Rx Pulse Newsletter

What is Ozempic, and Why is it Getting so Much Attention?

With endorsements from celebrities and other high-profile users, the injectable semaglutide (Ozempic) for weight loss is increasingly popular and contributing to a nationwide shortage of the diabetes drug. Ozempic received FDA approval in 2017, and its weekly doses lower blood glucose levels, regulate insulin and reduce cardiovascular risks in people with diabetes. As a result, heavier-weight patients experience weight loss because the medication makes users feel fuller faster and slows the process of emptying the stomach. Taking note of the results, the manufacturer applied for and received FDA clearance last year for their product, Wegovy, which employs a higher dose of semaglutide than Ozempic and is primarily intended to treat obesity.

On TikTok, the hashtag #Ozempic currently has over 273 million views. With demand taking off and supply unable to keep up, patients who are unable to get Wegovy are snapping up supplies of Ozempic through off-label prescribing or purchases made through online channels. In addition to reducing the availability of Ozempic for the intended demographic, using Ozempic could be dangerous for people who want to lose weight quickly but do not meet the criteria for obesity.

“Semaglutide has not been systematically studied in people with normal body weight,” explained Dr. Hwang, who speculates that these individuals might experience more intense adverse effects such as nausea, fatigue, dehydration, diarrhea, and/or constipation. Pharmacy benefit managers (PBMs) are working on adding utilization management to ensure Ozempic is used appropriately for diabetes and not off-label. OptumRx released their update to require prior authorization beginning in 2023, with CVS to follow with their approval criteria sometime in Q1 2023.

Patients Complain Some Obesity Care Startups Offer Medication, and not Much Else

As more Americans seek to lose weight, many are turning to the latest fad, fitness craze or herbal supplement. Now several telemedicine startups are providing consumers with access to a class of drugs known as GLP-1 agonists (Ozempic, Trulicity, Rybelsus, Victoza), which are effective at triggering weight loss, combined with intensive behavioral coaching online. One startup, Calibrate Health, said it has already served about 20,000 patients, while a startup called Found said it has served 135,000 patients since July 2020, according to CEO Sarah Jones Simmer. Calibrate Health costs patients nearly $1,600 annually, not including the price of drugs that can cost about $1,500 per month without insurance. Patients say insurers reimburse the cost of GLP-1 agonists only in certain situations. A spokesperson for Found says the company offers a 6-month plan for nearly $600 inclusive of generic drugs but not newer GLP-1 agonists. Together, Found and Calibrate Health have raised more than $200 million in combined venture funding, according to Crunchbase.

Scott Butsch, director of obesity medicine at the Cleveland Clinic, said these startups are convenient and may reduce the effect of stigma. However, he adds, “I think programs that do not have a multidisciplinary team are less comprehensive and, in the long term, less effective.” Meanwhile, some patients say the startups are not very responsive, and some say they cannot get the newest medications. One Found patient said she was prescribed Zonisamide, a generic anticonvulsant that has helped some people lose weight; however, it caused her to be “up all night, and [her] thoughts were racing” and she developed sores in her mouth. It took a week to change her prescription and have the new medication arrive at her home, and in the meantime, she went to an urgent care clinic to have the mouth sores examined.

The Threat of Synthetic Opioids

Over the last three years, much of the news has been focused on COVID-19. While the spotlight may have been elsewhere, the opioid crisis in the US continued. The COVID-19 pandemic brought with it social isolation, disruption of treatment and recovery programs, and increased social and economic pressure, all contributing to a record-breaking number of opioid overdose-related deaths in the US in 2021.

In addition to COVID-19-related factors, the crisis has also been largely driven by the increased availability of synthetic opioids. In 2020, 82% of all opioid-involved deaths were caused by synthetic opioids, including Fentanyl. Specifically, Fentanyl remains the deadliest drug threat facing the nation, according to the US Drug Enforcement Administration, which found that in 2022, six out of ten Fentanyl-laced counterfeit prescription pills contained a potentially lethal dose, compared to four out of ten in 2021.

Increased Legislative and Treatment Action

While the country faces an uphill battle regarding the opioid crisis, there have been recent legislative and treatment-related updates to make note of, as their impact may be significant. Legislatively there has been a shift in who is being held, at least partially, responsible for the crisis.

