Conference Insider: 2024 AMCP Nexus

With new drugs in the offing, treatment cost of ATTR-CM is projected to climb

By some accounts, spending worldwide on treatment of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) is projected to increase by more than 30% over the next several years, including in the United States. The cost on a per member, per month basis for U.S. healthcare plans is expected to remain relatively low, although it will increase as a share of the spending on the rare diseases categories, Timothy O’Shea, Pharm.D., M.S., director of specialty pharmacy at Horizon Blue Cross Blue Shield of New Jersey, said in a session devoted to ATTR-CM at the AMCP Nexus meeting.

ATTR-CM has caught the eye of drug developers, and several new drugs are in phase 3 trials.

Systemic amyloidosis is characterized by the buildup of amyloid deposits in the heart, kidneys and other organs. It can lead to organ dysfunction and death. The condition can be inherited or acquired. ATTR-CM is one type of systemic amyloidosis in which misshapen transthyretin (TTR) protein accumulates in the myocardium of the heart. ATTR-CM can cause a variety of heart problems, including heart failure and arrhythmias. Black individuals and men are disproportionately affected. The risk also increases with age and among those with a family history. There is a great deal of uncertainty about the prevalence of ATTR-CM in the U.S. because the condition may often go undiagnosed, but by some accounts at least 50,000 people are affected.

O’Shea said that the drug spend for ATTR-CM is low at this time because of the disease’s rarity. “But given that, even though utilization is going to be low [and] spend is going to be low, when we look at it in the aggregate of the rare disease category, we’re seeing big increases,” O’Shea said.

O’Shea said payers are grappling with overall rare disease spending by optimizing effective drug management and understanding the cost-effectiveness of therapies. For optimizing effective drug management, O’Shea mentioned a checklist for pharmacy benefits and medical benefits, which included utilization projection, formulary coverage, utilization management, pharmacy case management and assessment of real-world data.

In September 2024, the Institute for Clinical and Economic Review (ICER), a cost-effectiveness research organization, published a report on three drugs used to treat ATTR-CM: tafamidis, an oral drug; acoramidis, an oral drug; and Amvuttra (vutrisiran), delivered by subcutaneous injection. The ICER experts said there was a high degree of certainty of substantial health benefits from tafamidis and Amvuttra, and a high degree of certainty of at least a small health benefits from acoramidis.

Drug developers are interested in finding new treatments for ATTR-CM for a number of reasons, including the overall demographic trend toward an older population and an increasing number of diagnoses. Currently, there are five commercially available therapies. They cost from approximately $22,332 per month to $41,583 per month, so the cost for payers and patients is looming as an issue and could be an obstacle to care and coverage.

Tafamidis is the only currently FDA-approved therapy. Amvuttra, Onpattro (patisiran) and Wainua (eplontersen) are among the drugs used to treat other amyloidosis-related conditions that are used off-label to treat ATTR-CM, but a number of trials are underway with an eye toward getting FDA approval and having ATTR-CM as an indication.

“The drugs that we have available right now only work on stopping that production of the TTR protein to reduce further deposition in the tissue. We don’t currently have anything that can pull these fibril tissues, so recovery will be very slow for these patients because they have the wait for the body’s catabolic processes to break it down,” Tyler Sandahl, Pharm.D., a clinical pharmacy specialist at Mayo Clinic, said in the session.

Tyler Sandahl, Pharm.D.

Tafamidis, sold under the brand name Vyndamax, and tafamidis meglumine, sold under the brand name Vyndaqel, were approved by the FDA in 2019 for the treatment of ATTR-CM.

Diflunisal, a nonsteroidal anti-inflammatory sold under the brand name Dolobid, has been shown to be well tolerated in select patients who have adequate renal function in a single-center, retrospective study. The drug increased TTR concentrations and decreased left atrial volume index, according to Sandahl.

Patisiran has also been investigated as a treatment for ATTR-CM but was denied approval based on data from the phase 3 APOLLO-B study, which showed no statistically significant benefit in any of the secondary outcomes, including scores on a standardized survey designed to measure self-perception of health status, a composite of death from any cause, cardiovascular events and change in 6-minute walk test. Further, there were more infusion-related reactions, arthralgia and muscle spasms in the patisiran group compared with
the placebo.

