Can high-cost gene therapies become affordable for all?

A new generation of gene therapies offers hope for rare diseases but raises concerns about affordability. Health systems across the world are grappling with how to balance innovation with sustainability.

The impact of drugs like Zolgensma on children with spinal muscular atrophy can be transformative. Photo: Ryan Johnson

Four-year-old Edward Willis is a chatty child who is excited to go to nursery every day. Although he needs assistance with walking, he is making good progress. Working towards this milestone might seem unremarkable, but his development has been nothing short of a miracle for his parents, Megan and John, who live in London.

Edward was born with spinal muscular atrophy, a rare genetic disease that is correlated with insufficient levels of the survival motor neuron protein, which is vital for muscle development. It results in progressive muscle weakness, including weakness of the shoulders, hips, thighs, and upper back. Unfortunately, Edward has the most severe form of spinal muscular atrophy, which causes babies to lose control of all their muscles. They often die before the age of two from breathing difficulties.

Edward’s condition was rapidly deteriorating just as Zolgensma, a one-off gene therapy infusion treatment that could stop his condition progressing, became authorised in the EU. The problem was that it was not approved for use in the UK’s National Health Service (NHS). The list price in 2021 was £1.8 million (US$2.3 million)—reported at the time to be the most expensive drug in the world.

The Willis family and their friends began desperately crowdfunding to raise the money for treatment. Thankfully, the infusion was approved a few months later in March 2021 by the National Institute for Health and Care Excellence (NICE), despite the price tag (although a discount is believed to have been negotiated by NHS England).

The impact of the drug was transformative. “A week after he had the infusion [at 10 months old], Edward was babbling and sitting up—things we had been led to believe just wouldn’t happen for him,” Megan says. “We’re looking forward to him starting school and he is beginning to be able to walk unaided. The drug treatment gave him a future—without it he wouldn’t be here.”

The Willis family’s story illustrates an increasingly pressing dilemma for health systems across the world: how to allow access to revolutionary new treatments for rare diseases without compromising the health systems that foot the multi-million-dollar bills.

Tackling the affordability question

More than 60 gene therapy treatments for a range of diseases—made using techniques that modify a person’s genes to treat or cure disease—are expected to become available by 2030, up from 32 in April 2024. Thanks partly to incentives from governments for investment in rare diseases, such as longer exclusivity deals, tax breaks, and clinical research subsidies, many of these gene therapies are expected to benefit the treatment of people with rare diseases.

“The economics of it mean that the costs of developing these drugs for small numbers of patients are going to be high—it's specialty medicine.”

While undoubtedly good news for those affected by rare diseases, there are concerns about the affordability of these transformative drugs, even in high-income countries. A 2022 paper published by the US Institute for Clinical and Economic Review highlighted the fact that the average annual cost of an “orphan” treatment—medication specifically for rare diseases, developed to meet public health need rather than for economic reasons—was US$32,000 in 2019, with treatments ranging from less than US$6,000 to over US$50,000.

“The economics of it mean that the costs of developing these drugs for small numbers of patients are going to be high—it’s specialty medicine,” explains Brendan Shaw, a former assistant director general at IFPMA and principal at Shawview Consulting, an Australia-based advisory firm with a focus on the health and pharmaceutical sectors.

In resource-constrained health systems, the balancing act is especially delicate. Olivier Wouters, professor of health policy at Brown University in the US, says: “The first point to consider when it comes to gene therapies is whether they offer value for money at these high prices. The long-term efficacy and safety of some of these therapies remain uncertain. It might make good sense in some cases to prioritise other medicines, particularly in regions that still lack access to the most basic medicine.”

Wouters stresses though that beyond cost, low- and middle-income countries (LMICs) face additional barriers to accessing gene therapy. “Some [therapies] require specialised administration and infrastructure—it’s very different to just taking a pill,” he says.

