What’s weighing down the billion-dollar obesity drug market?

 

The numbers are almost redundant at this point, but here we go: More than two-thirds (70.7 percent) of U.S. adults are considered to be overweight or obese, according to the Centers for Disease Control and Prevention (CDC). Close to 40 percent are obese, possessing a BMI of 30 or above.

It’s a disease that impacts health in myriad ways and it’s crushing financially. A 2014 McKinsey & Company report put the global economic burden of obesity at $2 trillion a year, a figure that is rapidly rising. Not surprisingly the U.S. domestic market for weight-loss products is also huge. Marketdata Enterprises estimates consumers spend around $60 billion a year on largely unproven goods and services.

When all of these figures and factors combine, one perplexing question remains: Why oh why have multiple FDA-approved weight-loss drugs largely failed?

Doctors aren’t prescribing them
Michael Narachi has watched the field evolve since 2009, as president and CEO of San Diego, California-based Orexigen.

After jumping through many hoops, Orexigen’s weight-loss drug Contrave was approved by the FDA in 2014. But like other prescription weight-loss drugs launched around that time – including Vivus Pharmaceuticals’ Qysmia and Arena Pharmaceuticals’ Belviq – sales fell well short of the billion-dollar expectations.

And three years later, doctors still aren’t writing scripts.

One of the primary issues is that most were trained in an era when obesity wasn’t considered a disease, Narachi noted in his La Jolla, California office overlooking the Pacific. It wasn’t until 2013 that the American Medical Association (AMA) controversially changed its stance.

“The AMA had a – I won’t call it a fight – but it was a gnashing of the teeth when they made that decision,” he said.

The association wanted to mobilize the healthcare community towards treating obesity, not just the secondary effects such as heart disease and type 2 diabetes. The symbolic fight was won, but real change has been slow.

Ania Jastreboff, M.D., Ph.D., an assistant professor of adult and pediatric endocrinology at Yale School of Medicine, is one of the few dedicated obesity specialists practicing in the United States. Via phone, Jastreboff said a significant amount education and training is still needed.

“Because obesity wasn’t recognized as a disease in and of itself, and many people still don’t recognize it as a chronic disease, it wasn’t being treated as such and it wasn’t being taught in medical school,” she said. “Nutrition would be allotted perhaps a day or two — if that — and physical activity, even less.”

It didn’t help that certain drugs like sibutramine and rimonabant had adverse effects and were withdrawn. Who wants to be an early-adopter when so many prior drugs have been pulled for dangerous side effects after several years on the market?

“In the past, anti-obesity medications have had a bit of a sordid history in terms of negative side effects or even negative medical consequences, including cardiovascular events, stroke, depression, and suicidal ideations,” Jastreboff explained.

They’re also tricky to master, she said. Not every drug works for every patient and the field has not advanced enough to be able to predict which medications are likely to benefit a specific patient. As a result, a lot of trial and error may be needed to get the right therapy and dose.

Even with the best-of-intentions, doctors are extremely busy. There’s never going to be a good time to open the Pandora’s box that is overweight and obesity in a five-minute appointment about something unrelated.

“There will be specialists that are really, really good or that lead the charge with the most innovative ways of doing it, but then that needs to get translated rapidly down to something that’s scalable for primary care,” Narachi said.

In the meantime, the vast majority of primary care physicians stick to a prescription for diet and exercise for the enormous number of patients struggling with their weight.

Despite these barriers, both Narachi and Jastreboff are optimistic that the field is moving in that direction.

“There needs to be more comprehensive education and it needs to come earlier on in medical training,” she said. “And it can’t just be ‘here’s a new medicine.’ There needs to be more depth to it. Which is what physicians want; they want evidence-based medicine.” 

Insurers won’t cover them
Knowledge is one thing. Practice is another.

“One of our biggest barriers, and there are many, is insurance coverage,”  Jastreboff declared. “If you try and prescribe a medication and it’s not covered by insurance, and the out-of-pocket cost is prohibitive, why would you try to prescribe it again?”

It’s difficult to build trust and confidence in a drug when you’re not able to freely use it to treat patients, she said.

Orexigen is also a victim of this problem, at least in the U.S. Unlike public health systems that are motivated to tackle the obesity problem early, U.S. insurers don’t cover the same patient long-term, Narachi said. 

