Take a look at MHE's September issue where we feature, "Medicare Advantage Plans, on a Roll, Could See Some Cuts," as our cover story this month!

Managed Healthcare Executive September Issue

An FDA advisory voted unanimously in favor of a narrower endorsement of booster shots of the Pfizer COVID-19 vaccine after voting 16-2 against a broader recommendation that would have included everyone 16 years and older.

The second vote on the narrower question endorsed a third shot of the Pfizer vaccine for those 65 and older and at higher risk of suffering a serious case of COVID-19. 

The committee was also unanimously in favor a booster short for healthcare workers and others at high risk of occupational exposure to COVID-19, although that result was in a poll of the committee and not a formal part of the questions they voted onl

The committee's vote was closely watched for many reasons, chief among them because it figured into the high-stakes question of whether the FDA (and CDC) would go along with the Biden administration's push for a booster shots to start next week. 

The vote of the FDA committee of outside experts — known as the Vaccines and Related Biological Products Advisory Committee — is not binding but the agency is expected to follow its recommendations. CDC has a separate committee, called the Advisory Committee on Immunization Practices, that sets the federal government's official vaccine recommendations.

Reaction to the committee votes among the experts who tweet about COVID vaccination was, by and large, favorable. 

“The vote question was set up to fail, calling for a blanket approval for all age 16+ (related to aggressiveness Pfizer EUA request)," tweeted Topol. "How could that possibly be voted for in favor when such broad data do not exist anywhere? Of course the vote was 16 to 3 against." (Topol got the tally of the first vote slightly wrong). 

Later, he said the votes were a "very good outcome for this FDA Advisory Committee following what data are available.

Ashish Jha, dean of the Brown University’s School of Public Health who has emerged as an influential voice on COVID-19, tweeted that data for higher risk people (those older 60 and those with multiple chronic diseases) is compelling but "data for 16 to 59-year olds getting booster is meh.” Jha called the unanimous vote for those 65 and older and at high risk a “good result, clearly consistent with the evidence and this outcome should never have been in doubt.”

Leana Wen, a former Baltimore health commissioner and a CNN medical analyst, tweeted that the committee came to "reasonable middle-ground decision." 

Pfizer has argued that data show that protection from its two-shot vaccine wanes. The meaning of evidence from Israel, where a booster shot has been used, was debated by FDA advisory committee.  

Two top FDA vaccine officials, Marion Gruber and Philip Krause, were among the authors of a

 published on Monday that said current evidence didn't support booster shots while acknowledging that may eventually be necessary. Part of their argument is that even if antibody levels fall off, there are other parts of the immune response that will protect people, especially against a serious case of COVID-19.

Articles

Committee's two votes are only recommendations but a narrower booster emergency use authorization now seems likely.

FDA Advisory Panel Votes Against Blanket Booster but for Third Shot for Elderly, Those at High Risk of Severe COVID-19

The three-day 2021 Annual National Conference of the Pharmacy Benefit Management Institute® this week featured more than dozen speakers discussing everything from interoperability to digital therapeutics to preparations for switching PBMs to the COVID-19 pandemic.

 Speaker after speaker mentioned that specialty drugs — often, but not always, biologics for rare diseases — now account for half, or nearly half, of drug costs even though they amount to 2% to 3% of all prescriptions. So how to tame the specialty drug trend? There were lots of suggestions. 



Paula Bickley and Ashleigh Burdette of Biologics by McKesson

, a specialty pharmacy that focuses on cancer patients, discussed how their company’s care plans for patients reduce hospitalizations and avoid wasteful prescribing. Joshua Fredell, Pharm.D., and Tierra Ford, Pharm.D., of CVS Health discussed the three principles that the company uses to guided specialty drug management: start therapy with certainty (i.e., use quality evidence), aim to eliminate waste throughout treatment, and intervene when needed. Ford discussed the example of program to reduce the number of high-dose Stelara (ustekinumab) prescriptions.


There may be better ways to crunch the numbers.

 Managing drug costs means dealing with the numbers that reflect those drug costs. 

 made a case for his company’s net economic value assessment that factors in formulary and utilization management effectiveness, not just costs after rebates. Matthew Gilbert, Pharm.D., of president of 

, gave a spirited argument against the industry’s reliance on the average wholesale price and lack of specific drug prices and for the National Average Drug Acquisition Cost (NADAC), a data set of prices reported by retail pharmacies.


Data is king in managing drug costs and healthcare overall. But it tends to be walled off into small, tightly controlled fiefs, so getting a full picture, going by the numbers, is nigh impossible. 

On the first day of the conference, 

 vice president of industry relations and government affairs at CoverMyMeds, thumbnailed federal rules that are supposed to promote interoperability and “data fluidity” and efforts by various groups to create standards that are supposed to enable that to happen. Fredell, at CVS, spoke about the importance of “connectivity” and the information coming from the electronic health records and from patients.


The keynote speaker, former FDA commissioner Scott Gottlieb, M.D.,

 had an upbeat appraisal for the next few months of the COVID-19. While not explicitly backing a booster shot — Gottlieb is on the Pfizer’s board of directors — the country’s former top drug regulator said a booster would bring up antibody levels seen after the second shot of the two-shot RNA vaccines (Pfizer’s and Moderna’s) and make vaccination live up to the promise of protecting people against infection, not just serious illness from COVID-19. 

But Gottlieb also predicted a future of endemic COVID-19 and said the country will need to adjust to infectious respiratory illnesses as health threats. In his rapid-fire, chart-filled presentation, 

, vice president of industry relations at IQVIA, noted how the near-absence of flu cases last year was one of the factors that drove down medical utilization. Long showed data from Australia that suggested that the number of flu cases during the 2021-22 season may again be much lower than normal.


