepatide) Injection, the First and Only GIP and GLP-1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes,” Press Release, May 13, 2022.
11. Novo Nordisk, “Novo Nordisk Announces Supply Challenges for Wegovy in the US,” Press Release, Dec. 17, 2021.
12. Novo Nordisk, “Novo Nordisk Invests More than DKK 17 bn in Expansion of the Manufacturing Facilities in Kalundborg, Denmark,” Press Release, Dec. 12, 2021.
13. Eli Lilly, “Lilly Plans to Invest $2.1 Billion in New Manufacturing Sites in Indiana,”Press Release, May 25, 2022.
14. DietsInReview, “Qsymia Sales Prove Disappointing Thus Far,” dietsinreview.com, Nov. 7, 2021.
15. H. Wein, “How Brown Fat Improves Metabolism,”nih.gov, Sept. 10, 2019.

About the author

Marina Necdina is a business development manager, former pharma analyst, and research scientist.