With three recombinant adeno-associated virus (rAAV) gene therapies approved by the FDA and several more in the pipeline, payors will need strategies to cover these expensive treatments to ensure equitable access to care for appropriate patients, experts said at the AMCP 2023 annual meeting, in San Antonio.
The first step is to understand the basics of how gene therapy works and become familiar with approved treatments, noted Andy Killpack, PharmD, the director of specialty clinical solutions for Magellan Rx. He explained that gene therapy is used to modify or manipulate the expression of a gene, or to alter the biological properties of living cells for therapeutic use, by replacing, inactivating or adding a gene. Using rAAVs as a vector to deliver gene therapy has several benefits, Dr. Killpack noted: They do not elicit as strong an immune response or cause disease; can transport DNA to target cells; and can cross cell membranes to access areas such as the liver, lungs, retina, central nervous system and muscle cells. However, because of a limited ability to “package” or hold large strands of DNA, rAAV gene therapies have limited utility in conditions involving stem cells that divide rapidly (Mol Brain 2014;7:17). This limitation is one of their biggest drawbacks, Dr. Killpack said.
Currently, three rAAV gene therapies have been approved by the FDA, he said: voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics) for the treatment of adults with inherited retinal disease due to mutations in the RPE65 gene; onasemnogene abeparvovec (Zolgensma, Novartis) for the treatment of spinal muscular atrophy in pediatric patients under 2 years old with mutations in the SMN1 gene; and etranacogene dezaparvovec (Hemgenix, CSL Behring) for the treatment of hemophilia B with factor IX deficiency.
The inherited retinal disease affects an estimated 1,000 to 2,000 people, and is considered an ultrarare disease, Dr. Killpack said. Voretigene neparvovec delivers a normal copy of the gene encoding RPE65 directly to retinal cells. The most recent published data (Ophthalmology 2021;128[10]:1460-1468) showed that improvements in ambulatory navigation, light sensitivity and visual field were maintained for up to three to four years, he noted, adding that monitoring of patient outcomes is ongoing.
Spinal muscular atrophy affects one in every 10,000 births. Survival is one of the main efficacy endpoints used to assess therapy. Onasemnogene abeparvovec has been shown to help stop progression of disease, with efficacy seen in patients up to 6 years of age so far (JAMA Neurol 2021;78[7]:834-841), showing sustained durability, Dr. Killpack said. Patient monitoring is ongoing.
Hemophilia B occurs in approximately one in 25,000 male births. The efficacy of etranacogene dezaparvovec has been studied assessing annualized bleed episodes in months 7 to 18 after administration compared with a six-month lead-in period. Results of the HOPE-B extension trial show elevated and sustained mean factor IX activity levels and durable hemostatic protection at 24 months, with plans to continue to monitor patients for 15 years after administration, he said.
More Gene Therapies on Tap
There is a “very robust” pipeline of additional products, Dr. Killpack said. They include therapies for early-stage Duchenne muscular dystrophy, aromatic immunoenzyme deficiencies, hemophilia A, hemophilia B, optic neuropathy and Huntington’s disease. “With recombinant adeno-associated viral gene therapies being such a versatile viral vector, we’re certainly just at the tip of the iceberg when it comes to the number of these products being approved and on the market.”
However, there still are some limitations and unknowns, he noted. Because of the nature of viral vectors, they could elicit an immune response and limit the products’ effectiveness. It’s also unknown how long these therapies are durable. “Until there’s definitive evidence supporting long-term efficacy, this will always be considered a limiting factor,” Dr. Killpack said.
Balancing Cost and Clinical Outcomes
For payors, reimbursement may be the most pressing limitation. Gene therapies can be very expensive, but payors must consider that cost versus the total cost of care of long-term treatment for a rare disease, said Michelle Booth, PharmD, the senior director of specialty clinical solutions for Magellan Rx. “The therapies are thought of to be one-and-done, but we don’t know that for sure.” If a therapy doesn’t turn out to be a long-term fix, payors still will be responsible for covering the cost of the drug and patients are in the same situation as if they hadn’t received the therapy, she said.
There is no clear single solution to cover payments for the therapies, but managed care companies are considering a number of payment models, Dr. Booth said:
- Subscription payments. These are agreements between a payor or state and manufacturer in which the manufacturer will set a lower price for a therapy.
- Outcomes- or milestone-based agreements. These contracts between payors and manufacturers include how well the drug is working, either in the pricing or in the form of a rebate. Payors could be refunded if a therapy does not meet or maintain certain outcomes within a predetermined period; or if the drug does meet or exceed expectations, the payor will provide payment in full or a bonus payment.
- Annuity payments. This model spreads out payments over time. The payments follow the patient if they move from one insurance plan to another.
- Mortgage model. The “mortgage” allows payors to spread out payments over time. These payments do not follow the patient to another plan.
- High-risk patient pools. This method places people with preexisting health conditions into a disease management program with higher care coordination. Therapies are paid for by statutory health plans, or “sickness funds.”
- Reinsurance. This is an insurance plan for insurers to cover them for catastrophic loss such as an expensive gene therapy claim.
Noncoverage of Expensive Therapies
Alternatively, “a few employers already are considering not covering, or excluding, gene therapy as a benefit,” Erin Lopata, PharmD, MPH, the vice president and director of the access experience team at PrecisionValue, a market access company, told Specialty Pharmacy Continuum.
Another strategy that organizations are exploring is carving out gene therapy coverage, in which employers (or payors) pay a premium to a third-party firm to take on the financial risk and also provide related services, such as care coordination and post-treatment monitoring, said Dr. Lopata, who co-authored a recent article (J Manag Care Spec 2023;29[7]:782-790) looking at financial models for “high-investment” medications such as cell and gene therapies.
The carve-out approach can be confusing for patients who are used to receiving all healthcare coverage from one entity, she said. “There’s definitely the need for patient education around the benefits for payors or employers that choose to work with these third parties to support coverage of gene therapy.”
There has been more interest among both payors and employers in examining annuity or amortization-type models by which the costs of cell and gene therapies are spread out over time, Dr. Lopata added. Such models can be tied to patient outcomes, such as an outcomes-based annuity model, in which payors pay over time but the payments are linked to patients meeting certain milestones related to their response to therapy. “What we’re likely going to see is continued focus on outcomes and looking for ways to tie payment to relevant metrics while making the process operationally feasible for employers and payors,” she said.
‘Still All Very Theoretical’
“It was a great overview of a very hot topic,” commented Michelle Vu, PharmD, MPH, RPh, a senior researcher in value-based contracting and health economics and outcomes research at Optum Insight, who was in the AMCP session audience. “It’s still all very theoretical right now. When I saw the list of contracting payment strategies, I thought, ‘How many of these do we actually do?’ Payment has to happen in the same way that we’ve been paying for drugs. … But I really hope that maybe in a year or so we’ll have a lot more presentations that are drug-specific and large organization payor-specific instances of the challenges they ran into testing these out.
“We have to figure this out,” she added, “so that the patient gets access to the treatment.”
The sources reported no relevant financial disclosures.
This article is from the October 2023 print issue.