 Size matters apparently matters a lot in pharmacy benefit as the industry has become increasingly consolidated. Kerri Tanner, RPh, Pharm.D., senior vice president, specialty product, at Optum, made a case for a centralized, coordinated approach to drug benefit management as she described a program called Optum Specialty Fusion that has been shown to save Optum clients $15 per member, per month in specialty drug spend. 

Tanner compared specializing in an aspect of pharmacy benefit to removing a piece in game of Jenga. But Javier Gonzalez, Pharm.D., chief growth officer at Abarca, kicked off the second day of the conference taking a different tack as he discussed the advantages of bringing some aspects drug management in house, unbundled and perhaps in an à la carte fashion.


Happy to be unZoomed and resume being back in person. 

The meeting was conducted in hybrid fashion with some attendees in person and others online. Almost every in-person speaker said this was one of the first, if not 

 first, meeting they had traveled to in person since the beginning of the pandemic. Some joked about being rusty and awkward in social situations, but virtually every speaker began their presentation by saying how happy they were to be addressing people in person again.

The specialty drug spend and data flow and connectivity were among the themes of the presentations given at the hybrid conference this week in Orlando, Florida. 

6 Takeaways From 2021 PBMI Annual National Conference

The health benefit of AstraZeneca’s tezepelumab when added to standard of care therapy for severe asthma is comparable or better than standard care alone, but estimated costs could exceed standard cost-effectiveness measures, according to a 

 from the Institute for Clinical and Economic Review (ICER), the independent cost effectiveness and drug pricing group in Boston.,

 about 25 million people in the United States, according to the CDC, and about 10% of patients have severe asthma. The condition leads to about 1.6 million emergency room visits, 180,000 hospitalizations, and 3,500 deaths each year in the United States. The societal costs are estimated to be $81.9 billion, including missed days from work and school, medical costs, and mortality.

Tezepelumab is a potential first-in-class therapy for severe asthma. It is a monoclonal antibody that inhibits the action of TSLP, an epithelial cytokine that plays a critical part in the inflammation associated with severe asthma. TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles, and it has been correlated with disease severity.

 a biologics license application (BLA) for tezepelumab to the FDA in July 2021 and the regulatory agency granted the therapy priority review. The Prescription Drug User Fee Act (PDUFA) date — the date by which the FDA is supposed to make a decision on the application — is in the early part of 2022. 

The filing was based on results from the PATHFINDER clinical trials, including results from the pivotal NAVIGATOR phase III trial. In that trial, tezepelumab demonstrated superiority across the primary and key secondary end point in a broad population of patients with uncontrolled asthma while receiving treatment with medium- or high-dose inhaled corticosteroids.

ICER compared tezepelumab with Genentech’s Xolair (omalizumab) for patients with allergic asthma and Sanofi’s Dupixent (dupilumab) for patients with eosinophilic asthma. Reviewers also compared the efficacy of tezepelumab and Dupixent in patients dependent on chronic oral corticosteroids.

ICER reviewers found that for patients with eosinophilic asthma, improvements in symptom scores and reductions in annualized asthma exacerbation rate (AAER) were similar to the results seen with Dupixent. For patients with allergic asthma, improvements in symptoms were similar to those seen in older trials of Xolair while reductions in AAER were somewhat greater than with Xolair.

In a separate randomized trial of tezepelumab in patients with steroid-dependent asthma, patients treated with tezepelumab were not more likely to reduce their oral corticosteroid dose than placebo.

According to ICER findings, treatment with tezepelumab results in gains of 1.09 quality-adjusted life years (QALY) and 1.12 equal value life years (evLYs). From a health system perspective and using a placeholder price of about $27,860 per year, reviewers estimated a cost of $430,000 per QALY gained and $422,000 per evLY gained, which would exceed usual cost-effectiveness thresholds.

ICER reviewers also pointed out that trials for tezepelumab didn’t enroll enough Black patients to adequately assess how well the medication works in the  Black Americans, which suffers disproportionately fromsevere asthma is more prevalent in this population.

ICER will be taking public comment on the draft analysis through Oct. 14, 2021, and a virtual meeting on the report is scheduled for Nov. 19, 2021.

Tezepelumab, which is being currently reviewed by the FDA, provides small improvements in daily symptoms and quality of life but is only modestly cost-effectiveness at the anticipated price, according to the cost-effectiveness group's calculations.

ICER Foresees AstraZeneca’s Tezepelumab for Severe Asthma As Being Only Modestly Cost Effective

A patient rests comfortably in a hospital bed. Everything seems fine. Neither the patient nor the doctor or nurses realize he is about to take a life-threatening turn for the worse. Within hours, he will be septic, and his care team will race to begin aggressive fluid resuscitation and antibiotics

Yet, although the patient’s doctor and nurses do not see sepsis coming, someone else does — or, more accurately, some

 else does. The patient’s electronic health record (EHR) includes an artificial intelligence (AI) tool that detects patterns imperceptible to the patient’s human caretakers. It duly sends an alert to his doctor and nurses. What could have been a shocking deterioration is instead averted.

It sounds futuristic, this kind of thing that AI could do. But algorithms are already detecting hard-to-anticipate conditions such as sepsis in hospitals, and lives are already being saved. In fact, the underlying idea — that a set of data, put together in context, can help predict outcomes — is already very much a part of medical thinking.

“A lot of these concepts, they’re not new to medicine,” says Yasir Tarabichi, M.D., MSCR, director of clinical informatics for research support at MetroHealth, a safety net healthcare system in Cleveland.

