In August 2022, the U.S. Congress passed the Inflation Reduction Act (IRA) to reduce the cost of prescription drugs borne by patients. While many individuals certainly benefited from the legislation, the 30 million Americans suffering from rare diseases seem to have been left on the wayside.³

Due to the act’s provision that allows certain FDA-approved drugs, including those targeting multiple diseases and small molecule medicines, to be eligible for price negotiation after just seven years, one can anticipate a sustained slowdown in drug development and innovation. This stagnation is expected to be especially acute in rare disease research, as the field relies extensively on experimentation with repurposed drugs and small-molecule medicine to achieve medical advancements.

Alnylam Pharmaceuticals Inc., for example, halted its research on Stargadt treatment in October 2022, explicitly attributing the pause to the IRA.⁴ As Alnylam was basing its treatment on a drug that was approved to treat a different condition, the resulting cure would have been subject to price renegotiation.    

Since its enactment, the IRA has sent shockwaves across the world. Given that the U.S. plays a prominent role in biopharmaceutical research, the abrupt restrictions imposed by the IRA present a major setback to the global battle against rare diseases.

New hurdles on the horizon for India and the Indian Diaspora

One country that is likely to bear the brunt of the deceleration in rare disease research is India, a long-standing partner of the U.S. in this field. With 70 to 96 millions living with rare diseases,⁵ many of which are unique to the Indian subcontinent, India has its hands full managing these conditions.

The Indian government has a great start in 2021 with the Ministry of Health and Family Welfare formulating and adopting a National Policy for Rare Diseases (NPRD) that includes a one-time treatment subsidy of USD 61,000 per patient. The program initially promises to be accessible to 40% of the population and has since established over 11 diagnostic and treatment centers of excellence across the country.⁶

However, this program needs significant expansion to cover all 10,867 (and growing) known rare diseases and not just those small number of currently treatable rare diseases. The policy currently only covers persons afflicted by a subset of the 450 recognized rare diseases. The implementation of NPRD will also need to at least triple the number of centers of excellence to meet the needs of the entire rare disease population of India and provide more accessibility across the country including the rural population. As for the diagnostic and treatment centers, their impact is currently hampered by the absence of formal referral channels established between primary care, secondary care, and tertiary care centers, which hinders patient access.

“A national policy with funding is a great start but is insufficient to cover the treatment of many rare diseases as orphan drugs have to be imported into India,” says Dr. Harsha Rajasimha, founder and executive chairperson of IndoUSrare, a nonprofit centered on combating rare diseases through cross-border collaborations. “Furthermore, many known rare conditions in the U.S. such as ALS (also known as Lou Gehrig’s disease or motor neuron disease (MND)), ultra rare indications caused by single gene mutations such as ADSSL1, DLG4, MNGIE, VCP, and SYNGAP, are not officially recognized by NPRD, thus leaving over 90% of the rare diseases on the fence. Thousands of rare diseases fall under the realm of genomics, precision medicine, patient registries, and clinical research. This is where IndoUSrare seeks to collaborate with the GoI, patient groups, and industry stakeholders to foster cross-border collaborations to accelerate research and clinical trials.” Says Dr. Rajasimha who has also pioneered an intelligent technology platform for efficient implementation of patient registries and clinical trials.

The call for more inclusive research and clinical trials

Considering the rare disease research slowdown in the U.S. and the growing concerns about these disorders in India, increased Indo-US collaboration, particularly in the context of clinical trials, can help mitigate consequences.

The U.S. conducts nearly half of the global clinical trials for rare diseases. However, these trials are not representative of the country’s ethnic makeup, underrepresenting many diasporas, Indian included. For example, despite India having one-third of all rare disease cases worldwide, only nine of the 202 trials registered in the U.S. were conducted there. Participation of the Indian diaspora in these trials is hardly better; in the 193 trials that did not take place in India, only 1% of participants were of Indian origin.⁷

This lack of representation in clinical trials is problematic because it raises questions about the applicability of the findings; different patient groups may respond differently to identical treatments. This is relevant for specific Indian demographics, as their long history of genetic isolation and unique cultural practices may shape the way they respond to treatments.

By failing to capture the ethnic diversity within the U.S., these non-representative clinical trials may not only lead to a misinterpretation of treatment effects on American rare disease patients but also impede India’s efforts due to the absence of Indian participants. Indeed, considering the additional costs associated with conducting clinical trials in India, Indian regulators have in the past waived the requirement for representative trials if the orphan treatment has already been approved by the U.S. Food and Drug Administration. Consequently, Indian patients may at times receive treatments may be ineffective for them.

“Without a diverse base of study participants, researchers lack representative data on disease progression and research efficacy,” says Frank Sasinowski, MS, MPH, JD, Director at Hyman Phelps McNamara P.C., and Founding Board Member of IndoUSrare.

The need for more inclusive clinical trials is timely because it provides both the U.S. and India with an opportunity to deepen their understanding of the rare diseases affecting both countries — even under the clamping effect of the IRA. Cross-border initiatives, such as those focused on research digitization, data sharing, and the creation of patient registries, can increase the participation of Indian patients as well as those from other groups in these trials.

