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Thursday, October 13, 2022

New Generation of Weight Loss Medications Offer Promise — But at a Price

 Excitement is building about a new generation of drugs that tout the ability to help adults with excess weight shed more pounds than older drugs on the market.

Some patients, obesity medicine specialists say, are experiencing decreases in blood pressure, better-managed diabetes, less joint pain, and better sleep from these newfound treatments.

The newer drugs, which are repurposed diabetes drugs, "are showing weight loss unlike any other medications we've had in the past," said David Creel, a psychologist and registered dietitian in the Bariatric & Metabolic Institute at the Cleveland Clinic.

Yet for him and other experts, the thrill is tempered.

That's because no single drug is a magic solution by itself, and it's possible many patients will need to take the drugs long term to maintain results. On top of that, the newest treatments are often very costly and often not covered by insurance.

The five-figure annual costs of the new medications are also raising concern about access for patients and what widespread use could mean for the nation's overall health care tab.

Evaluating the trade-offs — weighing the value of better health and possibly fewer complications of obesity down the road against the upfront drug costs — will increasingly come into play as insurers, employers, government programs, and others who pay health care bills consider which treatments to cover.

"If you pay too much for a drug, everyone's health insurance goes up. Then people drop off health insurance because they can't afford it," so providing the drug might cause more harm to the system than not, said Dr. David Rind, chief medical officer for the Institute for Clinical and Economic Review, or ICER, a nonprofit group that reviews medical evidence to evaluate treatments for effectiveness and cost.

Many commercial insurers currently limit coverage to only some of the drugs currently available, or require patients to meet certain thresholds for coverage — often pegging it to a controversial measure called "body mass index," a ratio of height to weight. Medicare specifically bars coverage for obesity medications or drugs for "anorexia, weight loss or weight gain," although it pays for bariatric surgery. Coverage in other government programs varies. Legislation that would allow medication coverage in Medicare — the Treat and Reduce Obesity Act — has not made progress despite being reintroduced every congressional session since 2012.

As insurers view the cost of treatments with concern, manufacturers see a potential financial bonanza. Morgan Stanley analysts recently said "obesity is the new hypertension" and predicted industry revenue from U.S. obesity drug sales could rise from its current $1.6 billion to $31.5 billion by 2030.

It's easy to see how they could predict that startling number based simply on potential demand. In the U.S., 42% of adults are considered obese, up from 33% a decade earlier. Health problems sometimes linked to weight, such as diabetes and joint problems, are also on the rise.

Even losing 5% of body weight can provide health benefits, say experts. Some of the new drugs, which can help curb hunger, aid some patients in surpassing that marker.

Wegovy, which is a higher dose of the self-injectable diabetes drug Ozempic, helped patients lose an average of 15% of their body weight over 68 weeks during the clinical trial that led to its FDA approval last year. After stopping the drug, many patients followed in an extension of the trial gained back weight, which is not uncommon with almost any diet medication. Wegovy has spent much of the year in short supply due to manufacturing issues. It can cost around $1,300 a month.

Another injectable drug, still in final clinical trials but fast-tracked for approval by the FDA, could spur even greater weight loss, in the 20% range, according to Eli Lilly, its manufacturer. Both drugs mimic a hormone called glucagon-like peptide 1, which can signal the brain in ways that make people feel fuller.

The average weight loss from both, however, puts the drugs within striking distance of results seen following surgical procedures, offering another option for patients and physicians.

But will the range of old and new prescription medical products — with even more in the development pipeline — be the answer to America's weight problem?

A big maybe, say experts. For one thing, the medications and devices don't work for everyone and vary in effectiveness.

Plenity is a prime example. With a price tag of $98 a month, it's considered by the FDA to be a device and requires a prescription. During clinical trials, about 40% of people who tried it failed to lose weight. But among the other 60%, the average weight loss was 6.4% of body weight over 24 weeks when coupled with diet and exercise.

That average puts it in line with other, older, prescription weight loss medications, which often show a 5% to 10% weight loss when taken over a year.