AI and machine learning based on huge medical data sets are just the latest iteration of risk stratification, Tarabichi says, which is something as old as medicine itself. Before AI, patients could be given risk scores based on simple scoring tools and scales. AI has created the opportunity to score patients using thousands of measurements not previously available, much less analyzable. “It was simpler before, because it was more of a point-based system,” Tarabichi says. “Now it (has become) a lot more complicated.”

With opportunity comes challenges. One of the main challenges with AI is dealing with the onslaught of new products. Prem Thomas, M.D., medical director of data analytics and medical information officer at Yale New Haven Health in Connecticut, said he and colleagues get visits from software representatives the way doctors have historically received visits from drug company sales reps. “It’s interesting,” he says. “We have our weekly medical information officers’ meeting, and typically there’s somebody (from a technology vendor who) wants to present to us during that time.”

The companies hawking their AI wares range from entrenched players such as Epic Systems, the largest EHR company in the United States, which markets a sepsis prediction model, to tiny startups that have little, if any, experience in healthcare. Increasingly, tech giants such as Apple and Google have tried to gain a foothold in the healthcare technology sector, often with an
AI focus.

The utility of AI in healthcare settings extends beyond clinical decision support tools such as the sepsis model. One area Thomas has been examining uses AI to make operating room scheduling more efficient. Currently, the time slots that surgeons request for routine procedures such as appendectomies are often imprecise.

“The surgeon asked for two hours,” Thomas says, “but based on the data for that surgeon and the location where they are going to be (performing the operation), can we be more accurate in how long it’s going to take and, hopefully, minimize things like delays for other patients and other surgeons?”

Houston Methodist Hospital turned to AI when it was preparing to receive COVID-19 vaccines, according to LeTesha Montgomery, M.H.A., RN, the hospital’s vice president for operations and patient access. The hospital knew they would be facing a “tsunami of phone calls” from patients and members of the public asking questions or wanting to sign up for the vaccines, Montgomery says. “With predictions of increased volume reaching 300% to 400%, hospital leaders knew we needed a solution that would manage the flood of vaccine-related phone calls without impacting usual operations,” she says.

The hospital used Syllable, a conversation AI voice assistant, to automate work flow and conserve resources by making it easier for patients to find a wide array of answers without needing to speak to a human being. It also used AI to handle in-person traffic. Visitors to the facilities were screened by the temperature-monitoring platform Care.ai by standing in front of a tablet equipped to scan for fevers. “This contactless technology not only helped with conserving staff resources, but it also speeds up screening measures at point of entry,” Montgomery says.

One reason Houston Methodist was able to implement its COVID-19 strategies fast is because it has set up an infrastructure to quickly review and vet new technologies. The Center for Innovation, launched in 2018, has a group called DIOP, which stands for Digital Innovation Obsessed People, made up of roughly half operational staff and half information technology staff. The group is charged with developing strategies for broad-scale implementation or “failing fast” — quickly identifying technology that is not a good fit. “The results of focusing on innovation before it was essential to a pandemic such as COVID-19 enabled our hospital system to embrace new technology, including AI, more seamlessly,” Montgomery says.

Still, the stakes for AI implementation vary depending on its proposed use. A temperature-screening device that stops working might mean a staff member gets temporarily reassigned to thermometer duty. An errant AI system designed to help clinicians make treatment decisions could harm patients, even kill them.

Tarabichi said it is important that the public understands that hospitals do not take AI lightly.

“We don’t just blindly adopt new technology,” he says. “We make sure it’s going to work for us.”

For instance, before implementing the Epic sepsis model, MetroHealth ran the program in the background for an entire year, disabling the alerts but collecting data. Before they toggled it live, the health system wanted to make sure it worked and had a meaningful benefit. At the end of the year, they adopted the technology but limited its use to the emergency department.

Thomas says that kind of slow, evaluative approach is key to AI integration. It means taking the time to understand how an AI system works, getting an idea of the data sets used by the vendor and tailoring the program’s settings to the health system’s needs.

In other words, it takes time and money — and more time. But Thomas says the expense is worth it.

“I would recommend that community hospitals or academic hospitals invest the resources in having a redesign committee review what this model is purported to do for you and then think through how to operationalize it,” he says. Yale New Haven’s redesign committee, for instance, is an interdisciplinary team whose members include intensive-care unit nurses, emergency department doctors, inpatient nurses and other professionals, as well as analytics staff.

But a health system’s ability to carefully evaluate an AI system isn’t just a matter of staff expertise and representation. It also requires having access to enough data and software to fully understand a product. Because AI products are proprietary software marketed by for-profit companies, there can be tension between the company’s desire to keep proprietary information private and a healthcare system’s need to fully understand the tools they are using to take care of patients. 

An example of that kind of conflict had a public airing this summer when investigators from the University of Michigan reported findings of their independent evaluation of Epic’s sepsis prediction tool in 

. Their research suggested that the product is less accurate at predicting sepsis than what the company claims in its marketing materials. The findings were controversial, in part because the sensitivity of the AI tool depends on the settings put in place. Epic disputed the findings, saying that it works closely with users to ensure the product meets their needs and to provide access to the data necessary to evaluate the model.

Tarabichi has submitted his own paper, soon to be published, which contradicts some of what the Michigan investigators found. Yet, even as experts disagree about the particular product, this raises important questions about the limits of using proprietary models.

“The increase and growth in deployment of proprietary models has led to an underbelly of confidential, non-peer-reviewed model performance documents that may not accurately reflect real-world model performance,” wrote the corresponding author of University of Michigan study, Karandeep Singh, M.D., M.M.Sc., and his colleagues.

