The Food and Drug Administration has approved 16 new gene therapies to date, but for most people around the world, these expensive treatments remain financially out of reach. Dr. Harsha Rajasimha, Founder and CEO of Jeeva Clinical Trials Inc., explains that making gene therapies, particularly for rare diseases, available to the world requires the creation of global patient registries or digitizing the rare diseases’ natural histories including in emerging markets to ensure that data sets are inclusive of global populations.
MANASSAS, Va., Dec. 12, 2023 /PRNewswire-PRWeb/ — Impressive advances have been made during 2023 by the U.S. Food and Drug Administration (FDA) in terms of approval of gene therapies and a push to spur the development of therapies for rare diseases. With the latest FDA approval of gene therapy for Sickle Cell Disease, sixteen new gene therapies have been approved to date, and 40 novel drugs in 2023 alone, up from 37 in 2022.(1) Unfortunately, analysis by the Institute for Clinical and Economic Review (ICER) found the average cost of gene therapy remains beyond the reach of most, costing between $1 million and $2 million per dose.(2) Global Patient Registries offer a way to dramatically increase patient access and inclusion in rare disease research and clinical trials. This could ultimately reduce the cost of these therapies while improving access and efficacy across a more diverse group of people, says Dr. Harsha Rajasimha, Founder and CEO of Jeeva Clinical Trials Inc.
Better Access, More Solutions
Without globally inclusive patient registries, advancements in research and development of cures for rare diseases become less equitable and accessible. “What we need are registries focused on a given disease globally, not biased by a regional population, so as to benefit all patients,” he says. Creation of well-designed patient registries that include highly populous countries like India provide the data needed to compile a complete understanding of the natural history of a disease, accelerating the global advancement of the development of treatment efforts. The current system is inefficient and misses the reality of the differences in how patients in low-and-middle-income-countries (LMICs) such as India might experience a disease versus how patients in the western world do, due to variability in genetics, infrastructure, environmental, and lifestyle factors. Patient registries have also proven to be valuable databases for accelerating patient recruitment for clinical trials.
Rajasimha explains how Jeeva provides a user-friendly and affordable platform to create high-quality patient registries that empower researchers to better understand the disease heterogeneity and natural history in the general population and the need to expand beyond the Caucasian population.
In October 2023, Dr. Rajasimha chaired the Indo U.S. Bridging RARE Summit 2023, which shone a spotlight on the recent gene therapies approved by the FDA. Dr. Peter Marks’s keynote address at the conference highlighted the need for global collaboration and cooperation on the creation of patient registries, clinical trials, and orphan drug launches, including in countries like India, to combat the currently biased datasets and to ensure the benefits of gene therapy advances are accessible and affordable. For instance, a global registry of all people affected by sickle cell disease could be more effective than having regionally siloed registries.
The recent launch of the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program could be a game changer. The idea is to treat each rare disease as a global public health emergency and make “operation warp speed” a reality on an ongoing basis at affordable costs. It is open to sponsors of products currently in clinical trials under an active Investigational New Drug application (IND). START’s goal is to provide advice and regular ad-hoc communication with FDA staff to address product-specific development issues, including, but not limited to, clinical study design, control group choice, and fine-tuning the patient population.
Successful Outcomes with Gene Therapies
More and more, gene therapies are offering improved outcomes for diseases. A new study by the Tufts Medical Center’s New Drug Development Paradigms (NEWDIGS) program, funded by the Alliance for Regenerative Medicine, found that durable cell and gene therapies for blood cancers and orphan diseases are 2 to 3.5 times as likely to succeed than other therapeutic modalities for similar conditions.(3)
Profound genetic hearing loss due to mutations of the otoferlin gene has had positive results using gene therapy in two separate trials. While this mutation is rare, causing only 1 to 3% of cases of hearing loss, the successful trial represents a crucial step forward, as there are currently no treatments for hearing loss except cochlear implants.(4)
As of November 21, 2023, more than 5,900 clinical trials are underway focused on some form of gene therapy.(5) The number of people worldwide living with a rare disease is estimated to be 300 million, affecting at any point in time somewhere between 3.5 to 5.9% of the population.(6)
Make Treatments Global
These advances are exciting, but global treatment availability is necessary for all patients to benefit. The enactment of The Orphan Drug Act (ODA) of the US FDA in 1983 has aided the approvals of about 1100 orphan drugs, as it provided financial incentives for companies to focus on combating these rare conditions.
However, as we celebrate the 40th anniversary of ODA, Rajasimha explains, all stakeholders recognize that the patients in these trials have not been representative of the global population, as most of the trial participants have been limited to the U.S. and the European Union. A biased data set leads to biased treatment development, leaving out almost 90% of the world’s population from receiving the same treatment benefit.
Additionally, advances in artificial intelligence and machine learning present an opportunity to expand patient registry data. Still, AI and machine learning models are likely being trained based on the available biased datasets, meaning that insights gained from these advances in AI and ML are limited and unlikely to benefit most global citizens.
Registries Form the Foundation for Addressing Health Economic and Other Inequities
Regarding treatments for rare diseases, economics is still hindering greater advancements in science and medicine. Questions remain about the ability of patients to afford treatments and whether governments will be able to negotiate with the regulatory review and approval process to increase access.