Alnylam Pharmaceuticals Inc., the maker of Amvuttra, reported positive results from the HELIOS-B study of the drug as a treatment for ATTR-CM at the European Society of Cardiology Congress this summer. The results, published simultaneously in the New England Journal of Medicine, showed Amvuttra led to a 28% lower risk of death from any cause and recurrent cardiovascular events than placebo. Results on other end points tallied up in Amvuttra’s favor, and the number of adverse events was similar among those randomly assigned to be treated with Amvuttra and those randomly assigned to treatment with a placebo.

“[The company is] currently seeking expanded indication because right now vutrisiran is only approved [for hereditary transthyretin-mediated amyloidosis with polyneuropathy],” Sandahl said. “I don’t have information on when [an FDA approval] may be coming, but I would expect that in the coming months.”

The FDA is scheduled to announce whether it has approved acoramidis as a treatment for ATTR-CM in late November 2024. Although the development of the drug has had some setbacks, BridgeBio has reported positive results from the ATTRibute-CM trial recently, including a post hoc analysis at the Heart Failure Society of America’s annual meeting in September 2024.

Meanwhile, Ionis Pharmaceuticals is assessing eplontersen as an ATTR-CM treatment in the CARDIO-TTRansform trial, a multicenter, double-blind phase 3 study that is anticipated to enroll approximately 1,400 participants worldwide.

Use of copay offset programs expected to rise

Many employers are considering funding programs to offset healthcare costs, which can include copay accumulators, maximizers and other alternative funding programs. Even though a small percentage (5%) of employers are using alternative funding programs, approximately 60% said they are highly effective at managing healthcare costs, Laura Huff, vice president of Gallagher Research and Insights, said in a session at the AMCP Nexus meeting.

“More than half of all Americans receive insurance from their employers, so the decisions that employers are making about their benefit design have the potential to benefit millions of Americans,” said Kimberly Westrich, M.A., chief strategy officer of the National Pharmaceutical Council.

There are three main types of patient assistance programs: copay accumulators, maximizers and alternative funding programs. With a copay accumulator, amanufacturer’s copay assistance or coupon do not count toward the patient’s deductible and out-of-pocket maximum. Once the patient has used up the maximum amount available from the drugmaker, the patient pays out of pocket until the annual deductible and out-of-pocket maximum are met. Copay maximizers also involve manufacturer payments not counting toward deductibles and out-of-pocket maximums, but the maximum value of the manufacturer’s assistance programis applied evenly throughout the benefit year.

Kimberly Westrich, M.A.

With alternative funding programs, health plans exclude certain specialty drugs and steer plan members to separate alternative funding vendors for coverage. Some of those companies leverage drugmaker patient assistance programs.

“All of these programs have ethical trade-offs and considerations,” Westrich said. “They have been shown to lead to disruptions in access, exposing patients to unexpected [out-of-pocket] costs and reducing medication adherence.”

Employers know that pharmacy is very variable, so having these plans in place helps to plan cost management and predictability, said Cody Midlam, Pharm.D., director of WTW Health and Benefits. He added that maximizers are the most popular among employers, followed by accumulators and alternative funding.

Huff said a survey of 106 employers showed that they are most often concerned with the cost of pharmaceuticals for the employer (83%), cost of therapies that are new and have limited or no improvement of the outcomes (57%) and cost to the patient/employee (53%). As of 2024, approximately 42% of employers are using copay offset programs, with the number expected to increase to 50% by 2026. Of those employers, approximately 42% rated these programs to be highly effective for managing costs.

Approximately 36% mandate the use of specialty pharmacies for biologics, which is expected to rise to 55%; 30% use a biologic-preferred drug list, expected to rise to 53%; and 25% move all or some biologics coverage from medical to pharmacy benefit, expected to rise to 50%. Finally, though alternative funding is used by 5% of employers, 60% said that it is highly effective for managing costs. It is expected to rise to 12% by 2026.

Huff added that there is not much adoption of the alternative funding plans, but employers are looking into them. In 2023, 64% were not familiar with or had not looked into these programs, but in 2024, 30% looked into the programs but did not adopt them. In 2024, 5% are currently using them and 7% are planning to implement them in the next two years.

“It comes down to complexity. It’s going to create a lot of noise for members, who may receive it negatively,” Huff said.

The top three barriers to employers adopting alternative funding programs include the cost savings not worth exposing employees to additional administrative hassle (47%), not worth administrative complexities (41%) and contracting restrictions with existing vendors, such
as PBMs (31%).