In the case of Epic’s sepsis model, both Thomas and Tarabichi said they were satisfied that they had access to the information they needed to evaluate the product, though they both said information from the company was just one component of their implementation process.

Tarabichi cautions against hospitals “jumping on the bandwagon,” of using popular AI without first validating it and testing it in their own system. In a smaller community hospital setting, validation may not need to be as complicated as it might at a top academic medical center with a diverse patient population.

“Randomized controlled trials are the highest level of evidence, but lower down that hierarchy is pre- and post- assessment,” he says. “Run it for a couple of months and then evaluate. What changed? Can you do better?”

For Thomas, it is not just about choosing the right AI system but also about being thoughtful about when and where AI is actually needed. He and his colleagues reference a “Mad Lib” created by Michael Draugelis, the chief data scientist at Penn Medicine in Philadelphia. It goes like this, Thomas says: “If I were [a physician, a physician’s assistant, a nurse, an operating room scheduler] in the health system and I knew ____, I would do ___ to change ____. “Before we start on any project now, we say, ‘fill in the blanks,’ ” Thomas says. “Because if we don’t have a good answer for those, then we shouldn’t be investing the time and effort to go through with the project.”

Montgomery agrees, saying technology cannot displace patients’ status “at the center of everything we do.”

“AI isn’t meant to solve all the challenges in the healthcare setting,” she says, “but where these applications make sense, where they provide real benefits to our patients, that means it’s reaching its full potential.”

Artificial intelligence is improving healthcare methods and insights. But when used incorrectly, AI is rife with pitfalls.

AI: Beyond the Buzz 

A drug used to treat advanced breast cancer may offer a new treatment option for 

, a rare blood cancer, according to a new study. The research was done in a mouse model, so the finding is preliminary and useful for guiding research, not treatment decisions.

The medication, Ibrance (palbociclib) may be able to prevent the scarring of bone marrow that existing treatments for myelofibrosis cannot, according to the study published in 

. The scarring disrupts the marrow’s production of blood cells and causes severe anemia that leaves patients weak and fatigued, and often makes blood clotting difficult, leading to an enlarged spleen, University of Virginia Health said in a 

Myelofibrosis occurs in approximately 1 to 1.5 of every 100,000 people, primarily those who are middle-aged or older. Patients with intermediate or high-risk cases typically survive only 16 to 35 months.

While Jakafi (ruxolitinib) is used to relieve patients’ symptoms, it does not offer significant reduction in bone marrow fibrosis and often loses its effectiveness with prolonged use, the researchers wrote. The new research suggests that pairing the drug with Ibrance may make for a superior treatment, UVA said.

“Current therapies only provide symptomatic relief without offering significant improvement of bone marrow fibrosis. So, there is a critical need to develop more effective therapy for myelofibrosis,” said Golam Mohi, Ph.D., the senior author of the study in the 

 and a researcher in the Department of Biochemistry and Molecular Genetics in UVA’s School of Medicine.

To that end, Mohi and other researchers identified CDK6, a regulator of cell cycle, as a new therapeutic target in myelofibrosis. “We demonstrate that CDK4/6 inhibitor palbociclib (Ibrance) in combination with ruxolitinib (Jakafi) markedly inhibits myelofibrosis, suggesting this drug combination could be an effective therapeutic strategy against this devastating blood disorder,” he said in the press release.

Ibrance, dampens the activity of bone marrow in patients with metastatic breast cancer, reduced bone marrow scarring in two different mouse models of myelofibrosis. It also decreased the abnormally high levels of white blood cells seen in myelofibrosis and shrank the mice’s enlarged spleens.

Combining the drug with Jakafi produced a number of positive outcomes, the researchers said. The combination restored the bone marrow and white blood cell counts to normal and dramatically reducing the size of the mice’s enlarged spleens.

The study results suggest support the clinical investigation of the palbociclib and ruxolitinib combination in patients with myelofibrosis, Mohi told 

®. “We are working with hematologists and oncologists at UVA Cancer Center to submit a proposal for clinical trial of this drug combination in myelofibrosis patients,” he said.

An Ibrance-Jakafi combination shows promise in a mouse model of myelofibrosis.

Ibrance Shows Promise in Treatment of Myelofibrosis  

Keith Loria is a contributing writer to Medical Economics.

More than 30 million Americans have diabetes, according to the American Diabetes Association, and many rely on insulin.

But insulin prices have been rising in recent years, and that has put many people with diabetes at risk because the price leads to people skipping doses or not taking insulin altogether.

The latest figures from the American Action Forum show that the price of insulin rose 14% a year, on average, between 2012 and 2018, and the past few years have followed this growth trajectory.

Many patients, policy makers and experts blame companies that manufacture insulin for dialing up the price of an established therapy. Sally Pipes, president and CEO of the Pacific Research Institute, a California-based think tank that favors free markets and limited government, says it’s easy to point the finger at pharmaceutical companies, but she finds fault elsewhere: in a dysfunctional market for insulin and many other prescription drugs and in pharmacy benefit managers.

“Pharmacy benefit managers — middlemen hired by insurance companies to manage their prescription drug plans — are driving those list prices up,” she asserts. The Pharmaceutical Care Management Association, the trade group for PBMs, says its member have done quite the opposite with programs that cap out-of-pocket costs or eliminate them. A spokesperson for the group says insulin makers have used patent extensions to avoid competiton.

In the summer of 2020, then-President Donald Trump signed an executive order aimed at reining in prescription drug costs, requiring federally qualified health centers and hospitals, which purchase insulin through the 340B Drug Pricing Program, to pass along any savings they receive from discounted drug prices to medically underserved patients. The Biden administration halted its implementation. The National Association of Community Health Centers, among others, expressed support for the new administration’s move, saying the Trump rule would not have lowered the cost of insulin (and EpiPens) for most Americans.