High cost of rare diseases drugs

The most expensive drug in the world currently is reported to be Lenmeldy, a one-time gene therapy near-curative treatment for a rare genetic condition called metachromatic leukodystrophy, which causes the brain and nervous system to progressively lose function. Its reported list price is US$4.25 million in the US, US$2.4 million in Germany, and US$3.1 million in the UK.

“The main argument put forward is that the higher price reflects the fact some of the new treatments may represent possible ‘cures’ that will save healthcare systems money in the long run.”

Other high-cost drugs in the US include Beqvez and Hemgenix, gene therapy treatments for the blood clotting disorder haemophilia B. Beqvez and Hemgenix were reported to be US$3.5 million for one-time infusions. These are closely followed by Elevidys (a treatment for Duchenne muscular dystrophy) at US$3.2 million, and Lyfgenia (a treatment for sickle cell disease) at US$3.1 million.

“The main argument put forward is that the higher price reflects the fact some of the new treatments may represent possible ‘cures’ that will save healthcare systems money in the long run,” explains Susanne Michel. Michel is the vice president of market access, health technology, and evidence at Clinigen, an international specialist pharmaceutical services company that advises pharmaceutical and biopharmaceutical companies in different global markets, based in Germany.

“A drug may cost US$1.6 million but could be more cost-effective in the long run if it cures a genetic condition and saves a lifetime of ongoing hospital and drug costs. The difficulty is that this is uncertain at the time of the drug launch as typically drugs for rare diseases don’t have large numbers of patients in their trials,” she adds.

A spokesperson for Novartis, which manufactures Zolgensma—the spinal muscular atrophy treatment Edward received in the UK—says: “While a one-time gene therapy has a high unit price compared to conventional medicine, the full cost of Zolgensma medicine is incurred at the single point of administration and the beneficial effects are designed to be lifelong.”

Shaw says that it is important to examine the cost of gene therapies for rare diseases in the broader context of their potential value to society. “What is the benefit to society of a child with a rare disease who is ‘cured’ who goes on to have a normal, healthy life and build businesses, earn an income, pay taxes, and have a family?” he says.

Strategies to fund rare diseases drugs

It is not a given that the cost of multi-million-dollar drugs for rare diseases will be covered by health systems, even in high-income countries. For example, bluebird bio Inc. withdrew Zynteglo, a genomic treatment for beta thalassemia (an inherited blood disorder), from the European market after failing to agree on a price with authorities.

There is no international fund for very expensive gene therapy drugs, which means many LMICs cannot facilitate access. Michel says drugs for very rare conditions are sometimes made available “on a compassionate use basis or as part of a clinical trial”.

“Another thing that happens with some drugs is that they will be funded in [higher-income] countries in the region such as Saudia Arabia or the United Arab Emirates and then patients from a [lower-income] country nearby such as Egypt will be allowed access to them, sometimes [with patients] travelling to that regional centre for treatment,” she adds.

Michel says risk-sharing schemes are also negotiated, where health systems only pay if the person responds to the drug. If they do not, the pharmaceutical company bears the cost. In other cases, she explains, health systems pay for drugs in installments over several years.

Shaw says health systems have not traditionally been well set up to facilitate access to advanced treatments like gene therapies, but strategies like risk-sharing arrangements and pay-for-performance schemes can help address these challenges.

“A lot of the debate that is happening internationally at the moment is about how health systems can evolve to deal with these therapies as they’re coming through,” he says. “There are innovative pricing and evidence models that are starting to be talked about and experimented with in different ways.”

The Novartis spokesperson says Zolgensma is now approved in 58 countries, including Brazil and Argentina. “Novartis is committed to helping ensure that our medicines are accessible to as many eligible patients as possible, and we aim to be part of the solution on pricing and access to medicines by considering both effective affordability strategies and innovative solutions to disease management,” says the spokesperson. They explained that Novartis ranked number one in the 2024 Access to Medicine Index, “highlighting the company’s efforts in improving access to medicines around the world”.

