The commentary titled ‘Establishing a Commercial Solution for Extremely Rare Genetic Diseases’ was published in Nature Biotechnology
Commentary coincides with draft guidance from the FDA outlining a framework to accelerate development of treatments for ultra-rare diseases
SAN DIEGO–(BUSINESS WIRE)–n-Lorem, a nonprofit foundation, announced today that its Founder, Chairman and CEO, Stanley T. Crooke, M.D., Ph.D., and Andrew W. Lo, Ph.D., Professor at the MIT Sloan School of Management and a member of n-Lorem’s board of directors, have published a commentary in Nature Biotechnology that proposes more economically feasible approaches to commercializing medicines for patients with extremely rare genetic diseases. The commentary was published contemporaneously with the issuance of the U.S. Food and Drug Administration (FDA) draft framework for accelerating the development of individualized treatments designed for patients with ultra-rare genetic conditions, and is consistent with previously issued guidance published by the FDA that supports rapid development of ASOs to treat nano-rare patients. As the draft guidance is available for public comment, the authors hope that the novel concepts proposed in the commentary will contribute to the publication of final guidance that provides a fulsome solution to the economic challenges facing drug developers hoping to address the needs of this desperate patient population.
Traditionally, nano-rare (affecting 30 people or fewer worldwide) and ultra-rare (affecting 7,000 people or fewer in the U.S.) diseases have not been considered viable candidates for commercial companies to pursue because the return on investment is unattractive, particularly when compared to more prevalent diseases, given current commercial regulatory requirements.
“I am delighted that the plight of patients and families dealing with extremely rare genetic diseases is now center stage and that the FDA is moving rapidly toward a thoughtful effective solution that can match the scale of the challenge. Though each nano-rare disease may affect only a small number of humans, in aggregate it is likely that hundreds of millions of humans are affected worldwide. The economic toll of these diseases is enormous as, in most cases, at least one wage earner in the family must stop working, but the emotional toll and lost productivity combined with the loss of hopes and dreams make the cost incalculable,” said Dr. Crooke.
“In the case of nano-rare diseases, economics is the main obstacle, not scientific means or regulatory hurdles,” said Dr. Lo. “With more creative financing structures and business models, we should be able to treat all nano-rare patients for whom we have viable therapeutic agents, hence we have an ethical obligation to pursue these financial solutions.”
“The challenge is to establish a path that assures that no patient is exposed to unnecessary or avoidable risks, but is sufficiently streamlined and cost effective to induce investment by commercial companies with responsibilities to shareholders. When the FDA issued the guidance for development of ASOs for nano-rare patients, it took a remarkably important step and our data at n-Lorem demonstrate that the ASO guidance already established strikes an ideal balance between protecting patients from unnecessary side effects and facilitating the rapid development of bespoke individualized ASO treatment. We hope that our data will contribute to the creation of truly effective commercial guidance as they clearly show that it is possible to find that ideal balance between safety and rapidly treating patients in need,” concluded Dr. Crooke. “At n-Lorem, we have shown that we can meet the needs of the rarest of patients. With effective commercial guidance based on the experience with current FDA guidance for ASOs, I am optimistic that we can scale to treat the greater population and leave no patient, no family behind.”
In their publication, Crooke and Lo outline several areas where improvements could help spur commercialization of ultra-rare and nano-rare therapies, including:
- Efficient Drug Discovery Technology: The need for rapid, automated, and cost-effective drug discovery platforms, such as n-Lorem’s ASO technology, that can convert genetic information into targeted therapies.
- Streamlined Regulatory Pathways: Extending the FDA’s current guidance for ASOs targeting nano-rare diseases, which allows for reduced non-clinical toxicology studies and bypasses animal models, to commercial development.
- Optimized Clinical Study Designs: Streamlining clinical trials for small patient populations, such as combining multiple ASOs in composite phase three studies or using intra-patient evaluations to assess treatment benefits.
- Innovative Pricing and Financing Models: Linking pricing to the number of treated patients, with transparency in costs and risk-adjusted returns, or amortizing costs over time for therapies with durable or lifelong benefits to reduce short-term financial burden.
On Feb. 23, 2026, the FDA released draft guidance that aims to accelerate approval of targeted individualized therapies when randomized, controlled trials are not possible because the number of patients suffering from an illness is limited. The guidance, which is currently open for comment, points to ASOs as an example where its new framework might be appropriate.
To learn more about this and listen to Dr. Crooke and Dr. Lo discuss their thoughts on the new draft guidance, listen/view the Podcast just released at www.nlorem.org/emerging-fda-draft-guidance-podcast.
About n-Lorem
n-Lorem Foundation is a non-profit organization established to apply the efficiency, versatility and specificity of antisense technology to charitably provide experimental antisense oligonucleotide (ASO) medicines to treat nano-rare patients diagnosed with diseases that are the result of a single genetic defect unique to only one or very few individuals. Nano-rare patients describe a very small group of patients (1-30 worldwide) who, because of their small numbers, have few if any treatment options. n-Lorem Foundation was created to provide hope to these nano-rare patients by developing individualized ASO medicines, which are short strands of modified DNA that can specifically target the transcripts of a defective gene to correct the abnormality. The advantage of experimental ASO medicines is that they can be developed rapidly, inexpensively and are highly specific. To date, n-Lorem received over 400 applications for treatment, more than 200 nano-rare patients approved, more than 40 INDs files with the US FDA and more than 45 patients currently on treatment. n-Lorem was founded by Stanley T. Crooke, M.D., Ph.D., former chairman and CEO of Ionis Pharmaceuticals, who founded Ionis Pharmaceuticals in 1989 and, through his vision and leadership, established the company as the leader in RNA-targeted therapeutics. Follow us on X, Facebook, LinkedIn and YouTube.
To learn more about n-Lorem’s mission at www.nlorem.org, and please consider giving to n-Lorem to bring hope, possibility and treatment options to these patients and families in need.
Contacts
n-Lorem Contact:
Amy Williford, Ph.D.
[email protected]