While it is true that weight loss drugs — both old- and new-generation — don't work for everyone, there's enough variation among individuals that "even the older drugs work really well for some people," said Rind at ICER.

But it's too soon — especially for the newer drugs — to know how long the results can last and what patients will weigh five or 10 years out, he said.

Still, advocates argue that insurers should cover treatments for weight issues as they cover those for cancer or chronic conditions like high blood pressure. Paying for such treatment could be good both for the patient and insurers' bottom lines, they argue. Over time, insurers may pay less for people who lose weight and then avoid other health complications, but such financial gains to the health system could take years or even decades to accrue.

Financial benefits for drugmakers are mixed so far. Novo Nordisk, the maker of Wegovy and Ozempic, saw obesity care sales grow 110% in the first half of the year, driven by Wegovy, but its stock price remained flat and even dipped in September. But Lilly, which won approval for a new diabetes drug, Mounjaro, that may soon also get the green light for weight loss, saw its September stock prices 34% higher than last September's.

Some employers and insurers who pay health care bills are also asking whether the drugs are priced fairly.

ICER recently took a look, comparing four weight loss medications. Two, Wegovy and Saxenda, are new-generation treatments, both made by Novo based on an existing injection diabetes drug. The other two — phentermine/topiramate, sold by Vivus as Qsymia, and bupropion/naltrexone, sold as Contrave by Currax Pharmaceuticals — are older therapies based on pill combinations.

Results were mixed, according to a report released in August, which will be finalized soon after public comments are evaluated and incorporated.

Wegovy showed greater weight loss compared with other treatments. But Qsymia also helped patients lose a substantial amount of weight, Rind said. That older drug combination has a net cost, after manufacturer discounts, of about $1,465 annually in the second year of use, compared with Wegovy, which had a net cost of $13,618 in that second year, the report said. Many patients may be prescribed weight loss drugs for years.

With such numbers, Wegovy did not meet the group's cost-effectiveness threshold.

"It's a great drug, but it's about twice as expensive as it should be" when its health benefits are weighed against its cost and potential to drive up overall medical spending and health premiums, said Rind.

Don't expect costs to go down anytime soon, though, even as other new drugs are poised to hit the market.

Lilly, for instance, has yet to reveal what Mounjaro will cost if it clears clinical trials for use as a weight loss medication. But a hint comes from its $974-a-month price as a diabetes treatment — an amount similar to that of rival diabetes drug Ozempic, Wegovy's precursor.

Novo charges more for Wegovy than Ozempic, although the weight loss version does include more of the active ingredient. It's possible Lilly will take a page out of that playbook and also charge more for its weight loss version of Mounjaro.

Dr. W. Timothy Garvey, a professor in the department of nutrition sciences at the University of Alabama-Birmingham, predicts insurance coverage will improve over time.

"It's undeniable now that you can achieve substantial weight loss if you stay on medications — and reduce the complications of obesity," Garvey said. "It will be hard for health insurers and payers to deny."

One thing the new focus on medication treatment may promote, most of the experts said, is to temper the bias and stigma that has long dogged patients who are overweight or have obesity.

"The group with the highest level of weight bias is physicians," said Dr. Fatima Stanford, an obesity medicine specialist and the equity director of the endocrine division at Massachusetts General Hospital. "Imagine how you feel if you have a physician who tells you your value is based on your weight."

Rind sees the new, more effective therapies as another way to help dispel the notion that patients "aren't trying hard enough."

"It's become more and more obvious over the years that obesity is a medical issue, not a lifestyle choice," Rind said. "We've been waiting for drugs like this for a very long time."

https://www.medscape.com/viewarticle/982397

How payers have exploited Medicare Advantage

 Though Medicare Advantage was designed to help lower federal healthcare expenditures, payers have exploited the program through elaborate schemes that make patients appear sicker than they actually are — thereby leading to higher payments from CMS, according to an Oct. 8 report from The New York Times.