Negotiating drug prices in Brazil

People with rare diseases have begun to gain access to gene therapy drugs in middle-income countries like Brazil, but is not without controversy, explains Professor Marisa Santos, an epidemiologist, infectious diseases specialist, and health technology assessor at Conitec (Committee for Health Technology Assessment). Conitec assesses the clinical efficacy, safety, budget impact, and cost effectiveness of new drugs; it also advises the Brazilian government on reimbursement.

Brazilians have access to healthcare through the Sistema Único de Saúde, the country’s unified public healthcare system, she explains. Around 25% of the population also pays for private sector cover. “The Ministry of Health’s strategy is to negotiate better drug prices and work with risk-sharing agreements with pharmaceutical companies, but it faces some legal barriers,” Santos says.

“Some of these new gene therapies cost millions of dollars for a potentially curative treatment, but we don’t know for sure if their effects are permanent or not.”

For example, the Supreme Court ruled in late January 2025 that patients with Duchenne muscular dystrophy should have right of access to Elevidys (US$3.2 million for a one-off dose, reimbursed by the government). “Conitec had not even reviewed it so it can effectively be bypassed by the courts. Patients can sue the government for reimbursement,” Santos says, explaining that all drugs are normally reviewed by Conitec but legal precedent, such as that set in the Elevidys case, means that the review can be bypassed by the courts and the government must provide the drug to patients.

She says the Supreme Court’s decision follows more than 100 successful lawsuits from families that effectively forced the Brazilian public health system to fund Zolgensma in 2023 without it being reviewed by Conitec first.

People with rare diseases have begun to gain access to gene therapy drugs in Brazil. Photo: Pan American Health Organization.

There are now worries that access to gene therapies will not be sustainable. “Some of these new gene therapies cost millions of dollars for a potentially curative treatment, but we don’t know for sure if their effects are permanent or not. We really need 20 years’ data to be sure these diseases will not come back, and we do not have it yet,” Santos says.

The Novartis spokesperson says the company “conducted extensive negotiations with the Brazilian federal government to determine a fair price [for Zolgensma] that would reflect both the country’s economic reality and the nature of the therapy”.

Santos worries that the introduction of many new gene therapies “could potentially cause the healthcare system to collapse”. “There won’t be enough money for other priorities such as infectious diseases and chronic diseases, which affect more people,” she says.

“We need to able to negotiate on price before reimbursement is agreed, and there needs to be risk-sharing because we don’t have long-term data on effectiveness [of gene therapies].”

Gene therapies remain unaffordable

Casgevy is another innovative new gene therapy treatment—for sickle cell disease, a group of inherited health conditions that affect the red blood cells. But the US$2.2 million it costs means it is unlikely to be made available in countries where most people with sickle cell disease live.

A 2015 study reported that about 90% of the world’s sickle cell disease population lives in Nigeria, India, and the Democratic Republic of the Congo, where the disease affects up to 2% of the population. In Nigeria, where most people pay out-of-pocket for drugs, expensive gene therapies remain out of reach, explains Professor Henry Okeri, deputy president (south) of the Pharmaceutical Society of Nigeria.

“The nature of the complex equipment, expert personnel, and regulatory frameworks needed to develop, test, and administer modern medicines like gene therapies are largely insufficient or absent; therefore, the majority of the population cannot access these modern medicines,” he says.

The situation highlights not only the stark disparities in access to potentially life-saving treatments for rare diseases, but also the pressing need for healthcare reform and new funding solutions. While new, expensive gene therapy treatments represent a remarkable advancement in medical science, their high costs remain a prohibitive barrier to access for many.

Shaw says the World Health Organization (WHO) Rare Disease Resolution advancing to a vote at the World Health Assembly in May offers an important opportunity for stakeholders to work together to implement solutions. “We need to find ways to make these treatments available for different types of health systems and find collaborative solutions across different sectors to ultimately make these treatments accessible to people around the world,” he concludes.