Furthermore, patients are concerned with the delayed services of alternative funding programs, including an average of a two-month wait time. In the survey, 88% of patients are stressed when medication is denied by their plan, 71% are confused about why the medication was denied and 54% experience discomfort talking with their employer about medication needs or financial burdens to medication access. For specialty medication, 24% of patients reported that delays in receiving medication worsened their condition and 64% reported that waiting for medication led to stress and anxiety.

Alison Falb, J.D.

Another concern for employers is the legalities and ethics of the programs. In the presentation, Alison Falb, J.D., vice president of health policy at Applied Policy, said that copay accumulators have been the subject of rulemaking and lawsuits. For federal regulations, the Affordable Care Act, Notice of Benefit and Parameters (NBPP) and joint legislation from the Department of Labor, HHS and the Treasury all apply. “States can enact laws that are within their jurisdiction, but self-funded plans would not be subject to those laws, so federal legislation or regulation would be needed to affect those plans and standardize independent policy,” Falb said.

However, Falb added that many plans classify some drugs as non-
essential health benefits, which can exclude third-party copay assistance from the calculation of patient out-of-pocket costs. Currently, stakeholders are waiting for a ruling from CMS to address copay accumulator policies. In November 2024, NBPP is expected to propose a rule for 2026, with the final rule expected to be
released in April 2025.

More treatment options, more decisions to make, for schizophrenia

People with schizophrenia have a growing number of treatment options, including long-acting injectables (LAIs) and a newly approved anti-
psychotic that is the first one not to target dopamine receptors. The wide array of choices is seeding some uncertainty about which treatments to select and in what order.

“[The recommendations] offer a long list of ways to select an antipsychotic, but they aren’t going to tell you which one’s the best or which one to use first,” said Megan Ehret, Pharm.D., M.S., a professor in the Department of Practice, Sciences, and Health Outcomes Research at the University of Maryland School of Pharmacy and co-director of the Mental Health Program in the Department of Practice, Sciences and Health Outcomes Research there. “You don’t have the clinical research to look at head-to-head with all of… these various antipsychotics.” Ehret was a panelist at a session on schizophrenia at the AMCP Nexus meeting,

Ehret noted that the “positive” symptoms of schizophrenia, including delusions and hallucinations, are well known, but the full extent of the “negative” symptoms, such as lack of motivation, reduced speech output and flattened affect, are not as widely recognized. Schizophrenia also has cognitive symptoms, and the disease can have negative effects on physical health and social relationships as well as on a person’s mental health. People with schizophrenia also contend with social isolation and stigma. One overall health consequence is a reduced life expectancy of 13 to 15 years due to factors such as poor dietary habits, weight gain, smoking and comorbid substance use.

For payers, schizophrenia poses the challenges of managing the costs associated with a condition with higher-than-usual rates of emergency room visits and inpatient hospitalizations. Catherine Cooke, Pharm.D., M.S., a research associate professor and a colleague of Ehret’s at the University of Maryland School of Pharmacy and a panelist at the session, said the annual direct costs reach an estimated $24,913, of which $15,957 is related to healthcare and $8,956 to costs outside of healthcare. In addition, there are the indirect costs from caregiving and loss of employment. According to figures presented by Cooke, public payers bear most of the costs associated with schizophrenia. Of the patients with schizophrenia, approximately 19% are commercially insured, 43% are covered by Medicare, 35% by Medicaid, and 4% have no insurance, Cooke said.

Adherence is a long-standing problem among people with schizophrenia. Ehret told the audience at the AMCP Nexus session that meta- analyses and large trials have produced evidence about discontinuation rates, but the studies vary in design, so it is difficult to be certain about treatment algorithms.

Long-acting injectable (LAI) antipsychotics may help to reduce nonadherence. They are administered once every month, every six months or every year, depending on the drug. Examples of the LAI antipsychotics include paliperidone, sold under Invega Sustenna and other brand names, and risperidone, sold under Perseris, among otherbrand names

As for cost, LAIs are a trade-off, with pharmacy costs increasing because of their relatively high price while medical costs may decrease because of fewer emergency room visits and hospitalizations. The LAIs have many advantages, notably improved adherence, and real-world data that add to the evidence for their efficacy and safety. The challenges can include accessibility for patients.

Ehret discussed other drug classes, includingTAAR1 agonists, but noted that they did not have the desired effect. Nuplazid (pimavanserin), approved as a treatment for hallucinations and delusions associated with Parkinson’s disease psychosis, is being studied.

Researchers are also investigating glutamatergic modulators, including iclepertin and sodium benzoate, as possible schizophrenia treatments. Iclepertin has demonstrated improvements in cognition for patients, and sodium benzoate showed signs of improving cognitive symptoms but did not have an effect on negative symptoms.