Coming to a head in the Bridging RARE Summit 2023

Though the U.S. deserves to be congratulated on the 40th anniversary of the Orphan Drug Act of 1983, recent policy changes such as the IRA have stifled biopharmaceutical innovation in the field of rare diseases. This shift is poised to exacerbate India’s struggles in addressing these disorders as it endeavors to improve access to orphan drugs and advance rare disease research and treatment.

One way for both countries to alleviate the fallout resulting from the IRA is to invoke their trusted biopharmaceutical partnership. Collaborative research efforts can expedite the development of treatments, expand their accessibility to regions in pressing need, and pave the way for more inclusive clinical trials.

The intricacies of managing rare diseases, including challenges and potential solutions, will be explored in greater depth during the two-day Bridging RARE Summit 2023. Join the host, IndoUSrare, alongside representatives from the rare disease community, on October 29-30 in this culminating event.

The Summit planning committee has selected two legendary leaders to honor this year with the Abbey Meyers Khushi Bridging RARE Award in recognition of their dedicated lifetime of achievements to foster cross-border collaborations in the field of rare genetic and undiagnosed diseases. The two honorees this year are Dr. William A. Gahl, Senior Investigator at the National Human Genome Research Institute, National Institutes of Health, and Padmashri Dr. Ishwar Chander Verma, Senior Advisor at the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, Delhi. “The U.S. and India possess complementary skillsets and resources in the context of researching and treating rare diseases,” says Dr. Verma upon accepting the award. “Collaboration is the way forward.”

“Dr. Abbey Meyers is a living legend who was instrumental in the enactment of the U.S. FDA Orphan Drug Act of 1983 which has had immense impact in the U.S. and kicked off a global crusade. By honoring these legends who have advanced research in rare and undiagnosed diseases, the Indo US Organization for Rare Diseases together with the Bridging RARE planning committee seeks their vast wisdom and guidance to carry forward the mission of catalyzing cross-border collaborations for patient-focused research and the next generation of affordable orphan drug development.” Says Rajasimha.

IndoUSrare thanks the Gold Sponsors of the Indo US Bridging RARE Summit 2023, Exela Pharma Sciences and Soleno Therapeutics.

About the Bridging RARE Summit:
The Bridging RARE Summit 2023 is organized by the Indo US Organization for Rare Diseases, a non-profit organization based in the Biohealth capital region and a platinum member of the National Organization for Rare Diseases (NORD). The main collaborating U.S. and Indian organizations for the 2023 Summit include George Mason University, Virginia BIO, BioHealth Capital Region Forum, All India Institute of Medical Sciences (AIIMS) New Delhi, Centre for DNA Fingerprinting and Diagnostics (CDFD) India, Global Genes, EveryLife Foundation for Rare Diseases, other collaborators and sponsors. For the full agenda, keynote speakers, Gala, Registration, and Sponsorship opportunities, visit https://bridgingrare.org.

About Indo US organization for rare diseases:
IndoUSrare is a humanitarian nonprofit 501(c)(3) tax-exempt public charity organization based in the United States. Founder and Executive Chairman Dr. Harsha Rajasimha, who lost a child to a rare disease in 2012, has been a rare disease advocate for more than 10 years. To address the unmet needs of diverse patients with rare diseases globally, the leadership team comprised of experienced professionals from research, advocacy, regulatory, and drug development seeks to build cross-border collaborations connecting stakeholders of rare diseases in low- and middle-income regions such as India, with their counterparts and clinical researchers in the United States to improve the diversity of clinical trial participants, accelerate research and development, and improve equitable access to life-saving therapies to diverse populations of rare disease patients. Visit https://indousrare.org.

References:

1. Ministry of Health and Family Welfare. “National Policy for Rare Diseases, 2021.” Ministry of Health and Family Welfare, rarediseases.mohfw.gov.in/uploads/Content/1624967837_Final-NPRD-2021.pdf. Accessed 16 Sep. 2023.
2. Roberts, Alexis-Danielle, Roopma Wadhwa. “Orphan Drug Approval Laws.” National Library of Medicine, ncbi.nlm.nih.gov/books/NBK572052/. Accessed 16 Sep. 2023.
3. Saltonstall, R.K., Peter L. (2023). The IRA needs changes to better support patients with rare diseases. [online] STAT. Available at: Accessed 9 Oct. 2023.
4. Scott, R. (2022). Alnylam Opts Against Phase III Trial for Vutrisiran in Stargardt Disease – Updated. [online] BioSpace. Available at: Accessed 9 Oct. 2023.
5. Salian, Priti. “What price a child’s life? India’s quest to make rare disease drugs affordable.” The Guardian, theguardian.com/global-development/2021/mar/15/what-price-a-childs-life-indias-quest-to-make-rare-disease-drugs-affordable. Accessed 16 Sep. 2023.
6. Ministry of Health and Family Welfare. “National Policy for Rare Diseases, 2021.” Ministry of Health and Family Welfare, rarediseases.mohfw.gov.in/uploads/Content/1624967837_Final-NPRD-2021.pdf. Accessed 16 Sep. 2023.
7. Chakraborty, Monoswi et al. “Rare disease patients in India are rarely involved in international orphan drug trials.” PLOS Global Public Health, journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0000890. Accessed 16 Sep. 2023.

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