In November 2022, CVS Health and Walgreens both agreed to pay more than $10 billion to resolve opioid-crisis lawsuits made by various state governments and Native American tribes. The suits blamed the country’s two largest pharmacy chains for playing a significant role in driving the opioid epidemic. This most recent settlement is not the first time either company has faced legal action surrounding opioids.

In March 2022, CVS and Walgreens both agreed to pay millions of dollars to settle suits against them in Florida and New York, and in August 2022, both companies, along with Walmart Inc., were ordered by an Ohio federal judge to pay a combined $650 million in damages to two Ohio counties for their role in the crisis. That ruling was the first of its kind and has set a precedent for other states and local governments to follow. The increase in legislative action, along with increased pressure from federal agencies, has led many retail pharmacies, including CVS and Walgreens, to change their opioid-related policies in the hopes of limiting the spread of opioids into the community.

Access to treatment for opioid-related overdose has also been a topic of interest in recent years. Naloxone is a medication designed to treat opioid overdose, and as of 2022, it is now available without prescription in all 50 states. While each state may differ in its specific laws surrounding access to Naloxone, this increase in availability is a huge win overall. In addition to decreased restrictions on Naloxone from the pharmacy, the FDA is now considering approving a nonprescription, over-the-counter (OTC) option.

In December 2022, a startup called Pocket Naloxone Corporation submitted its results from a small, randomized trial of its OTC Naloxone nasal swab. The company plans to apply for new drug approval in early 2023. The FDA has encouraged drug manufacturers to apply for approval for OTC versions of Naloxone as the agency is committed to making Naloxone as affordable and easily available as possible.

Fighting the opioid crisis will continue to require a multi-faceted approach, with the pharmaceutical and legislative industries being a part of the bigger picture.

Pharma Companies Boost Drug Prices to Start Year

Pharmaceutical companies began the new year, as anticipated, raising the sticker prices on hundreds of prescription medicines.

January is historically the biggest month for drugmakers to raise prices. Drugmakers including Pfizer, GlaxoSmithKline, Bristol Myers Squibb, AstraZeneca and Sanofi were predicted to raise prices in the US on more than 350 unique drugs in early January, according to data analysts from healthcare research firm 3 Axis Advisors.

On average, drugmakers have appeared to hike list prices by 5%, according to industry analysts. That figure is in line with increases taken in the past four years but below the national consumer inflation rate in 2022.

The increases are expected as the pharmaceutical industry prepares for the Biden Administration’s Inflation Reduction Act (IRA), which allows the government’s Medicare health program to negotiate prices directly for some drugs starting in 2026. The industry is also contending with inflation and supply chain constraints that have led to higher manufacturing costs.

Antonio Ciaccia, president of 3 Axis, stated “Drugmakers have focused on launching their drugs at higher prices because of the attention paid to annual price increases. The IRA should further this dynamic.”

Historically, price increases have been the primary tool drugmakers have used to boost sales, Elliot Wilbur, an analyst at Raymond James, noted. But in 2022, volume accounted for more growth in branded drug sales rather than price adjustments.

Drug-Price Hikes Unsupported by New Clinical Evidence

The Institute for Clinical and Economic Review (ICER) recently published its latest report on unsupported price increases (UPI) of prescription drugs in the United States. Among the top 10 drugs with net price increases in 2021 that had substantial effects on US spending, ICER determined that seven lacked adequate new evidence to support any price increase. These increases accounted for $805 million in additional costs over one year.

“Increases in drug prices frequently occur without important new evidence,” said David Rind, MD, ICER’s chief medical officer. “There remain many high-cost brand drugs that continue to experience significant annual price hikes, even after accounting for their rebates. List prices also continue to increase, which can present real hardships to patients who must pay deductibles or coinsurance.”

Employer Health Costs on the Rise

Employer health costs could increase by 6.5% in 2023, according to a new analysis from Aon. The researchers found that average costs per employee will reach $13,500 in 2023. This is more than double the 3% increase that employers saw in 2022 but far below the current inflation index, according to Aon. The factors driving these increases include economic inflation, new technology, blockbuster drugs, specialty drugs and severe catastrophic claims.

