Denise Myshko is your editorial contact for the Formulary Watch. She joined Formulary Watch as editor is June 2021 from Oncology Live. Prior to that, she was managing editor of PharmaVOICE, a trade publication in the pharmaceutical industry. Email: dmyshko@mjhlifesciences.com

Denise Myshko

Humana has updated its Medicare Advantage and Medicare Part D offerings for 2023. Drug benefits offered through Medicare Advantage include several new features, including $0 prescription copays on all covered Part D prescriptions in the Dual Eligible Special Needs Plans (D-SNPs) and $0 vaccines, including the shingles vaccine, while COVID-19 and flu vaccines will remain covered at $0. Member cost share of covered Part D insulin will be no more than $35 for every one-month (up to a 30-day) supply.

Additionally, Humana Medicare Advantage plans are removing the preferred retail pharmacy pricing to create one retail network with more than 60,000 pharmacies that will offer the same access to prescription drugs. Many plans include low-to-no cost sharing for commonly used generics and maintenance medications.

In Medicare Part D Prescription Drug Plans, updates will include $0 copays for many commonly prescribed medications and a network of retail and mail-order pharmacies that offer preferred cost-sharing, including Walmart, Sam’s Club and several grocery chains. In addition, covered vaccines will be offered at $0 copay and covered insulins at no more than $35 for every one-month (up to a 30-day) supply. In partnership with Walmart, Humana will continue to offer the Humana Walmart Value Rx plan that features affordable copays and access to a preferred cost-sharing network.

Additionally, the insurer has updated Humana Premier Rx with Improvements in coverage and benefits, such as 3,700 medications covered on the formulary, including 900 medications covered on tier 1 & tier 2 (with a $0 deductible); select insulins as low as $20; and gap coverage for tier 1 and tier 2 medications.

“We conducted extensive research to ensure our changes align with consumer wants and needs,” George Renaudin, Medicare president for Humana, said in a press release. “This research resulted in investments focused on what consumers want, like dental coverage, which is consistently a #1 priority in supplemental benefits for our members.”

The company indicated that it designed its plans for 2023 to ensure benefit stability or improvement for current Humana members. Humana will also expand Medicare HMO offerings into 260 new counties and introduce Medicare Local Preferred Provider Organization (LPPO) plans in 260 new counties. For the first time, LPPO plans will be available in California, Rhode Island and Wyoming, and D-SNPs are being added in South Dakota, Wisconsin and Wyoming.

Additionally, Veteran-focused plans will add prescription drugs and givebacks. Humana and USAA partnered to design the new Humana USAA Honor with Rx plan. It is designed to give veterans more flexibility to choose between the VA or civilian doctors, pharmacies and specialists. Benefits include $0 premiums, Part B giveback ranging from $40 to $75 a month depending on the plan, preventive dental coverage with an additional $1,000 allowance, and prescription drug options that offer access to medications at local pharmacies with co-pays as low as $0.

Annual enrollment for Medicare begins Oct. 15, 2022, and continues through Dec. 7, 2022.

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Humana’s 2023 Medicare pharmacy benefits updates include $0 copays, simplified access to prescriptions and Veteran’s focused-plans that add pharmacy benefits.

Humana Updates Medicare Pharmacy Benefits

 a biologics license application (BLA) to the FDA for its investigational adeno-associated virus vector gene therapy, valoctocogene roxaparvovec, for adults with severe hemophilia A.

The resubmission incorporates the company’s response to the FDA complete response letter for valoctocogene roxaparvovec gene therapy issued on Aug. 18, 2020, including two-year outcomes from the global GENEr8-1 phase 3 study and supportive data from five years of follow-up from the ongoing phase 1/2 dose escalation study.

BioMarin anticipates an FDA response by the end of October on whether the BLA resubmission is complete and acceptable for review. Typically, BLA resubmissions are followed by a six-month review procedure. However, company executives anticipate an additional three months of review. If approved, valoctocogene roxaparvovec would be the first commercially-available gene therapy in the United States for the treatment of severe hemophilia A.

“This large and robust data set provided in this BLA resubmission shows an encouraging efficacy profile,” Hank Fuchs, M.D., president of worldwide research and development at BioMarin, said in a press release. “We remain committed to sharing these data with the public, along with even longer-term data generated through our ongoing clinical trials and any post-approval studies, to further our understanding of AAV gene therapy in severe hemophilia A and of gene therapies more broadly.”

Hemophilia A is a genetic disease caused by the deficiency of clotting factor VIII. It is the most common type of hemophilia and occurs much more frequently in males; incidence is estimated at 1 in 4,000-5,000 male births. The current standard of care for most hemophilia A patients who are severely affected today is a prophylactic regimen of intravenous infusions three times per week.