“Private insurance is getting a free ride; they’re not paying much,” he said. “Only 22 percent of our scripts are from patients that are accessing coverage. If that was higher, then fewer costs would be shifted to Medicare later.”

Jastreboff agrees.

“I think it’s definitely short-sighted in terms of a public health point of view,” she said.

And Medicare cannot claim innocence either.

“Astonishingly, Medicare Part D is precluded from paying for weight loss drugs; won’t cover, cannot cover by statute,” Narachi marveled. “Even the government-controlled healthcare is precluded, it’s in the law, it’s in Part D.”

Medicare will pay for the downstream effects of obesity, but it can’t bring itself to recognize it as a disease just yet.

Patients aren’t asking for them
If primary care doctors are hesitant to bring up weight-loss medications, patients are similarly reserved. Many are not convinced about the efficacy of these drugs. And they are modest, steady benefits — not a ticket to overnight success.

“A patient may want to lose say 50 pounds, which for a person weighing 200 pounds would be 25 percent of their body weight,” Jastreboff said. “And that individual may think, ‘well, what is the potential weight loss with this medication? It’s 5 to 10 percent, right?’”

She stresses to patients that they may lose more or less, that’s the average response. Importantly, even 5 to 10 percent weight loss confers significant health benefits. If, as a result of the weight-loss drug, the patient can decrease or go off another medication for diabetes or hypertension, that’s meaningful, she said.

For patients, the messaging and the education is crucial.

Orexigen pivots
Orexigen, which hasn’t yet seen the pay off through higher sales of the drug, is making a renewed education and marketing push.

As of March 2016, the company regained full distribution rights to Contrave, following the dissolution of Takeda’s earlier licensing agreement. Thomas Cannell, Orexigen’s COO and president of global commercial products, is in charge of the revival.

“None of the weight-loss products were realizing the potential that people expected in 2010,” Cannell said in an interview at the company’s headquarters. “In 2010, everyone thought these were billion-dollar products. Everyone could see the huge unmet need… I think they overestimated doctors’ willingness to prescribe these new medicines.”

Now, a new plan has been formulated, centered around a fresh approach to the education of doctors and patients. “Doctors need to do something different than telling patients, ‘you need to have more willpower,’ or ‘you aren’t taking this seriously enough,’” Cannel explained. “That doesn’t help the patients. That just derails them in very predictable ways.”

Jastreboff agrees.

“A significant amount of weight bias remains,” she said. “There are still many who believe that obesity is the result of gluttony and sloth, which it absolutely is not. There are biological reasons for obesity and for what we do and why we do it.”

Orexigen’s new messaging approach works to relieve some of that guilt. The focus is on the biological mechanisms that underpin both the condition and the company’s therapeutic solution, a synergistic combination of bupropion (Wellbutrin) and naltrexone. It’s designed to help patients control the urge to overeat, increasing satiety over an extended period of time. The company is also using new telemedicine tools to improve patient engagement.

Jastreboff notes that drugs like Contrave can help patients make better food choices, while also preventing them from regaining the weight. It’s not a miracle pill, but it can help patients stay on track after years of unsuccessful attempts.

Future gains
In the months following Contrave’s approval in 2014, Orexigen’s shares reached $81 apiece. They now hover under $5. Arena has gone from $11 to just over $1 per share. Vivus is also trading around the $1 mark, after a 2012 high of $28.54.

Other drugs have joined the market, some via the treatment of Type 2 diabetes, which seems to be an easier indication to break into — and to get coverage for.

Medical device treatments are in development and on the market, including the controversial AspireAssist, which empties the contents of the patient’s stomach after each meal. Carlsbad, California-based Obalon Therapeutics gained FDA approval in 2016 for its gastric balloon, designed to trigger a feeling of fullness. ReShape Medical and Allurion Technologies have taken a similar approach.

Meanwhile, Jastreboff is independently traveling the country training other physician’s and caring for patients in her care with overweight and obesity. Last year she coauthored the obesity medicine treatment guidelines for the comprehensive care of patients with obesity for the American Association of Clinical Endocrinologists.

“I would say there is definitely progress,” she said. “And I would say since four new medications were FDA approved in 2012 and 2014, there has definitely been more of a shift because obviously, as physicians, we want to help patients. And if we don’t have tools to help them, we feel powerless to do so.”

Photo: VladimirFLoyd, Getty Images