Some states are moving to control insulin prices. This summer, Colorado joined Illinois in passing legislation that caps out-of-pocket costs of insulin. Maine, New Mexico, New York, Utah, Washington and West Virginia are considering
similar legislation.

Prices may also come down if interchangeable biosimilars start coming on the market. In July 2021, the FDA designated Semglee (insulin glargine-yfgn) as an interchangeable biosimilar to Lantus (insulin glargine), a long-acting insulin analog. The designation means a pharmacist can switch the brand-name product for the presumably less expensive biosimilar, although state pharmacy laws can put some limits on interchangeability. Even so, the FDA approval should result in some competition between Semglee and Lantus and price decreases for patients and payers 

Keith Loria is a freelance writer in the Washington, D.C., area.

States are putting caps on prices, and Semglee, the first interchangeable biosimilar in the United States, may exert some downward pressure. 

Stemming the Rising Tide of Insulin Prices 

HER2-Positive mBC Standard of Care: Chemotherapy Plus HER2-targeted Therapy

For patients with newly diagnosed HER2-positive mBC, Krop and Patt explained that the current standard-of-care regimen includes both chemotherapy and HER2-targeted therapy, as the combination has been demonstrated to be more efficacious than using either alone. They added that treatment typically involves a taxane, such as Taxol (paclitaxel) or Taxotere (docetaxel), combined with the monoclonal antibody Herceptin (trastuzumab), but recently, chemotherapy combined with dual HER2-directed therapies, Herceptin and Perjeta (pertuzumab) has demonstrated increased survival benefit.

There have been several advancements in the therapeutic landscape of HER2-positive mBC, many of which have created additional treatment options in later lines of therapy. Nerlynx (neratinib) in combination with Xeloda (capecitabine) was approved by the FDA in February 2020 for adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

 Soon after, in April 2020, the FDA approved Tukysa (tucatinib) in combination with Herceptin and Xeloda for the treatment of adults with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

 Later that same year in December, the FDA approved Margenza (margetuximab-cmkb) in combination with chemotherapy for adults with HER2-positive mBC who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.

Additional combinations are being explored in ongoing clinical trials in patients with HER2-positive mBC. The phase 3 DESTINY-Breast09 trial aims to evaluate Enhertu (trastuzumab deruxtecan) with or without Perjeta versus the standard-of-care regimen (taxane, Herceptin and Perjeta) in the first-line metastatic setting. The primary end point of the study is progression-free survival (PFS; assessed by blinded independent central review); some of the secondary end points include investigator-assessed PFS, overall survival, objective response rate, duration of response, time to second progression or death and health-related quality of life.

 Previously, Enhertu was granted accelerated approval by the FDA in December 2019 for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

Although the therapeutic landscape for HER2-positive mBC has experienced recent innovations, numerous challenges have the potential to affect the overall delivery of care.

Challenges With Current Treatment Approaches

Most patients with HER2-positive mBC will be treated with chemotherapy in combination with HER2-directed therapy, but clinicians must still make treatment decisions that consider patient-specific factors, as well as systemic obstacles that may affect the delivery of appropriate care.

Krop and Patt agreed that therapeutic approaches in HER2-positive mBC can be associated with treatment toxicity, which can have lasting effects on the patient’s quality of life. Numerous patient-driven factors can influence how therapy is tolerated, including patient age, performance status, comorbidities and location of metastases, according to Patt. She added that when patients are overburdened with toxicity from treatment, they may be less able to maintain productivity in the workforce, compounding the financial burden of treatment.

The financial burden of treatment can be an obstacle to care. "These drugs are all incredibly expensive, and it’s a big challenge for the healthcare industry and for our society," Krop noted. "It’s a societal problem that we’re going to have to deal with.” Patients with HER2-positive mBC are typically treated using combination regimens, which can compound the overall cost of therapy. Many of the available HER2-targeting agents are costly, with those entering the treatment landscape more recently being particularly expensive. However, treatment may still be cost prohibitive even when biosimilars enter the market, Patt added. Additionally, she indicated that the overall cost of treatment is also likely to increase as HER2-directed agents have the potential to receive FDA approval for use in earlier lines of treatment.

Both Krop and Patt emphasized that it is critical for clinicians to recognize that there may be challenges associated with insurance coverage when it comes to treating HER2-positive mBC. Among patients with commercially available insurance, prior authorization can pose a significant challenge, delaying appropriate therapy and imaging. Patients with Medicare may encounter unique obstacles to care related to formulary choice, reimbursement and single-dose vials. Patt further explained that patients who are uninsured are likely to encounter significant barriers to appropriate treatment; there may be charitable care pathways available, but these are highly variable by region and other factors.

According to Krop and Patt, the use of chemotherapy in combination with HER2-directed agents can increase the overall treatment burden for patients with HER2-positive mBC. When on combination therapy, patients may have medications with multiple routes of administration and dosing cycles. This can be challenging for patients to keep track of, so they sometimes require additional coaching about when to take their medication at home and when to come into the clinic for infusion, Krop explained. To accommodate the difficulty of managing complex treatment regimens, Patt noted, “When you use those other agents at different cycles, sometimes people do consider alternative schedules of these therapeutic interventions to try to keep treatment more convenient for the patient.”

