Rare disease patients face potential lack of access to gene therapies

300 million people living with rare diseases worldwide should have rights to the latest technologies

More gene therapies than ever are nearing maturity, and they promise to transform the lives of people with rare diseases. They won’t do anyone any good, however, if patients can’t access them.

Companies must do their part to make gene therapies accessible by practicing price discipline and investing heavily in next-generation technologies that will ultimately lower costs. But gene therapy developers alone can’t solve the access problem. Together with regulators, payers, non-profits and public institutions, all have roles to play in creating the business case for the many rare and ultra-rare diseases that lack treatments but could benefit from gene therapy.

The U.S. and European governments, through adoption of orphan drug laws, provide biopharmaceutical companies with economic incentives to create new medicines, such as gene therapies, for rare diseases whose small patient populations represent a low potential return on investment.

This public support, which includes tax credits, research grants and extended market exclusivity, creates an orphan disease business model that also rewards companies with higher prices to help offset their considerable R&D costs.

In a cruel twist of irony, however, sufferers of rare diseases, who number 300 million worldwide, now face the possibility they won’t be able to access gene therapies that have been in development for decades and are finally emerging as effective treatments.

The situation is significantly more dire for children with ultra-rare diseases, which account for 85% of all rare diseases. These patient populations are so small that even orphan drug laws don’t provide enough support for biopharmaceutical companies to invest in clinical development and commercial production. For ultra-rare diseases a new kind of economic model is required.

The first gene therapies have price tags ranging from several hundred thousand dollars to nearly $3 million. Companies that own these products justify the high prices by a combination of arguments: cost of development; cost of production, as gene therapies are probably the most complex products to manufacture; and unprecedented, potentially curative, therapeutic effects with a single treatment. While no one doubts they offer unprecedented therapeutic effect, if the high prices claimed by the initial gene therapy approvals set the standard, they will constitute a de facto obstacle to making gene therapies available to all patients who need them.

This is how a U.S. biotech company, which won approval in Europe for two gene therapies targeting rare diseases, based on technologies developed in Europe, and supported by orphan drug designations, was unable to reach agreement on pricing. It decided to withdraw both of its gene therapies from the European market, leaving patients of these diseases with no access to the medicines. This is unacceptable.

So how can governments, payers and drug developers overcome pricing issues and ensure all patients reap the rewards of gene therapy?

There are at least four types of solutions to consider, and some form of all of them will likely be needed.

The first is for drug developers, other biotechs and contract manufacturers to invest ambitiously in innovation to develop new vectors and other technologies with a goal of producing large quantities of gene therapy products at lower costs and more quickly. Manufacturing clearly is a key limiting factor for patient access.

All stakeholders, in particular drug developers, must agree to keep the prices for the end payer at a reasonable level, meaning a price that is affordable to payers and does not discourage them or jeopardize patient access.

The third type of solution is regulatory. Regulators can help optimize development costs for gene therapies by defining a set of standards for clinical trials and product registration.

Finally, for all the ultra-rare pathologies that have no commercial model, creative initiatives between pharma companies, not for-profit organizations and public institutions are needed to carry the weight of development and bring those drugs to patients. The Bespoke Gene Therapy Consortium in the U.S., which brings together private and public actors, is an interesting attempt to address many of these challenges. We can only hope other similar initiatives will be developed at the international level.

U.S. and European governments, long ago, decided people with rare diseases have as much right to innovative research and development as people with more common diseases. In December 2021, the United Nations General Assembly confirmed this commitment when it adopted a first-ever resolution urging all member states to recognize “the need to promote and protect the human rights of all persons, including the estimated 300 million persons living with rare diseases worldwide, many of whom are children.”

To achieve such a vision will require balancing the interests of drug developers and payers (public and private) with those of patients. Any solution, certainly, should include a willingness to pay private industry for its efforts. But in return for public contribution, there should be consideration for price discipline.

It also should be obvious that the technological and methodological advances made with gene therapies for rare diseases, in the long run, will benefit the broader population and the biopharmaceutical industry. Although much of the focus has been on rare diseases, gene therapy treatments already are available for more frequent diseases, in particular blood cancers, and their applications eventually will broaden.

Doing the work today that’s needed to make gene therapies accessible for rare disease patients, will help usher in an era in which the therapeutic modality can benefit patients with any disease, no matter how common and rare.

Frédéric Revah is CEO of Généthon, a not-for-profit laboratory based in France that is developing a pipeline of gene therapies for rare diseases.