Most working-age Americans get health insurance through their employer, but even they are finding it tougher to afford medical care these days, a new study shows. There are some likely explanations, including rising healthcare costs and moves by insurance plans to impose greater payment responsibility onto their consumers. Approximately 61% of Americans younger than 65 get health insurance through their employer, and businesses use that benefit to help attract workers. Researchers found that over the past 20 years, a growing number of Americans with job-based health insurance have been skipping medical care due to costs.

The Commonwealth Fund Biennial Health Insurance Survey describes the state of Americans’ health insurance coverage in 2022 by assessing the extent and quality of coverage for US working-age adults.

The survey highlights:

• 43% of working-age adults were inadequately insured in 2022. These individuals were uninsured (9%), had a gap in coverage over the past year (11%), or were insured all year but were underinsured, meaning that their coverage didn’t provide them with affordable access to healthcare (23%).
• 29% of people with employer coverage and 44% of those with coverage purchased through the individual market and marketplaces were underinsured.
• 46% of respondents said they had skipped or delayed care because of the cost, and 42% said they had problems paying medical bills or were paying off medical debt.
• Half (49%) said they would be unable to pay for an unexpected $1,000 medical bill within 30 days, including 68% of adults with low income, 69% of Black adults and 63% of Latinx/Hispanic adults.
• 68% of Democrats, 55% of Independents and 46% of Republicans said President Biden and Congress should make healthcare costs a top priority in the coming year.

Sara Collins, vice president of healthcare coverage and access at the nonprofit Commonwealth Fund, and her colleagues found that 29% of Americans with employer-sponsored health coverage were “underinsured,” according to the study. That meant their out-of-pocket costs for healthcare in the past year were at least 10% of their household income (or 5% for people living under the poverty line), or their health plan’s deductible was at least 5% of their household income. Collins revealed, “The root of the problem is the ever-growing cost of healthcare services which has far outpaced income growth, yet ultimately gets passed down to consumers.”

Sources: Amy Norton. “It’s Getting Tougher to Afford Health Care, Even with Employer-Sponsored Insurance,” US News, 2021.
Sara Collins, Lauren Haynes, Relebohile Masitha. “State of U.S. Health Insurance in 2022: Biennial Survey,” The Commonwealth Fund, 2021.

Low Stock and Limited Approvals

There were several drug updates over the past few months ranging from drug shortages to decreased FDA approvals.

First, there is an Adderall shortage that was announced in late 2022. The 10-milligram doses have recovered already, but the higher doses are not expected to recover until around March 2023. Shortages are the direct result of a labor shortage at Teva, which has caused production delays that have started to appear at other companies. Additionally, there has been an uptick in the number of ADHD diagnoses over the past few years adding to the issue. Many people currently have to go without therapy and are nervously awaiting a resolution.¹

While not in shortage, Nestlé is looking to drop their peanut allergy treatment, Palforzia, as sales have not lived up to expectations. This move comes two years after Nestlé bought the developer of the medication in a $2.6 billion deal. “What was once thought as a blockbuster medication has turned into more of a niche therapy,” says Mark Schneider, CEO of Nestlé. The therapy works by reducing the severity and frequency of allergic reactions to peanuts. Clinical trials showed that two-thirds of participants could tolerate up to 600 milligrams of peanut protein (roughly two peanuts) compared to only 4% of participants treated with a placebo. Schneider said sales have been modest, likely because of the cumbersome treatment schedule in which the patient must visit their allergist every two weeks for 4-5 months and remain for at least one hour for each visit under medical supervision.²

Moving into drug approval news, Tzield was recently approved in November 2022. Tzield is approved for delaying stage 3 type 1 diabetes in children eight and older. Type 1 diabetes is a disease where the patient’s immune system attacks and destroys cells that produce insulin in the body. This leads to increased glucose in the body which requires insulin shots (or pumps) and constant checking of blood glucose throughout the day. Tzield works by binding to certain immune system cells and delaying the destruction of insulin-producing cells, which slows progression to stage 3 type 1 diabetes. This medication is given through IV infusions once biweekly. In phase 3 studies, Tzield was shown to delay stage 3 onset for 50 months compared to 25 months in those patients who received a placebo. The most common side effects were decreased levels of white blood cells, rash and headaches.³