The FDA approved Cobenfy (xanomeline and trospium chloride), previously known as KarXT, in September 2024. It is the first antipsychotic to target muscarinic receptors instead of dopamine receptors. Data from clinical trials suggests that Cobenfy does not have the side effects of drowsiness and weight gain that cause some people with schizophrenia to discontinue treatment with drugs that zero in on dopamine receptors. It has others, though, such as nausea, that could also lead to nonadherence.

Muscarinic agents that may follow in Cobenfy’s footsteps include emraclidine and NBI-1117568.

Humira biosimilars got off to a slow start. Has that changed?

Although there are now 10 biosimilars to Humira (adalimumab) on the market, they are struggling to compete against their brand-name reference product, the top-selling drug of all time, according to panelists at a session on the increasing adoption of Humira biosimilars at the AMCP Nexus meeting. “Penetration is very low compared to the number of products that we have on the market,” said Justin Bioc, Pharm.D., head of clinical pharmacy at Devoted Health, a health
insurance start-up.

Bioc said the contrastbetween biosimilars and the generics to small-molecule drugs is stark. “If you just think about generic drugs, once generics come out, and there are a few generics on the market, they generally take over in terms of utilization across your prescription volume, [but this] hasn’t been the case
with biosimilars.”

Amjevita (adalimumab-atto), launched in January 2023, was the first Humira biosimilar to come on the market in the U.S. Eight others followed in 2023. A tenth, Simlandi (adalimumab-ryvk), debuted in May 2024.

Another panelist, Sophia Humphreys, Pharm.D., M.H.A., director of system pharmacy formulary management and pharmacy clinical programs for Sutter Health, said some biosimilars were covered by payers in 2023 but not a high percentage. She noted that many Humira biosimilar manufacturers have used a dual pricing strategy, which meant the same biosimilar had two prices: a high wholesale acquisition cost (WAC) price to satisfy payers and maintain their rebates and a second WAC price that was, on average, 81% lower than Humira’s price. Even so, at the end of 2023, there was only a 3% adoption of biosimilars, she said.

In 2024, though, there have been different take about how to get biosimilars into the market, driven by pharmacy benefit manager (PBM) partnership strategies with the manufacturers, according to Bioc. Still, challenges to biosimilars remain, he said, including PBM rebates and preferred products, payer coverage, formulary tiers and the risk of shortages.

Large PBMs have started taking Humira off some of their formularies and replacing it with biosimilars, starting with CVS Caremark earlier this year. Optum Rx and Express Scripts followed suit. Prime Therapeutics announced in early October that it will begin offering its Blue Cross clients four Humira biosimilars as options. Humira biosimilar prescriptions have started to increase, and industry observers see the formulary changes as boosting them further, although there are still questions about who will reap the benefits because of the steps that some PBMs have taken to protect their business interests.

Humphreys said education, as well as cost, is important to the adoption of biosimilars. She also mentioned transparency into PBM pricing and other policies that would be required under several pieces of legislation being considered
by Congress. “We’re watching those policy changes very closely to monitor them and hopefully to bring more information and more updates to our audience,” she said.

Bioc said that he feels that patient is often not considered due to policies that are designed to meet the business needs of payers, providers, PBMs and manufacturers. Right now, the net price of biosimilars is changing, but patients have been experiencingextremely high prices. Education, he Bioc added, is the key to aligning the incentives of all parties involved. He stated that sometimes, “we do not understand the other players.”

“At the end of the day, we all have something to gain here with biosimilars, and looking at the [Humira] market, in particular, time is money,” Bioc said. “It’s money for everyone — for patients, for payers, for providers and IDNs [integrated delivery networks] and pharmacies. It’s not something that we can continue to wait on.”

Cancer’s reign over the drug development pipeline continues

There have exceptions to their rule, such as glucagon-like peptide 1 (GLP-1) drugs and the COVID-19 vaccines. But drugs to treat cancer have been the dominant force in pharmaceutical innovation, clinical trials and drug expenditures for many years now, and nothing in Kaelyn C. Boss’ oncology drug pipeline talk at the AMCP Nexus meeting.