The Times analyzed dozens of fraud lawsuits against major payers, inspector general audits and watchdog investigations to show how insurers have abused the program to raise their profits by billions.

  • Accused of fraud by a whistleblower: UnitedHealth Group, Humana, Kaiser Permanente, Cigna, SCAN Group

  • Accused of fraud by federal government: UnitedHealth Group, Elevance Health, Cigna, SCAN Group

  • OIG says it overbilled: UnitedHealth Group, Humana, CVS Health, Elevance Health, BCBS Michigan, Cigna, Highmark, SCAN Group

According to the report, Elevance Health paid physicians more if they had sicker patients, UnitedHealth Group directed employees to look through old medical records to find more illnesses and Kaiser Permanente urged physicians to add extra illnesses to medical records — those that found enough were rewarded with champagne or bonuses.

The report said payers used third-party companies to support the alleged fraud. At healthcare conferences, companies offered insurers an analysis of their medical claims and where additional codes could be added. Payers like Elevance, Molina and Cigna reportedly used in-home clinical teams to diagnose patients with additional illnesses. 

James Taylor, MD, was previously a coding expert with Kaiser Permanente and is now accusing the payer-provider of fraud. He told The Times he was instructed by superiors to find additional illnesses that would lead to expensive claims.

"The cash monster was insatiable," he said. "It was an actual agenda item and how could we get this."

"We are confident in our compliance with Medicare Advantage risk-adjustment program requirements," a Kaiser spokesperson told The Times. "Our policies and practices represent well-reasoned and good-faith interpretations of sometimes vague and incomplete guidance from CMS."

Total estimated overpayments to insurers from the federal government in 2020 ranged from $12 billion to $25 billion, according to The Times.

Elevance is currently facing a federal lawsuit for allegedly receiving more than $100 million in MA overpayments from 2014 to 2018.

According to the report, payers have largely denied the allegations and said they were attempting to accurately document all of their patients' conditions. AHIP also said there has been no purposeful inflation of diagnoses.

"Professionals can look at the same medical record in different ways," an AHIP spokesperson told The Times.

The Better Medicare Alliance, a national MA research and advocacy group, rebuked the report Oct. 9:

"The story cherry-picks allegations — in some cases more than a decade old — to paint an inaccurate and incomplete picture of a vital part of Medicare that is providing better and far more affordable health care for 30 million seniors," Mary Beth Donahue, president and CEO, said, "The story ignores basic facts, including that Medicare Advantage saves seniors nearly $2,000 per year — savings that are particularly important for seniors on fixed incomes in a period of inflation on household costs."

https://www.beckerspayer.com/payer/how-payers-have-exploited-medicare-advantage.html

Tiziana Plans IND for Intranasal Alzheimer's Treatment with Promising CNS History

 Tiziana Life Sciences plans to submit an Investigational New Drug Application for a Phase I trial studying intranasal formulab, a novel treatment option for Alzheimer’s Disease, the company announced Wednesday. 

Intranasal formulab, also known as anti-CD3, is unique among CNS-related treatment options because of the way it is administered and the way it reacts in the body by naturally inducing regulatory T cells. The treatment has already shown promise for patients with other CNS-related inflammatory diseases. 

Dr. Howard Weiner, co-director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital at Harvard Medical School, told BioSpace he believes an intranasal mechanism of action is a "very broad approach to treating neurological diseases." 

Two patients with secondary progressive multiple sclerosis (SPMS) previously showed clinical improvement with the drug as measured by the Expanded Disability Status Scale (EDSS) after being administered the treatment over a six-month period. 

With few treatment options available for patients specifically with SPMS, instransal foralumab presents a promising possibility for advancement against this CNS-related inflammatory disease. 

"What makes it different than other anti-CD3s that have been out there is the fact that it's fully human and it's delivered locally," said Dr. Matthew Davis, RPh, chief scientific officer and chief medical officer of Tiziana Life Sciences.  