BioMarin’s gene therapy uses an adeno-associated virus vector to deliver a functional gene to the cells in the liver that is designed to enable the body to produce Factor VIII on its own without the need for continued hemophilia prophylaxis.

In the phase 1/2 study, the safety profile of valoctocogene roxaparvovec was consistent with previously reported data with no delayed-onset treatment related adverse events. All participants continue to remain off corticosteroids since the first year. No participants developed inhibitors to Factor VIII, and no participants withdrew from the study.No participants have developed thrombotic events.

The most common adverse occurred early after a single infusion and included short-lived infusion-associated reactions and transient, asymptomatic, and mild to moderate rise in the levels of certain proteins and enzymes measured in liver function tests with no long-lasting clinical sequelae.

, the Institute for Clinical and Economic Review (ICER) found that valoctocogene roxaparvovec at an assumed placeholder price of $2.5 million would provide cost savings and projected gains in quality adjusted life years. The draft evidence report is now open for public comment, with a final report expected near the end of the year.

ICER calculated the lifetime cost of managing hemophilia A among clinically eligible patients using one-time administration with valoctocogene roxaparvovec versus emicizumab prophylaxis. Total costs in the model include treatment, treatment-related adverse events, treatment for bleeding episodes, arthropathy, surgery, and non-drug costs. ICER assumed annual cost of emicizumab to be $640,000 per year and one-time valoctocogene roxaparvovec price to be $2.5 million.

The European Commission granted conditional marketing authorization to valoctocogene roxaparvovec gene therapy under the brand name Roctavian on Aug. 24, 2022, and endorsed the recommendation from the European Medicines Agency (EMA) to maintain orphan drug designation, thereby granting a 10-year period of market exclusivity in the European Union.


If approved, valoctocogene roxaparvovec would be the first commercially-available gene therapy in the United States for the treatment of severe hemophilia A.


BioMarin Resubmits BLA for Hemophilia A Gene Therapy

 Amylyx Pharmaceuticals’ AMX0035 — now with the brand name Relyvrio (sodium phenylbutyrate/taurursodiol) — to treat patients with amyotrophic lateral sclerosis (ALS). It is an oral, fixed-dose combination therapy that should be available within four to six weeks, the company said in a call with investors. It will be available through specialty pharmacies, and can be used as a monotherapy or with other therapies.

ALS is a rare disease that attacks and kills the nerve cells that control voluntary muscles. It is a progressive disease, and most cases will result in death from respiratory failure, usually within three to five years from when the symptoms first appear. About 5,000 people in the United States are diagnosed with ALS annually and about 29,000 people are currently living with ALS.

“The approval of a new treatment that helps slow the progression of ALS, preserve physical function and potentially extend survival has the potential to greatly impact the hundreds of people living with ALS who I currently treat,” Merit Cudkowicz, M.D., co-principal investigator of the CENTAUR trial, said in a 

. “There are too few options to target this uniformly fatal and rapid illness, and I am encouraged at this outcome and what it represents for my patients and their families.”

Cudkowica is co-founder of the Northeast ALS Consortium, chief of Neurology and the director of the Healey & AMG Center for ALS and chief of Neurology at Massachusetts General Hospital, and the Julieanne Dorn Professor of Neurology at Harvard Medical School.

The company formed the Amylyx Care Team, which will provide a single point of contact for patients and help with financial assistance. The wholesale acquisition cost will be $158,000 per year for the first year, which company officials said is below the last approved ALS therapy. Mitsubishi Tanabe Pharma’s Radicava (edaravone), which was approved in 2017, costs about $171,000 a year.

 from the Institute for Clinical and Economic Review, the therapy would only achieve traditional thresholds of cost-effectiveness if priced between $9,100 to $30,700 per year.

The company indicated in its investor call that copays for patients in commercial plans will be zero and Relyvrio will be available at no cost to those who are uninsured or underinsured. Patients who participated in clinical trials will have continued access to Relyvrio.

The approval of Relyvrio is based on data from CENTAUR, a multicenter phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized, placebo-controlled phase and an open-label extension long-term follow-up phase. The most common adverse events occurring were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first three weeks of treatment.

Related: FDA Advisory Committee Supports Approval of AMX0035 for ALS

Earlier this month, an FDA advisory voted to support approval of the therapy in a 7 to 2 vote, reversing an earlier vote against Relyvrio. At the first advisory committee meeting in March 2022 six of the 10 members voted no on the question of whether the open-label extension of the phase 2 CENTAUR trial established a conclusion that AMX0035 is effective in the treatment of patients with ALS.

Amylyx had submitted additional analysis of survival data from the CENTAUR study and its open-label extension, along with biomarker results from a recently completed phase 2 study of AMX0035 in Alzheimer’s disease. The data in part held to sway several committee members to switch their votes from no to yes.

