Rare Diseases: Once Lightning Strikes, Now Storms of Lightning | Asembia AXS25

Clinical efficacy, net price and safety continue to be top factors payers consider when making formulary decisions for treatments for rare diseases, said experts at a session at Asembia’s AXS25 Summit in Las Vegas.

Stephen Meninger, Pharm.D.

Financial factors, however, are playing an increasingly larger role in payer decision-making. “We’ve seen this uptick of financial pressure when it comes to decision-making for access decisions,” Stephen Meninger, Pharm.D., medical outcomes science liaison at Alnylam Pharmaceuticals Inc., said in an interview before the meeting. Alnylam is a pharmaceutical company that markets several products for rare diseases, including Onpattro (patisiran), Amvuttra (vutrisiran), Givlaari (givosiran) and Oxlumo (lumasiran). Alnylam’s products are small interfering RNA medications that work by degrading RNA to prevent the transcription of disease-causing DNA.

Increasing economic pressures have led many stakeholders to expand their use of cost-control measures, such as stricter prior authorization , specialty pharmacy and site-of-care mandates, and risk-sharing agreements, according to the most recent Rare Disease Trend Report by Alnylam, a survey of payers and employers on the management of rare disease products. The respondents, which included 30 U.S.-based medical and pharmacy directors and employers, completed the survey from Oct. 14, 2024, to Oct. 24, 2024.

Alnylam added employer groups to the survey this year. “In years past, employer groups have thought of rare diseases as lightning strikes. Now, they’re thinking about them more as lightning storms,” said Meninger. “Employers are more involved in that decision-making in their own formulary. They are more engaged.”

Costs for new treatments continue to rise. The median annual treatment cost of new drugs that launched in 2024 was more than $350,000, with treatments for cancer and rare diseases priced to cost more than $400,000 per patient, according to the April 2025 Use of Medicines report from IQVIA Institute for Human Data Science.

Traditionally, when new drugs enter the market, competition brings prices down. But Meninger said that is not always the case with specialty and rare disease therapies. Competition, he said, helps payers “navigate and control this rare disease space more like traditional disease spaces.”

About 7,000 rare diseases have been identified that impact about 25 million to 30 million Americans. Many of these diseases have a genetic cause.

The pressure on payers is likely to continue. In 2024, the FDA approved 50 novel drugs, with more than half for patients with rare or orphan diseases. The IQVIA Institute for Human Data Science projects similar trends in approval of rare disease drugs over the next few years, with cancer drugs and those for immune system-related diseases fueling the rise. Drug development in oncology alone is projected to add 100 new treatments over five years, contributing to an increase in spending of $224 billion to a total of more than $440 billion in 2028, according to IQVIA. Treatments for rare diseases accounted for 45% of new trial start-ups in 2024, according to another IQVIA report that was published earlier this year. Of those, 69% were for therapies for rare cancers. New trials in metabolic/endocrinology and infectious diseases remained essentially flat compared with 2023.

Respondents to the Alnylam survey indicated that value- and outcomes-based contracts are among the most innovative ways to manage the ballooning cost of drugs for rare diseases. Meninger says these contracts consider efficacy and safety, two of payers’ top concerns.

But outcomes-based agreements are difficult to execute, Jeffrey Dunn, president of the Cooperative Benefits Group and another panelist at the session, said in an interview. Cooperative Benefits Group is a pharmacy benefit manager (PBM) that creates joint venture partnerships with its clients

“There is a growing opportunity in the future [for outcomes-based agreements], if we could figure that out.”

But it’s hard to measure outcomes in these contracts unless they’re claim based, Dunn says. “If you offset the use of another expensive therapy, then there is value there. And if I pay for gene therapy and still have to pay for the older, expensive drug that it’s supposed to replace, then there should be some value in return. This is claims based and I can measure this.”

Dunn says Cooperative Benefits Group has several outcomes-based contracts with manufacturers for his clients. “But very little money goes back to clients. We're not getting money back from the pharmaceutical companies because there’s no way to get the data to actually follow through on them.”

Drugs to treat patients with depression, Dunn said, are an example of the difficulty in assessing outcomes. “What data do you need to pull to show somebody is not doing better? If this is tied to utilization, we can do this. But many of the outcomes-based contracts are just impossible to measure and collect data on.”

The same is true for outcomes agreements for oncology therapies, he says. “How do you prove that the cause of somebody progressing in cancer was due to the lack of efficacy of the drug? It could be due to other things — side effects, compliance, adherence,” he says.

Value-based agreements, on the other hand, Dunn said, are more likely to rely on claim data to assess outcomes relative to costs. For example, value-based agreements are often used to hedge risk for gene therapies, where payers can measure whether a gene therapy has resulted in the lowered use of another high-cost therapy.