Rajasimha stresses how relying on regional patient registries does not permit economies of scale that allow biotech companies to progress on their gene therapies pipelines. “Small and emerging biotech companies that are investing in research and development of gene therapies for rare diseases may find it impossible to recover the cost of R&D by recruiting from regional registries alone that may only have a few hundred patients,” he explains. But with global registries, that number could grow to thousands for a particular disease, creating a much greater opportunity to understand the disease epidemiology and heterogeneity, including most patients, and to allow biotech companies to recoup their expenses post approval by the regulators.
Engaging the rest of the world (regions beyond the U.S. and E.U.) in patient registries and orphan drug development is essential to overcome the challenges of DEIA in rare diseases research. These are critical success factors that impact the downstream recruitment of patients for clinical trials and the eventual commercialization of successful drugs.
Jeeva’s eClinical Cloud is a versatile unified platform for creating global patient registries. It has recently launched an emerging markets program to help address these massive inequities and access challenges to help engage low-and-middle-income countries (LMICs) to participate in the rare disease revolution. The platform allows researchers to engage researchers and patients remotely, collect data in real-time and achieve patient retention during long-term follow-ups, a crucial issue for many clinical trials.
Jeeva’s modular platform includes electronic data capture (EDC) module compliant with the FDA 21 CFR part 11 and other regulatory guidelines yet affordable for nonprofit patient organizations and public health institutions. EDC is a software used for collecting clinical trial data via electronic (usually web-based) case report forms (eCRFs) and questionnaires for gathering information about a study participant. The primary goal of this platform is to ensure that researching rare disease solutions becomes more productive for biotech companies in emerging markets. It is vital for regulatory bodies such as the FDA accept this clinical trial data from these other countries, an issue that the START program is working to address.
Rajasimha was a speaker on these topics at the Society for Clinical Data Management India conference on December 1st in Bengaluru and the Indian Academy of Medical Genetics (IAMG) conference on December 2nd in New Delhi.
Rajasimha concludes, “We need to go global because we don’t have quality clinical data in the rest of the world like we do in the U.S. and Europe. During my two decades of research experience, it has perplexed me that biomedical science is data-driven, yet very little attention goes towards ensuring that the data is inclusive and representative of all humans. It’s incomplete and biased science. We really need to help the creation of national, international, and global patient registries including in countries such as India and the rest of the world, for all rare and neglected diseases. It is a prerequisite to accelerating the research and development of treatments of rare diseases that can be affordable, accessible and beneficial to all people.”
About Jeeva Clinical Trials Inc.
The personal experience of losing a child born with a rare congenital disorder and a brother with a chronic disease became the springboard for Dr. Harsha Rajasimha to apply his years of postdoctoral research experience at the NIH and FDA to accelerate therapies for rare and common conditions. He founded Jeeva with the mission of lowering the cost of drug development and accelerating the speed of clinical trials by purpose-building a modern technology platform that empowers sponsors to run clinical trials, with fewer fragmented systems, fewer employees, with significantly less burden on clinical researchers and patients, which has allowed for a more globally diverse population to access clinical trials remotely.
Today the Jeeva eClinical Trial platform supports sponsors and CROs across the globe helping reduce the logistical burdens on patients and study teams by over 70%. Its complete suite of technology supports fully decentralized and hybrid clinical trials and has resulted in being selected by research hospitals, CROs, and sponsors developing pioneering therapeutics such as Frantz Viral Therapeutics and ImmunoACT. The Virginia-based company’s modular cloud-resident software-as-a-service is highly scalable and facilitates patient enrollment, engagement, and evidence generation in clinical trials from one login from any browser-enabled mobile device. Visit https://jeevatrials.com/
1) Eglovitch, Joanne S.; “Convergence: CBER chief discusses priorities, touts gene therapy approvals”; Regulatory Focus; 5 October 2023; raps.org/News-and-Articles/News-Articles/2023/10/Convergence-CBER-chief-discusses-priorities,-touts.
2) “Cell and Gene Therapy Manufacturing Costs Limiting Access”; Genetic Engineering & Biotech News; 21 February 2023; genengnews.com/insights/cell-and-gene-therapy-manufacturing-costs-limiting-access/.
3) Pratap, Aayushi; “Study Highlights Standout Clinical Success of Certain Cell and Gene Therapies”; BioSpace; 6 November 2023; biospace.com/article/study-highlights-superior-clinical-success-of-certain-cell-and-gene-therapies-/.
4) “Gene Therapy Racks up Success in Rare Genetic Hearing Disorder”; Inside Precision Medicine; 30 October 2023; insideprecisionmedicine.com/topics/patient-care/gene-therapy-racks-up-success-in-rare-genetic-hearing-disorder/.
5) Clinical Trials; Accessed 21 November 2023; classic.clinicaltrials.gov/ct2/results?recrs=&cond=&term=gene+therapy&cntry=&state=&city=&dist=.
6) “New scientific paper confirms 300 million people living with a rare disease worldwide”; Rare Disease International; 15 October 2019; rarediseasesinternational.org/new-scientific-paper-confirms-300-million-people-living-with-a-rare-disease-worldwide/.