March 24, 2023
The introduction and advancement of gene therapy offers society and researchers a new way to treat genetic diseases by replacing or editing disease-causing genes. However, despite the promise, developing drugs for rare (and especially ultra-rare) diseases is a complex and expensive process. As gene therapy and gene editing technologies advance,the current models used to determine insurance coverage for therapeutics need to evolve in order to ensure access to treatment for even the rarest diseases.
With early academic and non-profit efforts to develop therapeutics for a small group or even individual patients, there is a rapidly growing need to figure out how to pay for these advancements without placing the burden squarely on the shoulders of patient families.
The underlying challenge of ultra-rare disease drug development and the flaw in the current models used to determine insurance coverage both stem from the same reality: small patient populations. With limited numbers of patients per disease (but paradoxically very large numbers in aggregate), the incumbent drug development and reimbursement system is designed for large numbers of patients. These large patient populations are needed to support well- powered clinical trials that provide the data for regulators and insurance companies to decide approval and reimbursement. But this model simply does not work for ultra-rare diseases.
For example, several of CRD’s programs are focused on ultra-rare mutations of Duchenne muscular dystrophy,including our exon 57-59 mutation program. Currently, we’ve identified no more than 25 other patients with this mutation. While there’s no cutoff for the specific number of patients needed to enable drug development, commercial drug developers typically need to have hundreds to thousands of patients impacted to even consider launching a program. Insurance companies also make the decision to cover a drug based on well-powered clinical trials, as well as commercialization approval (a BLA or NDA). Assuming an ultra-rare disease drug candidate attracts commercial interest, insurance reimbursement becomes the next roadblock as there may not be sufficient numbers of patients to conduct the full spectrum of clinical trials required for a BLA or NDA. Without insurance coverage, whether through public or private insurance companies, the cost burden then falls to families and their communities to fund.
Several mechanisms have recently been discussed as potential pathways for paying for development costs for rare disease drugs. These mechanisms include approaches such as, public-private partnerships, NIH mechanisms like the URGenT Program, and foundation funding.
While each are positive steps in the right direction, these solutions lack the speed of funding required when time is of the essence or the capital provided is too limited to effectively advance a therapeutic development program from bench to bedside.
When one analyzes the cost of a drug development program, a significant fraction of the cost is from manufacturing the clinical product and the administration of the drug. For instance, 80% of the cost of Cure Rare Disease’s first program was related to manufacturing the clinical grade product. Thus, if such a system existed wherein there was timely coverage of a clinical product and trial based on IND approval for a non-commercializable disease, this could offer a potentially equitable route for nonprofits, families and foundations to participate in gene therapy without creating an often insurmountable financial burden. This may be one potential avenue where the federal government can provide support.
In lieu of a clear pathway for ultra-rare disease financing, one approach that Cure Rare Disease is taking is the concept of licensing commercializable therapeutics in an effort to use that capital to enable the development of therapeutics that do not have commercial potential. By developing and then de-risking therapeutics through a Phase I/IIa clinical trial, we generate preclinical and clinical data in ideally sufficient quantities to then license the therapeutic to a larger partner who has the infrastructure capable to conduct the rest of clinical development and commercialization of the drug. In this case, patients benefit from being able to potentially participate in clinical trials or eventually take advantage of an approved therapeutic. Ultra-rare disease patients also benefit by having more capital available for drug development.
While there’s potentially numerous paths to solve for this challenge it is a challenge desperately needing a solution. Drug development for rare diseases is a challenging and expensive process. However, there may be ways to finance drug development costs and create more equity for ultra-rare disease patients including IND-approval based financing or reimbursement. With the support of the Muscular Dystrophy Association’s grant, we are beginning to study and develop sustainable solutions to tackle this problem and we look forward to widely sharing our findings once they are complete in the coming months.
Our research and development is powered by the generous financial support of families, rare disease communities and organizations unwilling to accept the status quo of drug development practices. As a 501c3 non-profit biotech, 93+% of all donations go directly to the research and development of life-saving therapies.
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