He emphasized the treatment is "a very targeted, clean delivery system that allows the effect of the antibody to be seen in the body without needing the antibody itself to be throughout the body." 

A Potential Three-in-One Treatment

Though the symptoms of SPMS and Alzheimer's disease (AD) are notably different, Tiziana believes formulab will still show improvement in AD. 

The treatment works by dampening microglial activation in the brain, which is a hallmark mechanism of CNS-related diseases. This inflammation in the brain is what drives diseases like AD, ALS and SPMS. 

The two SPMS patients treated showed decreased microglial inflammation, as did the animal models for MS and AD.

While MS patients don't have problems with cognition in the same way as AD patients, they do face problems with walking and physical function. Weiner believes administering this treatment in humans will reduce cognition issues in AD patients, similarly to how it reduced physical symptoms in SPMS patients and animal models. 

Weiner said he believes the success of this treatment may spark other treatments with a similar mechanism of action. 

Davis, who works on drug development, said the phrase "kill early, kill often" applies to the way this treatment is being studied. If the targeted microglial activation did not show an effect from the treatment, the trial would not proceed.

As the treatment moves forward in AD, Weiner noted the drug could also treat ALS, another CNS-related disease. 

Because the mucosal immune system involves the gut, respiratory and nasal cavities, the body has a natural anatomy to interface with the environment. Intranasal treatment "stimulates the immune system in a natural way," he said. 

This delivery method has aided in safety testing.  

The company has "seen no safety signals at all in animals" that have been tested and no significant side effects have been recorded in the human trials for MS, Davis said.

Despite the T-regulator cells circulating, there have been no systemic effects recorded, which leads Tiziana to believe "the safety profile should be superior to a non-nasally delivered antibody." 

Tiziana plans to file the IND by the third quarter of 2023 and start the Phase I program at the end of 2023. The company previously received an affirmative written response from the FDA for its pre-Investigational New Drug Application.

https://www.biospace.com/article/tiziana-to-submit-ind-for-alzhemier-s-treatment-that-shows-promise-in-ms-spms/

UnitedHealth Earnings On Deck, With Dow Jones Giant Near Key Support

 UnitedHealth earnings loom Friday morning, kicking off third-quarter results for health insurers with future Medicare Advantage payments also in focus. UNH stock fell Thursday morning after consolidating over the past several weeks.

Molina Healthcare (MOH), Humana (HUM) and Cigna (CI) have been leading the market, trading right around consolidation buy points as investors pour into defense growth names. But Centene (CNC) has come under strain, while CVS Health (CVS) has tumbled, in large part due to its Aetna insurance unit.

UnitedHealth (UNH) is in between. UNH stock has pulled back since Aug. 19 and is trying to hold long-term support. But its relative strength line is right at highs, marked by a blue dot at the end of that line on the weekly MarketSmith chart.

Year to date through Oct. 11, UNH stock carries a 0.5% gain vs. a 24.7% decline for the total U.S. stock market and 18.4% drop for the Dow Jones Industrial Average as a whole.

UnitedHealth Earnings

Estimates: Analysts polled by FactSet expect UnitedHealth earnings to rise 20% vs. a year earlier to $5.43 per share. Revenue is seen climbing 11% to $80.573 billion. That would mark the second straight quarter of faster EPS growth but the second quarter of slightly slowing revenue gains.

Results: Check back early Friday.

Outlook: Analysts forecast UnitedHealth earnings per share to rise 15% to $21.87 in all of 2022. That's near the high end of the health insurance giant's raised full-year EPS guidance of $21.40-$21.90.

UNH Stock

Shares of UnitedHealth fell 1.5% to 492.69 amid a broad decline on the stock market today, falling further below the 200-day moving average. UNH stock has formed a flat base with a 553.23 buy point, but remains well below the entry for now. It's also below the 50-day line.

A strong move above the 50-day line could offer an early entry, depending on market conditions.

That flat base is within a larger consolidation going back six months.

Even though UNH stock has drifted lower, the RS line is right at record highs. That is a sign of outperformance vs. the S&P 500.

