Abstract
This study characterizes government, academia, and private funding for gene therapy trials in the United States by technology type and therapeutic and disease area.
Since 2017, the US Food and Drug Administration (FDA) has approved 4 gene therapies: tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta) for cancer, voretigene neparvovec-rzyl (Luxturna) for a genetic form of blindness, and onasemnogene abeparvovec-xioi (Zolgensma) for spinal muscular atrophy. Although clinically transformative, they carry list prices of $475 000, $373 000, $425 000, and $2.1 million, respectively, for 1-time infusions. High development costs and the need to incentivize innovation are common justifications for such prices. However, public funding played an important role in each product’s invention and clinical testing.1,2,3,4,5
As more gene therapies appear, debate about the relative roles of the National Institutes of Health (NIH), academia, and industry in drug development will continue. To provide data to this discussion, we quantified sources of sponsorship and funding for gene therapy trials in the United States.
Methods
We searched ClinicalTrials.gov on August 29, 2019, using the following terms based on the FDA definition of gene therapy and known gene therapy trials: gene therapy(ies), genetic therapy(ies), gene transfer(s), genetic transfer(s), viral vector(s), transduce(d), and genetic engineering. We collected information on each trial’s intervention, phase, treated condition, number of participants, sponsor, and funders. The sponsor is the single entity with authority over the study. The funder was defined as any entity listed as a sponsor or collaborator, which includes any entity providing funding or support—a definition consistent with a prior analysis.6
To focus on recent US trials, we excluded those with a completion date before January 2019; those with a terminated, withdrawn, or suspended status; and those conducted outside the United States. Two raters (Z.K. and B.K.) assessed whether remaining trials met the FDA gene therapy definition and categorized interventions based on whether the therapy was intended to correct a genetic defect and whether it involved inserting genetic material directly into patients (in vivo) or into extracted cells administered to patients (ex vivo). We calculated the number of trials by sponsor and funder (ie, the NIH, academia [hospitals and universities], and biopharmaceutical companies [“industry”]), stratified by treated condition, intervention, and trial phase.
Results
Our search terms yielded 826 trials, of which 341 met inclusion criteria. Among included trials, 130 (38%) were for in vivo therapies, 107 (31%) for therapies that correct genetic defects, and 221 (65%) for cancer therapies (Table). Thirty-five trials (10%) were sponsored by the NIH, 135 (40%) by industry, 85 (25%) by hospitals, and 86 (25%) by universities. The NIH contributed funding to 29% of the trials, industry to 46%, and academia (hospitals and universities) to 54% (Table). Additionally, 36% of trials were funded solely by industry, whereas 50% were funded solely by academia or the NIH.
Table. Sponsorship and Funding of Gene Therapy Trials in the United States as Listed in ClinicalTrials.gov.
| No. (%) | |||||||
|---|---|---|---|---|---|---|---|
| Overall | Technology Type | Therapeutic Area | Disease Area | ||||
| In Vivo | Ex Vivo | Correcting Genetic Defect | Other Usesa | Cancer | Noncancerb | ||
| Total No. | 341 | 130 | 211 | 107 | 234 | 221 | 120 |
| Sponsorshipc | |||||||
| NIH | 35 (10) | 12 (9) | 23 (11) | 11 (10) | 24 (10) | 26 (12) | 9 (8) |
| Industry | 135 (40) | 79 (61) | 56 (27) | 65 (61) | 70 (30) | 60 (27) | 75 (63) |
| Academiad | 171 (50) | 39 (30) | 132 (63) | 31 (29) | 140 (60) | 135 (61) | 36 (30) |
| Hospital | 85 (25) | 21 (16) | 64 (30) | 13 (12) | 72 (31) | 70 (32) | 15 (13) |
| University | 86 (25) | 18 (14) | 68 (32) | 18 (17) | 68 (29) | 65 (29) | 21 (18) |
| Fundinge | |||||||
| NIH | 100 (29) | 31 (24) | 69 (33) | 24 (22) | 75 (32) | 77 (35) | 23 (19) |
| Industry | 157 (46) | 84 (65) | 73 (35) | 71 (66) | 86 (37) | 74 (33) | 83 (69) |
| Academiad | 183 (54) | 45 (35) | 138 (65) | 35 (33) | 148 (63) | 142 (64) | 41 (34) |
| Hospital | 121 (35) | 25 (19) | 96 (45) | 15 (14) | 106 (45) | 105 (48) | 16 (13) |
| University | 100 (29) | 23 (18) | 77 (36) | 25 (23) | 75 (32) | 71 (32) | 29 (24) |
Abbreviation: NIH, National Institutes of Health.
Refers to therapies that do not strictly replace or correct a defective gene but use gene modification techniques to correct nongenetic problems (eg, chimeric antigen receptor therapies involve the genetic modification of T cells to enhance their ability to recognize and destroy cancer cells).
The most common noncancer diseases include hematologic disorders, ophthalmologic disorders, and immune deficiencies.
The sponsor is listed in ClinicalTrials.gov and defined as the entity with authority over the study. For sponsorship, total percentages may not add up to 100 because of rounding.
Academia includes both hospital and university sources of sponsorship and funding; a single trial has 1 sponsor but may be funded by both hospitals and universities.
Funders include any sponsors or collaborators, defined as entities that contributed any study funding or support listed in ClinicalTrials.gov. Individual trials may receive funding from multiple institutions (ie, the NIH, industry, academia), so the number of trials may add up to more than 341. There are 14 trials (4%) that also received some amount of funding from other US federal organizations or nonprofit organizations; these organizations never appear as sponsors.
Sponsorship varied by trial type and phase (Table). Industry sponsored 61% of in vivo trials, 61% of trials for therapies correcting genetic defects, 63% of noncancer trials, 27% of ex vivo trials, 30% of trials for therapies not correcting genetic defects, and 27% of cancer trials. Industry sponsored 22% of phase 1 trials, 55% of phase 2 trials, and 100% of phase 3 trials (Figure). Among sponsor type, median enrollment differed by trial phase (phase 1: NIH, 27; industry, 23; hospital, 19; university, 18; phase 2: NIH, 43; industry, 27; hospital, 25; university, 16; phase 3: industry, 55).
Figure. Number of Gene Therapy Trials in the United States by Sponsor Type and Phase as Listed in ClinicalTrials.gov.
NIH indicates National Institutes of Health.
Discussion
Among gene therapy trials listed in ClinicalTrials.gov and active as of January 2019, the biopharmaceutical industry sponsored or funded less than half (46%) and was the sole funder for 36%. However, this involvement varied by trial type and phase. Industry sponsored all phase 3 trials, but the NIH and academia sponsored almost half of phase 2 trials, which—as with tisagenlecleucel and axicabtagene ciloleucel—may serve as the final phase of testing for many gene therapies reviewed under expedited FDA pathways.
This analysis is limited to US trials identified by the search terms in ClinicalTrials.gov, cannot independently verify funding sources or amounts, and does not account for preclinical support. Nonetheless, it illustrates that the NIH and academia are deeply involved in more than just basic science discovery for gene therapy.
Section Editor: Jody W. Zylke, MD, Deputy Editor.
References
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