Despite the approval of Tzield, drug approvals have decreased in 2022 from an average of 51 new drug approvals per year since 2017 versus only 37 drugs approved in 2022. This decrease may be related to the issues that surrounded the FDA’s controversial approval of Aduhelm in 2021. Through the first half of 2022, there were only 19 green-lighted drugs, including a two-month period where no drugs were endorsed, and 14 control response letters, for a 57.6% approval rate compared to 2021’s approval rating of 66.7%. There would have been even fewer approvals for 2022 if it wasn’t for a late rush of five approvals seven days before Christmas. As for the winners of approvals for 2022, Bristol Myers Squibb floated to the top registering three more approvals than every other company.

Some of the other impactful approvals are listed below:

• Eli Lilly’s nod for Mounjaro could be a game changer for diabetes and obesity patients, not to mention the windfall it could produce for the company as it squares off against Novo Nordisk’s Ozempic and Wegovy.
• Alnylam won a key approval for Amvuttra, a gene silencer to treat hereditary ATTR amyloidosis. The drug is expected to become a blockbuster quickly, with sales of $1.7 billion projected by 2026.
• Also expected to be in the sudden-blockbuster orbit is Johnson & Johnson and Legend’s multiple myeloma drug Carvykti.⁴

Upcoming Influx of Humira Biosimilars

The launch of Humira biosimilars is expected to end the most profitable monopoly in the history of the pharmaceutical industry. For years AbbVie has produced Humira, the world’s top selling drug. This injectable, approved for an array of inflammatory diseases, has earned nearly $200 billion from sales.

Many are wondering which drugs will secure a position on formularies and when this will occur. Currently, two of the three top PBMs have made that decision. OptumRx was the first to announce their decision to keep Humira on their formulary but will also add three competing biosimilars. Express Scripts later announced they would follow suit by allowing both biosimilars and Humira to land on their formulary. Humira is a preferred medication for the majority of covered American lives, according to data from MMIT Analytics. They also reported that over 50% of payers reported that they would likely make changes in their Humira contracting within the year. However, one-third of payers declared their reluctance to make premature contracting changes despite pricing reductions.

Humira losing its dominant status will likely take several years and will not be an instant shift. Although AbbVie will now face competition from biosimilars, it has built a strong market for Humira. The consensus for most payers is that they will likely offer more open coverage throughout 2023. This will allow for more biosimilars to become available before making final contracting and coverage decisions. As for many other payers, they stated they will likely not make any changes to their formulary until 2024 or 2025.

When deciding which available Humira biosimilars will be on the formulary, the cost is not the only payer consideration. Biosimilars with designated interchangeability will likely have a slight advantage over others. Interchangeability status allows pharmacists to choose a biosimilar over Humira when filling prescriptions and will not require contact with the prescribing doctor for substitution. Another influence that will be considered is the formulation of the biosimilar.

In July 2018, AbbVie launched a higher concentration, citrate-free Humira, which is now the preferred formulation most physicians prescribe. This preparation causes less discomfort when injected and has a thinner needle. Most biosimilars coming to market do not have these desired attributes, therefore making it even harder for them to make a splash in the marketplace. Of all the Humira products currently approved, Hadlima is the only one with a high concentration and will be citrate-free when launched. Approval for Hadlima’s interchangeability status is expected post-launch.

For years, biosimilars have failed to make a significant impact on lowering the costs of some of the best-selling prescription drugs in the US. For the pharmaceutical industry, the launch of Humira biosimilars is a major moment. Their arrival is the biggest test case yet regarding whether biosimilars can save the healthcare system significant amounts of money. So far, the biosimilars currently available for other popular medications have not lived up to previously high expectations of their impact. More companies are anxious to watch how this plays out as several drugs, such as Enbrel and Stelara, will also lose their patent protection in the coming years.

Cell and Gene Therapies

Within the umbrella of gene therapy, there are at least two, more specific categories — cell and gene therapy. Both therapies are potentially curative since they target the cause of a condition, but they function in slightly different ways.

Gene therapies replace or repair and stimulate or add a missing or damaged gene into a patient’s cells. The currently available gene therapies are indicated for rare genetic conditions affecting only a small percentage of the population. In most cases, they are given to the patient once in a lifetime. These therapies carry a hefty price tag and may also have other associated costs such as hospital stays, lab work, monitoring and other infusion-related costs.