Patients with HER2-positive mBC may also encounter obstacles associated with their overall healthcare system utilization, particularly because disease management typically involves monitoring and treating potential side effects of therapy. Patt described how patients require follow-up echocardiograms to evaluate their cardiac function, for example. Managing this side effect of treatment involves numerous added touch points with the healthcare system. Even without side effects complicating treatment, additional steps such as surgical or radiological intervention may complicate already challenging cost and access issues, Patt added. She explained that the scope of healthcare utilization required by patients with HER2-positive mBC can exacerbate problems associated with overburdened and understaffed healthcare systems. This can result in critical delays to receiving lab results, scheduling imaging and performing biopsies, she noted.

Patt described how, in the era of COVID-19, there have been pervasive decreases in cancer screening, biopsies, diagnoses and subsequent therapeutic intervention. In addition to these reductions in cancer care diagnoses, she said, there have been challenges with managing patients with metastatic disease: “We have been burdened by a global pandemic, (so) all the work-up (that) patients need in the metastatic setting is a little delayed. It’s taking longer. There are capacity limitations in the ability to do biopsies or additional imaging.”

Physicians have needed to adjust their treatment strategy to accommodate existing patients. According to Krop, some healthcare providers have reconsidered the use of immunosuppressive regimens or started using longer-acting therapies to minimize the number of clinic visits necessary. Visiting nurse services and phone- or internet-based forms of communication have also been used, but Krop indicated that the degree to which these will remain cost-effective or feasible at scale post-pandemic is unclear.

National Comprehensive Cancer Network (NCCN) Guidelines

Krop commented on the value of current treatment guidelines for HER2-positive mBC by stating, “If you look at the NCCN Guidelines, they’re not very directive.” He explained that this can make it challenging to navigate patient-specific factors when deciding whether to use upfront chemotherapy versus an alternative therapy. Current guidelines do not specify which patients may derive benefit; they provide helpful guardrails, but there are many reasons why a patient’s treatment plan may deviate from the guideline-directed approach.

Taking a value-based approach to the care of HER2-positive mBC requires an analysis of the potential benefits and costs of treatment to provide appropriate care for patients. For the future management of patients with HER2-positive mBC, both Krop and Patt agreed that the healthcare system should provide patients with treatment that is both medically effective and cost effective to maximize disease control without causing undue burden on patients and the healthcare system.

Patt addressed value-based care in HER2-positive mBC: “The most important value-based initiative is that patients go on to live disease free. You can’t discount that because I think superior efforts and the best possible evidence for disease control [are] the most appropriate value-based choices," she said. “Patients with HER-2 positive metastatic breast cancer can benefit from these long disease-free intervals (for) more than a decade. And so I think a question remains: 'How can we give the most effective therapy upfront, and then keep them on some chronic therapy in perpetuity to keep their disease controlled, and (do this in) the most cost-efficient way?' And with so many innovator products in this space, I think we're going to have better answers there in the next years to come.”

1. Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study.

. 2020;21(4):519-530. doi:10.1016/S1470-2045(19)30863-0

2. FDA approves neratinib for metastatic HER2-positive breast cancer. FDA. February 26, 2020. Accessed August 5, 2021. https:// 

www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neratinib-metastatic-her2-positive-breast-cancer

3. Nerlynx. Prescribing information. Puma Biotechnology; 2021. Accessed August 5, 2021. 

https://nerlynxhcp.com/pdf/full-prescribing-information.pdf

4. Tukysa. Prescribing information. Seagen; 2020. Accessed August 5, 2021. 

https://seagendocs.com/TUKYSA_Full_Ltr_Master.pdf

5. FDA approves margetuximab for metastatic HER2-positive breast cancer. FDA. December 17, 2020. Accessed August 5, 2021. 

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-margetuximab-metastatic-her2-positive-breast-cancer

6. Margenza. Prescribing information. MacroGenics; 2020. Accessed August 5, 2021. 

https://www.margenza.com/pdf/prescribing-information.pdf

7. DESTINY-Breast09 head-to-head first-line phase 3 trial of Enhertu initiated in patients with HER2 positive metastatic breast cancer. News release. Daiichi Sankyo. June 14, 2021. Accessed August 5, 2021. 

https://www.daiichisankyo.com/files/news/pressrelease/pdf/202106/20210614_E_ver2.pdf

8. Trastuzumab deruxtecan (T-DXd) with or without pertuzumab versus taxane, trastuzumab and pertuzumab in HER2-positive metastatic breast cancer (DESTINY-Breast09). ClinicalTrials.gov. Updated August 2, 2021. Accessed August 3, 2021. 

https://clinicaltrials.gov/ct2/show/NCT04784715

9. FDA approves fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive breast cancer. FDA. December 20, 2019. Accessed August 5, 2021. 

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2-positive-breast-cancer

10. Enhertu. Prescribing information. Daiichi Sankyo; 2021. Accessed August 5, 2021. 

https://dsi.com/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true

In this Managed Healthcare Executive® KCast, Ian Krop, M.D., Ph.D., oncologist and associate professor of medicine at Dana-Farber Cancer Institute in Boston, and Debra Patt, M.D., Ph.D., MBA, executive vice president at Texas Oncology in Austin, provide key insights into the value-based care model for patients with HER2-positive metastatic breast cancer (mBC). This article summarizes the highlights of the discussion.

Value-Based Decision-Making in Metastatic Breast Cancer

Retailers such as CVS Health and Walgreens Boots Alliance may force traditional providers to rethink the way they deliver healthcare. The drugstores ramped up care during the heart of the COVID-19 pandemic, often providing more convenient and less costly alternatives.

“Traditional providers have to think like retail providers going forward: convenient, transparent and cost-effective,” says Arielle Trzcinski, a principal healthcare analyst at Forrester, a research and advisory company. The retail clinics tend to be less expensive for consumers than traditional providers and urgent care centers, Trzcinski notes, and the walk-in access is an advantage over having to schedule an appointment.

