Supporting Gene Therapy Research and Access for Minority Populations

Cell and gene therapies have a long history of addressing diseases with so-called “orphan” status. In fact, cutting-edge gene therapy strategies often target rare inherited diseases that affect smaller populations. The field as a whole has thus proven adept at developing treatments and securing funding for orphan diseases. Prominent examples include the first approved gene therapies for inherited retinal degeneration due to RPE65 mutation (LUXTURNA, voretigene neparvovec-rzyl) and SMA (ZOLGENSMA, onasemnogene abeparvovec-xioi). Despite these advances, there remains a critical need to increase research, resources, and access to gene therapies for diseases that predominantly affect minority or “orphan” communities.

Sickle cell disease (SCD), which affects more than 300,000 newborns each year worldwide, is most common in people of African, Hispanic, Middle Eastern, and South Asian descent. Indeed, 75-85% of affected children are born in Africa, where the mortality rate remains a heart wrenching 50-80% for those under five years of age. While the disease can be cured with bone marrow transplant, the majority (~85%) of SCD patients lack a suitably matched donor. The last five years have seen monumental progress in gene-based therapies for SCD, with the most exciting achievement being the advent of gene-addition strategies (i.e., insertion of a gene to prevent sickling of red blood cells). To date, over 50 patients have been treated as part of Bluebird Bio clinical trials testing a gene-addition therapy called LentiGlobin. For patients eligible for bone marrow transplant but without a suitable hematopoietic stem cell match, this approach adds an anti-sickling globin gene, Beta-globin, into a patient’s own hematopoietic stem cells and infuses them back into the patient. In the most recent phase I/II treatment cohort, the majority of patients showed minimal to no evidence of acute sickle cell symptoms in the months following treatment.

Despite the promise of this novel therapy and enthusiasm surrounding its clinical translation, challenges remain. First, this trial is only open at certain centers, and enrollment spots are limited. This lack of availability is due in part to under-investment in this and other treatments for minority populations. Furthermore, clinical trials for gene therapies for orphan diseases risk being aborted in favor of therapies that serve larger populations or are less complex. This lack of resources not only threatens our ability to advance these critical therapies to later phase trials and, ultimately, approval; it also hinders further work aimed at enhancing the safety profile while preserving efficacy. In addition, widespread support is needed to ensure these therapies are implemented earlier in life so that patients are treated prior to developing lifelong complications.

ASGCT has played a pivotal role in shining a spotlight on orphan diseases that can be treated and potentially cured with gene therapies. In addition to creating educational resources for patients and practitioners alike, ASGCT has promoted advocacy for research funding, highlighted these efforts in plenary and other symposia at annual meetings, and forged relationships with the FDA to underscore the importance of addressing barriers to the translation of these therapies.

During Black History Month, we wanted to pose the important question: What can we do to support the development of and increase access to cell and gene therapies for diseases that predominantly affect underrepresented minority communities? Moving forward, we have the following suggestions for the Society as a whole and its individual members:

1. Engage the patient community — a two-way conversation will allow education of patients and families regarding ongoing research, as well as perspective on future research priorities.
2. Work with industry partners to establish and maintain interest in investing in therapies for sickle cell and other diseases that disproportionately affect minority populations given the high potential to positively impact the disease.
3. Support scientists and physicians with funding opportunities to pursue development of novel and potentially more efficacious gene therapies for orphan diseases and diseases affecting minority populations.

Read the other posts in this series, Diversity and Inclusion Committee Plans to Expand Society’s Reach and Resources and Closing the Mentorship Gap for Minorities.

Dr. Abraham is an assistant professor at Children's National Hospital and Dr. Rouce is an assistant professor at Baylor College of Medicine. Both are members of the ASGCT Diversity and Inclusion Committee.