Research of Relyvrio continues with the phase 3 PHOENIX

, with results expected in 2024. This trial expects to enroll 600 patients and compare Relyvrio versus placebo. The primary efficacy outcome is the composite measure of survival and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score progression over 48 weeks and survival and tolerability over 48 weeks.

The therapy was also approved in Canada in June with the brand name Albrioza. The company also expects a potential decision from EMA the first half of 2023.

Now with the brand name Relyvrio, the new therapy should be available within four to six weeks. It will have a wholesale acquisition cost of $158,000 per year.

FDA Approves Amylyx’s ALS Therapy

Previously rare in oncology, formulary exclusions are becoming a way for national insurers and PBMs to have some control over oncology drug expenditures, finds a new 

 from IQVIA. From 2021 to 2022, there was a 40% growth in the use of exclusions where a generic or biosimilar is preferred. In 2022, the seven top national payers and PBMs have a combined 94 oncology exclusions, 34 of which have only brands for preferred alternatives.

“With the impact of COVID-19 (and now long COVID), payers are seeking innovative ways to help with cash flow and reduce financial risks,” Jing Yang, principal, IQVIA US Market Access Strategy Consulting told 

. “As more treatment options become available and as the treatment paradigm for certain tumor types shifts from ‘acute’ to ‘chronic disease management, payers will continue to look for ways to minimize longer term budget impact, with the utilization of formulary exclusion being one of them.”

With new product approvals and existing product label extensions, payers, especially national payers, continue to expand their use of formulary exclusions with no sign of slowing down the oncology formulary control, Yang said.

The overall cost burden of oncology – particularly as many patients live with cancer and manage it like a chronic condition – is only expected to grow. “Americans are getting older, and that brings a growing demand for healthcare, including cancer medicines,” she said. “Payers will look to mitigate costs and achieve better cost-effectiveness where they can, and managed formularies may help them extract higher rebates as well as manage utilization.”

IQVIA’s analysis follows research by others that shows formulary exclusions across therapeutic areas are increasing. Xcenda earlier this year released an analysis of the three largest PBMs — CVS Caremark, Express Scripts, and OptumRx. This analysis finds the largest PBMs excluding medicines in classes where generics are not available or for serious conditions, such as oncology and autoimmune disorders.

Related:PBM Exclusions Increasing, Finds New Analysis

IQVIA’s analysis find that oncology formulary exclusions continue to be most common in tumor types where competition is greatest, such as breast cancer, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. Additionally, several branded medicines that faced biosimilars in 2019 are only just now seeing their first formulary exclusions at the national level. These include three products from Genentech: Avastin (bevacizumab), Rituxan (rituximab), and Herceptin (trastuzumab).

But researchers said that exclusions don’t necessarily mean patients have to use less appropriate treatment. They found that 96% of exclusion were in favor of preferred alternatives that had the same National Comprehensive Cancer Network (NCCN) clinical rating as the excluded brand. “For patients, the exclusions will unlikely significantly disrupt the overall treatment,” Yang said. “Additionally, the system may benefit from reduced cost alternatives. However, formulary exclusions may make patients feel that fewer options are available, even though there are other options that can achieve similar outcomes.”

Jing Yang from IQVIA discusses how national payers are using formulary exclusions for oncology therapeutics.

IQVIA: Payers Increase Exclusions for Oncology Drugs

The COVID-19 pandemic has brought increased economic, physical, and psychological strain to many Americans and coincided with an increase in opioid overdose deaths, according to a recent study 

“The increase in opioid overdose deaths during the pandemic has been attributed to various factors: reduced access to interventions, increased levels of stress due to isolation and loss of mental health support, and changes in the types/combinations and purity of drugs and patterns of drug use,” Carl Black, pharmacist-in-charge at Optum Rx, told 

To address misuse of opioids, Optum Rx provides services and solutions that help prevent fraud, promote better prescribing accuracy, reduce drug errors, and align with state and federal pharmacy laws. “Our mission is to get out in front of misuse, abuse, dependence and medication sharing before it starts,” Black said.

Addressing opioid use and abuse has been a priority for many PBMs and health plans. For example, a pilot intervention program developed by Prime Therapeutics saw decreased opioid claims and lower morphine milligram equivalents for Medicare members who were at high risk of overusing opioids.

Related: Prime Therapeutics Reduces Opioid Claims with Targeted Intervention

Optum Rx’s Opioid Risk Management is a comprehensive solution for opioid management and prevention. Since 2018, Optum Rx’s opioid management program has resulted in a 62% reduction in total opioid quantity.