Oncology represents a large portion of the drugs in development, with approximately 1,600 medicines and vaccines in the pipeline, Boss, a clinical consultant pharmacist at UMass Chan Medical School in Worcester, Massachusetts, told the AMCP Nexus audience. A large percentage of the cancer-fighting agents are treatments for rare cancers with a relatively small number of suitable patients, Boss said. But there are also a large number of agents in development for solid tumors that affect many more people, she noted. Boss said that spending on cancer drugs worldwide is projected to increase to $409 billion by 2028. The price of novel agents is high, at more than $200,000 per year on average. She said that biosimilars and generic medications may yield savings, but the money saved is no match for the trajectory of escalating spending.

Boss’ encyclopedic overview of oncology drug development included drugs that the FDA has approved this year, some of which were for new indications of previously approved drugs, as well those that haven’t been approved but with FDA action expected later this year or in early 2025.

Sita Bhatt, Pharm.D., a clinical pharmacy specialist at Boston Medical Center, joined Boss in making a presentation during the oncology pipeline session. She spoke about the growing number of cell therapies for solid tumors, a group that that includes LN-145-S1 for head and neck squamous cell carcinoma (HNSCC) and melanoma; LN-145 Gen 3 for HNSCC, melanoma and non-small cell lung cancer (NSCLC); letetresgene autoleucel for soft-tissue sarcoma; ECT240 for liver cancer; ET140203 for liver cancer; and CARv3-TEAM-E for glioblastoma.

“We can see a shift toward cell therapies for solid tumors,” Bhatt said, adding that “44% of all trials initiated in 2023 [were] for solid tumor indications. This is really where we’re seeing the trend in the oncology space right now.”

Here are some of the cancer drugs that Boss discussed that have been approved by the FDA this year.

Itovebi (inavolisib), a PI3K inhibitor for HER2-negative breast cancer with a PIK3CA mutation, wasapproved on Oct. 10. It was studied in combination with fulvestrant and palbociclib following progression on at least one endocrine-based regimen or within 12 months of adjuvant therapy. It is also being studied in combination with fulvestrant for HR+/HER2- breast cancer and in combination with dual HER2 blockade and endocrine therapy

Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs) is a PDL-1 inhibitor that was approved on Sept. 12 for multiple indications, including NSCLC. It is a formulation of Tecentriq that will allow for subcutaneous administration. Tecentriq was originally approved in 2016.

The combination of Lazcluze(lazertinib) and Rybrevant (amivantamab) was approved on Aug. 19 as a first-line treatment NSCLC with EGFR mutations.

Voranigo (vorasidenib) is an IDH1 and IDH2 inhibitor that was approved on Aug. 6 for treatment of grade 2 IDH-mutant glioma. The drug is also being studied in combination with Keytruda (pembrolizumab) for recurrent or persistent IDH-1 astrocytomas.

Tecelra (afamitresgene autoleucel) is a MAGE-A4-directed genetically modified autologous T-cell immunotherapy that received accelerated approval on
Aug. 2 as a treatment for unresectable or metastatic synovial sarcoma. It is one-time intravenous therapy that modifies T cells to attack cancer cells. Tecelra is the first T-cell receptor (TCR) therapy for cancer that the FDA has approved. The approval is limited to patients whose tumors test positive for the presence of MAGE-A4 The drug was launched at a list
price of $727,000.

Rytelo (imetelstat) is an oligonucleotide telomerase inhibitor that received approval on June 6 as a treatment for low- to intermediate-1 risk myelodysplastic syndrome with transfusion-dependent anemia. Rytelo is priced to cost approximately $385,000 a year (based on a patient weighing 70 kg), which is almost four times more than an Institute for Clinical and Economic Review assessment said it should cost based on common cost-effectiveness thresholds. Rytelo is the first telomerase inhibitor approved by the FDA.

And here are the cancer drugs mentioned by Boss that are likely to be coming up for FDA approval decisions soon.
A decision on zenocutuzumab, a bispecific antibody for NRG1-positive NSCLC and NRG1-positive pancreatic cancer, is expected in the fourth quarter of 2024.

A decision on obecabtagene autoleucel, a CAR-T therapy for relapsed or refractory adult B-cell acute lymphoblastic leukemia, is expected on Nov. 16. If the FDA approves it, obecabtagene autoleucel would be the third CAR-T treatment for this disease.

A decision on zanidatamab, a HER2-targeted bispecific antibody for previously treated, unresectable, locally advanced, or metastatic HER2-amplified biliary tract cancer, is expected on Nov. 29.

A decision on cosibelimab, a PD-L1 inhibitor that is a treatment for metastatic or locally advanced cutaneous squamous cell carcinoma, is expected on Dec. 28.