By offering COVID-19 testing and vaccinations and providing medical care at their in-store clinics, retailers built up “a lot of goodwill that they will carry forward beyond the pandemic,” Trzcinski adds. “It’s an opportunity for them to continue to build on the trust consumers have started to have in them.”

A survey of 2,200 adults conducted in the spring of 2021 by the Morning Consult, a survey company, found that 35% of the respondents had received healthcare in person at a retail clinic since the pandemic began in early 2020 and that 8% had received care at the clinics often.

A different survey of 500 consumers and 250 retail healthcare executives released by the technology company UPshow found consumers were inclined to go to retail health clinics during the pandemic because they wanted to avoid doctors’ offices that might be crowded. The clinics in the chain drugstores also allowed them to combine medical care and shopping so they could limit trips away from home. Not all of the findings from the UPshow survey are positive for retail health clinics. Almost half (47%) of those surveyed indicated that they were not “completely confident” in the quality of care provided at retail health clinics.

Although CVS and Walgreens have made sizable bets on retail healthcare being part of their futures, their approaches vary. CVS is focusing on developing in-store HealthHUBs where its customers can get a variety of healthcare services, including primary care for chronic conditions and behavioral healthcare. Rather than developing its own healthcare services, Walgreens has focused on relationships with other providers, including a partnership created last year with VillageMD to develop doctors’ offices in its stores. But Dan Clarin, managing director at Kaufman Hall, says neither Walgreens nor CVS “offers every service to every customer on their own — they’re a convener of services.” He compares the companies to Amazon as a platform to connect consumers with the products they want.

The drugstore chains don’t have the retail healthcare business entirely to themselves. Walmart has set up clinics in some of its stores, offering a variety of services, including dental, optometry, primary care and X-rays. Walmart has acquired MeMD, a telehealth provider. With that acquisition, Walmart has filed paperwork to do business in 37 states. according to the 

. The retailers are hopeful that their retail clinics will attract younger people, Clarin notes. The Morning Consult survey found that half of 18- to 34-year-olds had gone to a retail clinic during the pandemic, compared with just 1 in 5 of those aged 65 years and older. Younger consumers are less likely to have a primary care physician. They also have “less brand loyalty,” Clarin says, and focus on “experience and convenience.”

CVS has offered healthcare at its MinuteClinics for 25 years and has expanded to hundreds of locations inside its drugstores and in Target’s brick-and-mortar stores. But its more recent focus is on its HealthHUBs, which are billed as providing a wider array of services and services consumers will use over time. not just on an emergent basis. Part of the investment in HealthHUBs is a consequence of the company’s acquisition of Aetna in 2018 for
$69 billion. CVS calls itself “the leading health solutions company.”

“Over the last few years, we have pushed the boundaries to change people’s perception of their neighborhood drugstore, as well as to add value, offer more innovative services and provide convenient, affordable and accessible care,” Ryan Rumbarger, senior vice president of retail store operations for CVS Pharmacy, said in an email to 

.® At the end of the first quarter of 2021, the retailer had about 800 HealthHUBs, Karen Lynch, president and CEO of CVS Health, said in a call with investors. According to previously announced plans, the company’s goal was to have 1,500 of the hubs up and running by the end of 2021, but Lynch said the company would have about 1,000 in operation by that time.

CVS is offering COVID-19 vaccinations at 9,600 sites and providing testing for the virus at thousands of locations, many of which serve vulnerable communities, Rumbarger said.

CVS’ most recent move is adding licensed therapists at certain HealthHUB locations as demand for behavioral health services has soared in light of the pandemic.

Walgreens is focusing on partnering with providers In late 2020, it announced it was closing 150 clinics that it operated on its own. It still partners with local health systems to operate clinics. But the company’s major play in retail healthcare is its partnership with VillageMD, a primary care company headquartered in Chicago. The plan is to develop at least 600 VillageMD clinics, which operate under the name Village Medical, in more than 30 markets over the next four years, with hundreds more to follow, Rick Gates, Walgreens’ senior vice president of pharmacy, said in an email to 

. Currently there are more than 50 Village Medical clinics in Walgreens stores, most of them in the Sunbelt.

During the pandemic, the drugstore giant has conducted more than 8 million COVID-19 tests and provided more than 25 million vaccinations, Gates said. With millions losing their jobs, the company has lowered prices on hundreds of medications, he said,

Physicians and others have raised concerns about retail healthcare further fragmenting American healthcare. But Gates said data from the current Village Medical clinics indicate improvements in medication adherence and fewer emergency room visits, unnecessary hospitalizations and readmissions for patients with chronic conditions.

Walmart is calling its in-store clinics Walmart Health. The retail giant opened its first clinic in Dallas, Georgia, about 30 miles outside Atlanta, in 2019. Now it has clinics in stores elsewhere in Georgia, Texas and Arkansas. A price list on the company website for Dallas, Georgia, showed that a Walmart Health office visit costs $40; a dental exam with X-rays, $25; and a new patient therapy session, $60. The retailer’s wide range of services and low prices make it “convenient and cost-effective,” says Trzcinski, the Forrester analyst. Walmart has also priced many generic medicines at $4, which may help with getting people to take their medication as prescribed. “Cost is a huge barrier for folks being able to adhere to their medications,” Trzcinski says.

In late June 2021, Walmart acquired telehealth provider MeMD. “Today people expect omnichannel access to care, and adding telehealth to our Walmart Health care strategies allows us to provide in-person and digital care across our multiple assets and solutions,” says Cheryl Pegus, executive vice president of Walmart Health & Wellness, said in a news release announcing the planned acquisition.