Optum Home Delivery implements specific requirements for opioid medications dispensed, including warning caps and labels, limiting quantities to a 30-day supply, and using an ePrescribing requirement. The home delivery program employs 1,200 pharmacists and pharmacy technicians on staff that are available 24/7.  The program was recently awarded the URAC Opioid Stewardship Designation for excellence in quality care for opioid prescriptions. It is the first accredited mail order pharmacy to earn this designation.

“What many people may not realize is that home delivery offers a far more intensive clinical management environment than the typical retail setting,” Black said. “Our consulting pharmacists spend 70% of their time with patients vs. 10% of time spent with patients in a retail setting. Home delivery members with chronic illness are more likely to be filling and taking long-term medications. Our average adherence was 20% higher with home delivery than for retail. This has shown to improve health outcomes and reduce other associated medical costs.”

Stemming the tide of opioid deaths means closely managing how much opioid is available to each patient, Black said. The current CDC guidelines approach this by promoting what are called “morphine-milligram” dosing equivalents (MMEs). This is a numerical standard that compares the relative potency of different opioid drugs, which in turn makes it easier to evaluate how much risk each patient faces.

Additionally, Black said Optum Rx has procedures in place that exceed state requirements for filling opioid prescriptions. Pharmacists and team members review patient profiles and history, such as taking more than three to five medications; prescriber practices and habits; and differing state mandates.

Optum, he said, is positioned to address this crisis by connecting efforts across the entire health system and continuum of care. “We start with preventing opioid misuse and addiction by educating care providers and individuals on the proper use of opioids, promoting alternative treatments for pain, advancing best practices for prescribing and using these highly addictive medications — and intervening when needed — in a way that protects the individual’s privacy,” he said. “We collaborate with providers to make sure individuals struggling with opioid use disorder are connected to evidenced-based treatment in their local communities and have personalized support for long-term recovery.”

Carl Black, pharmacist-in-charge at Optum Rx, talks about how the PBM has decreased dispensed opioids by 62% since 2018.

Optum’s Efforts Combat Opioid Misuse and Abuse

Health plans use updated evidence when revising their specialty drug coverage policies, but those updates tend to focus on health technology assessments, randomized clinical trials, and systematic reviews/meta-analyses and not real-world evidence studies and economic evaluations, according to a recent review 

Journal of Managed Care + Specialty Pharmacy

“The mismatch between the evidence developed by researchers and the evidence cited by health plans suggests that health plan officials may not find much of the available evidence to be of value when formulating coverage policies,” James D. Chambers, Ph.D., one of the authors of the paper told 

. “Going forward, we should aim for greater alignment. This may require product manufacturers to engage earlier, and more often, with health plans when developing evidence generation programs for their products.” Chambers is associate professor of medicines, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center in Boston.

Researchers at the Institute for Clinical Research and Health Policy Studies reviewed the citations of clinical and economic evidence plans included in their drug coverage policies between August 2017 and August 2019. They identified drug-indication pairs (e.g., infliximab for rheumatoid arthritis) and examined the frequency with which plans reissued these policies between these two time points and the frequency with which plans altered coverage criteria or updated the cited evidence.

Researchers selected 20 drug-indication pairs and they performed a literature search of PubMed to identify the evidence available, including randomized controlled trials, real-world evidence studies, other clinical studies, economic studies, technology assessments and treatment guidelines. They then compared the literature search with evidence cited in coverage policies.

They identified 4,597 coverage policies that plans made available in both August 2017 and August 2019, of which plans reissued 4,468 (97%). Of the reissued policies, 17% revised coverage criteria and 84% revised the evidence cited, and 15% of reissued policies revised both their coverage criteria and the evidence cited, 2% revised only their coverage criteria, and 69% revised only the cited evidence. A total of 14% of policies revised neither the coverage criteria nor the evidence cited.

For drugs approved no earlier than August 2014, plans cited randomized controlled trials and other clinical studies most comprehensively (7% and 5%, respectively); for drugs approved from August 2009 to August 2014, plans cited clinical guidelines and evidence synthesis studies most comprehensively (8% and 5%, respectively); and for drugs approved before August 2009, plans cited health technology assessments most comprehensively (4%).

“Our study indicates that the evidence cited in coverage policies evolves over a product’s life cycle. Plans tended to cite RCTs and other clinical studies for recently approved products and cite clinical treatment guidelines and evidence syntheses for products on the market for longer,” researchers wrote.

Researchers cited several limitations, including a reliance on health plans’ publicly available coverage policies. They said that plans may not fully report the evidence that they review. Additionally, the suggested that the study may not be generalizable to other U.S. commercial health plans or to public healthcare payers (e.g., Medicaid and Medicare). They also did not investigate how newly cited studies affected plan decision making.

This study was funded by the National Pharmaceutical Council.

But researchers found that only a small percentage of plans use available real-world evidence studies and economic evaluations in their coverage policies.