Gene Therapy Cost Chart

With most cell therapies, either a donor’s or a patient’s own cells are removed, modified to reproduce or repair specific cells or may be used to transport treatment within the body. Once the cells are modified, they are then reintroduced back into the patient, often via infusion. A growing area for cell therapy development is oncology, with products like CAR-T cell therapies that modify immune cells to target several types of cancer.

Cell Therapy Cost Chart

The most recent product approval occurred on December 16, 2022, for Adstiladrin. Adstiladrin treats non-muscle-invasive bladder cancer (NMIBC) that is resistant to other therapy options. It works by introducing a gene into the cells of the bladder wall that enhances the cells’ ability to fight off cancer. Adstiladrin is administered once every three months for up to 12 months. Adstiladrin is expected to be available in the US in the second half of 2023.

Bladder cancer is the sixth most common type of cancer in the US. The CDC estimates that 75,000 people are diagnosed with bladder cancer annually, and 16,700 die from bladder cancer each year in the US. In addition, 75%-90% of bladder cancers are classified as NMIBC and have a rate of recurrence between 30%-80%. Bladder removal surgery was one of the few options for these patients prior to this approval.

These gene and cell therapy-related products are relatively new to the healthcare industry, and determining how to make their higher-than-average costs affordable, especially in the complex US market, is a point still being worked on. Some of the concerns being discussed in the industry about cell and gene therapies are:

• Affordability. Each new product seems to come with a higher price tag, and at this high level, any of these expenses could be out of range for an employer. Current payment models may not support equal access.
• Member coverage. If a member leaves an employer after receiving therapy, the plan that paid for the one-time treatment may not be able to realize the long-term benefits. Member changing insurance plans can also impact the tracking of outcomes over a period of time.
• Current treatment cost offset. The cost of a current treatment regimen may depend on the disease state or severity and may not be the same across all members receiving costly gene therapy. For some target conditions, there may be greater healthcare expenses for “untreated” conditions than compared to other target conditions.
• Long-term benefits. The gene therapies, for example, are expected to be a one-time dosage, but these products are all new to the market and there are no long-term studies to determine the actual, real-world effects.

Year-End Package Could Increase Access to Addiction Treatment

Buprenorphine is a medication used to treat opioid dependence, designed to reduce the risk of future overdoses. It is available in buccal, intradermal, subcutaneous and transdermal dosage forms. Previously, a prescriber had to obtain a special waiver from the Drug Enforcement Agency before prescribing buprenorphine. Sponsors of the bill, Mainstreaming Addiction Treatment Act of 2021, advocated for removing the special waiver to promote access to this potentially lifesaving medication. There was a bipartisan effort to remove the special waiver requirements, thus making it easier for healthcare professionals to prescribe and provide patients access to buprenorphine. As of now, the bipartisan bill has passed.

Biden Signs Defense Bill with Vaccine Mandate Repeal

President Biden signed the National Defense Authorization Act (NDAA) for the fiscal year 2023, which includes a repeal of the vaccine mandate for military service members and a pay raise for military personnel. The NDAA includes a provision that repeals the previous mandate requiring service members to receive certain vaccinations, such as the COVID-19 shot. Instead, it will now give service members the option to opt out of certain vaccinations if they provide a statement acknowledging the risks associated with not being vaccinated. The NDAA also includes a 4.6% pay raise for military personnel — the largest increase in a decade. The bill also includes several other provisions, such as boosting the number of active-duty troops and increasing funding for various military programs.

Some States Move to Ban Copay Accumulator Programs

Avalaere’s study predicts the potential impact of state bans on copay accumulator programs on the commercial insurance market in the United States. Some insurers and pharmacy benefit managers use copay accumulator programs to manage the use of certain types of drug coupons and other financial assistance programs provided by pharmaceutical manufacturers. Accumulator programs ensure that only money paid out of pocket by an individual counts towards insurance accumulators. The analysis estimates that 13% of commercially-insured lives in the US would be affected by such bans, which have been proposed or enacted in several states. The study further suggests that these bans may significantly impact patient access to certain medications and could lead to higher costs for both patients and payers.