Centene, Cigna, Molina and Humana also fell Thursday morning, along with Aetna-owner CVS.

Optum Health, Medicare In Spotlight

When UnitedHealth reports Thursday, its Optum Health subsidiary will be in focus.

The fast-growing Optum unit has become a key driver of UnitedHealth earnings. The service has benefited from the expansion of value-based care initiatives, and further growth in revenue per consumer would be a positive sign.

But on Sept. 5, UnitedHealth and Amazon (AMZN) lost their reported bids to acquire home care tech platform Signify Health. Instead, CVS Health purchased Signify Health (SGFY) in a deal valued at $8 billion.

UnitedHealth's Optum offers similar aging-in-place services, via the purchase of Landmark Health in 2021. It also announced the purchase of home health provider LHC Group in April.

At-home services are key for Medicare members.

For health insurers, the Medicare business itself is favorably poised for growth, with the U.S. set to boost Medicare Advantage payments by 8.5% in 2023.

However, UnitedHealth, along with Centene and CVS' Aetna, will lose Medicare Advantage bonus payments due to lower performance ratings. That news hit all three stocks last Friday.

Investors in UNH stock will look for continued growth in Medicare and Medicaid membership.

They will also watch UnitedHealth's medical cost ratio. Analysts expect it to decline 0.8% to 82.4%.

The metric measures benefits paid as a share of premiums, so lower is better for the company.

https://www.investors.com/news/unh-stock-unitedhealth-earnings-q3-2022/

Biogen upped to Buy from Hold by Stifel

 Target to $299 from $223

https://finviz.com/quote.ashx?t=BIIB&ty=c&ta=1&p=d

Celyad discontinues development of colorectal cancer candidate

 CYAD-101 – Allogeneic TIM-based, NKG2D CAR T Candidate for Metastatic Colorectal Cancer (mCRC)

  • Based on a strategic, financial and medical review, taking into account the costs associated with the pursuit of the program and the delays to reach key medical milestones following the resolution of the previous Clinical Hold, the Company has decided to discontinue the development of CYAD-101

  • There were no new safety concerns leading to this decision

  • All patients currently on CYAD-101 trials will continue to receive their protocol-defined follow-up

CYAD-211 – Allogeneic shRNA-based, anti-BCMA CAR T candidate for relapsed or refractory multiple myeloma (r/r MM)

  • Celyad Oncology continues to evaluate CYAD-211 in the IMMUNICY-1 Phase 1 trial which was developed to validate shRNA technology in the clinic. Data have shown safe use of shRNA to date, and its use as a technology to control Graft-versus-Host disease of allogeneic CAR Ts appears to be a viable approach

  • Clinical updates are expected by year end

Inovio: Early Data From Experimental Drug For Respiratory Tract Disease

 

  • Inovio Pharmaceuticals Inc  announced interim results from an ongoing Phase 1/2 trial evaluating INO-3107 for HPV 6 and HPV 11-associated Recurrent Respiratory Papillomatosis (RRP) in adults. 
  • RRP is caused primarily by HPV types 6 and/or 11 characterized by the development of small, wart-like growths, or papillomas, in the respiratory tract. 
  • In the first cohort of 21 participants, INO-3107 showed a statistically significant improvement in the clinical endpoint of the number of surgical interventions needed to control papilloma growth. 
  • INO-3107 was also observed to be well-tolerated and immunogenic in the trial. 
  • In the trial, treatment with INO-3107 induced cellular responses against both HPV 6 and HPV 11, inducing CD4 and CD8 T cells. All 21 participants demonstrated an increase in peripheral T cells to one or more antigens in INO-3107 post-baseline. 
  • T-cell responses against HPV 6 and HPV 11 were also still observed at Week 52, 43 weeks after treatment with INO-3107, indicating a persistent cellular memory response.
  • INO-3107 was well-tolerated, with all participants completing the trial follow-up. 
  • Results from the second cohort of 11 patients are expected in the first half of 2023.