Although Walmart doesn’t have as large a footprint as CVS and Walgreens do, it has a strong presence in rural areas, where access to healthcare may be hard to come by, notes Clarin.

is an independent journalist in Tampa, Florida, who writes about business and healthcare.

But CVS, Walgreens and Walmart differ in how they are setting up in-store health clinics.

Retailers Want to Provide You Healthcare, Not Just Sell you Stuff 

Jasper Health and its app for people who have survived cancer won the first Pharmacy Benefit Management Institute® Innovation Challenge.

The year-old company, based in New York City, has developed an app and platform that guides people through the experience of cancer survivorship. The app has biometric, medication monitoring and other features designed to help people who have received a cancer diagnosis to deal with the medical and mental health aspects of the disease.

Tim Patno, head of growth, said the Jasper has used social media to promote the app and benefited from digital equivalent of word of mouth. “The message has just been spreading because those who are using the product find significant value in it and are happy to share their stories,” he said.

The innovation was designed to foster a patient-centric innovation community. Projects and programs were judged by practicality, impact and forward-thinking focus. More than 20 companies competed in the challenge. Jasper Health was among the five finalists voted on yesterday by virtual and in-patient attendees of the 2021 Annual National Conference of the Pharmacy Benefit Management Institute.®

The prize for winning the challenge is a six-figure marketing and education campaign on the 

® and Formulary Watch multichannel media platforms. 

Jasper has just under 20 employees, according to Patno, but no revenues yet. Patno said the company is looking to enter into partnerships with payers, provider organizations and drugmakers. Yesterday, 

, a Dallas-based company that markets to elf-insured employers, announced that it had entered into a partnership with Jasper.

Patno said Jasper is aiming to become part of employers’ healthcare offerings by benefiting employees and reducing costs by, among other things, improving medical adherence. The current version of the platform allows patients to enter their medication schedule into the app. Patno said the goal is to eventually become integrated into electronic health record systems so medication schedules would be automatically entered.

The new company has developed an app and platform that guides cancer survivors through the experience of dealing with disease.










Jasper Health Wins 1st PBMI Innovation Challenge

Healthcare costs are increasing, but when it comes to drug expenditures, it’s only a small fraction of utilizers that account for more than half of their clients’ pharmacy spend, explained Joshua Fredell, Pharm.D., vice president of product development for CVS Health, in his presentation at the third and final day of the 2021 Pharmacy Benefit Management Institute® Annual National Conference.

New specialty treatments that can transform the lives of some patients are coming to market with increasingly higher price tags — some costing hundreds of thousands per year, Fredell noted.

“This means that cost management strategies must evolve to meet next-generation needs: a deliberate focus on curbing specialty spend without compromising plan member outcomes,” said his co-presenter, Tierra Ford, Pharm.D., senior clinical adviser, specialty client solutions, at CVS Health.

In their presentation, Fredell and Ford stressed how digital tools and platforms and connectivity are key to an effective utilization management strategy, so that the member gets the most clinically effective therapy while payers realize durable savings. 

Fredell emphasized the importance of connectivity  and that the CVS' specialty drug managers have connectivity, or access, to 70% of  electronic health record of providers and "digital connectivity" to 85% of members that can be used to go beyond routine messaging around issues like refill reminders.  

Fredell also listed three principles that CVS' management of specialty drugs follow: start with therapy with certainty,  eliminate waste throughout treatment (he mentioned earlier that 89% of the specialty drug spend is on existing treatment) and intervene when needed. Ford gave some examples of the principles in action. About 30% of Stelara (ustekinumab) may be on a higher dose than necessary. CVS member dosing limits to significant drop in high-dose prescriptions, resulting in $21.1 in gross savings.

Fredell also discussed several pilot projects, including one that provides support to rheumatoid arthritis on oral therapy with the goal of avoiding more expensive therapy if the oral therapy fails. Another pilot project is promoting phototherapy for psoriasis, which is a recognized, effective therapy that is under utilized, Fredell said. 

“Proactive monitoring and interventions, powered by advanced data analytics, can engage members with their treatment plans while preventing wasteful spend throughout the duration of therapy,” Fredell said. “(With) an integrated approach to specialty that goes beyond utilization, management can identify more opportunities to manage costs, improve member care and create a more seamless and connected experience for both members and providers.”

Fredell and Ford also discussed how clinically rigorous utilization management builds the foundation for a strong specialty cost-management program.

“Electronic health record connectivity enables greater visibility to accurate clinical data, including the exact diagnosis and most appropriate therapy for each member,” Ford said. “This makes the prior authorization approval more efficient and minimizes the need for additional provider outreach, supporting a more timely start to the most clinically appropriate therapy while eliminating waste and helping lower payer cost.”

“With specialty drugs accounting for a disproportionate share of the drug development pipeline, formulary and utilization management enhancements ensure that we drive to lowest net cost and get plan members started on a treatment plan based on clinical evidence,” Ford said. “Targeted interventions enabled by proactive monitoring and advanced analytics can help support better health outcomes by identifying members who may not be benefitting from their therapy, (maybe experiencing side effects or a worsening of their symptoms or are at risk for an adverse event.”

The pharmaceutical marketplace is dynamic, and specialty cost-management tactics must evolve to help payer stay ahead of trends and manage rapidly rising costs, Fredell said.

“Doing so effectively demands new approaches that go beyond traditional strategies and aggressive therapy denials, which may not deliver lasting savings,” Fredell continued. “Starting on the most appropriate therapy, ongoing monitoring, and intervening when needed to prevent and eliminate wasteful spend throughout the duration of therapy can help lower payer costs and support plan member health.”