Considerations for a Pathway to Commercializing Gene Therapies for Ultra-rare Diseases

Think Global

Over 8000 genetic rare diseases have been identified globally, yet the current therapeutic landscape indicates that only 5% of these conditions currently have FDA-approved treatments^[1].

Over the last decade, many small biotech companies began developing new gene therapy-based treatments for ultra-rare diseases.

However, bringing these treatments to patients has been a significant challenge due to:

1. The high pre-clinical and clinical development costs
2. An inherent restriction to a single indication
3. Limited opportunity for label expansion post- commercialization

Where does this leave the remaining ultra-rare disease programs?

These confounding factors coalesce into negative net present value calculations that discourage many companies from continuing ultra-rare disease programs. Between 2021 and 2023, over fifty rare disease programs were either shelved or abandoned altogether^[2].

Climbing Out of the Ultra-rare Disease “Valley of Death”

First, let’s acknowledge the problem – the cash required to bring ultra-rate therapies through development phase has more recently been deployed elsewhere. This leads to the so-called cash flow “Valley of Death” in the development of ultra-rare disease gene therapies, as shown above. Traditional investment sources for gene therapy development and commercialization, such as Big Pharma and venture capital, are no longer as willing to find these programs as they have in past years. Patient groups, academia, and foundations can only do so much to fill the valley. But lest we forget, millions of real children, real adults, and real lives remain at stake with little to no treatment alternatives.

Where Does This Leave Us?

At TKD Solutions, we believe that a multifaceted approach will be required to climb out of this valley.

We will be writing a series of reports that bring forth opportunities for true collaboration across development, supply chain, CMC, and regulatory pathways to develop risk-appropriate approaches that will rein in costs, reduce development timelines, and establish more robust platform approaches that are specifically designed for ultra-rare disease programs.

Resources:

^[1] Berry, Diane et al, Ensuring patient access to gene therapies for rare diseases: Navigating reimbursement and coverage challenges, Molecular Therapy Methods & Clinical Development, Volume 33, Issue 1, 101403

^[2] Yingling N, Sena-Esteves M, Gray-Edwards HL. A Paradox of the Field’s Own Success: Unintended Challenges in Bringing Cutting-Edge Science from the Bench to the Market. Hum Gene Ther. 2024 Feb;35(3-4):83-88. doi: 10.1089/hum.2023.29264.nyi. PMID: 38381466.

^[3] Steinmetz, Karen & Edward, Spack. (2009). The basics of preclinical drug development for neurodegenerative disease indications. BMC Neurology. 9 Suppl 1. S2. 10.1186/1471-2377-9-S1-S2.