- During a second quarter earnings presentation Wednesday, gene therapy developer Regenxbio unveiled a mixed bag of interim data for two of its leading programs that appears to have caused more concern than optimism among investors.
- On the brighter side, early results from a Phase 1/2 trial of Regenxbio's treatment for wet age-related macular degeneration (AMD) indicate there have been no drug-related adverse events or drug-related serious AEs. Known as RGX-314, the treatment delivers a gene to the eye and showed a dose-dependent increase in expression of a protein that targets vascular endothelial growth factor (VEGF). Regenxbio plans to move RGX-314 into Phase 2 "as soon as possible."
- Less positive were data surrounding the company's investigational therapy for homozygous familial hypercholesterolemia, RGX-501. A Phase 1/2 trial testing two dose cohorts of the therapy so far hasn't found a clinically meaningful change in "bad" cholesterol levels in the lower-dose cohort. Additionally, trial runners have reported two drug-related SAEs and four total SAEs over the 52-week active study period.
Scientific breakthroughs over the last few decades have helped gene therapies evolve into a viable market opportunity — exemplified most prominently last year, when the Food and Drug Administration gave a first-of-its-kind approval to Spark Therapeutics' treatment for a rare eye disease, Luxturna (voretigene neparvovec).
Drugmakers are still far from ironing out all the intricacies of gene therapy development, however. Case in point: Spark lost nearly $1 billion of its value earlier this week as questions loomed over the safety and competitive edge of its investigational hemophilia treatment.
Safety could have played a role as well in Regenxbio's stock falling more than 12% at market's open Wednesday.
Regenxbio reported in January that a patient in the first cohort of its Phase 1/2 RGX-501 trial experienced an SAE within 24 hours of dosing. The patient had abnormally low blood pressure linked to a mild inflammatory response. Though the patient's condition was resolved in a matter of hours, Regenxbio noted the "nature and time frame of the SAE is distinct from expected and known immune responses to [adeno-associated virus] therapy."
And the latest data suggests safety remains an issue with RGX-501. A patient in the trial's second cohort experienced transient elevation in amino acid-forming enzymes called transaminases, according to Regenxbio, and was briefly hospitalized as a result. In fact, all three subjects in the second cohort had elevated transaminase levels about a month to a month and a half after dosing. The subjects were asymptomatic, though, and treated with corticosteroids to bring back down their enzyme levels.
On efficacy, patients in Cohort 1 showed no significant reduction in low-density lipoprotein cholesterol (LDL-C), while Regenxbio hypothesized the immune responses seen in Cohort 2 and the resulting steroid therapy may be muddying investigators' ability to evaluate LDL-C levels at 12 weeks.
A data safety monitoring board has reviewed the interim data on RGX-501, and Regenxbio plans to amend the Phase 1/2 trial to include preventative steroid therapy and to evaluate LDL-C levels farther along in treatment. The company also intends to increase enrollment in Cohort 2 and tack on a third cohort that will receive steroid prophylaxis.
As for RGX-314, interim data showed a dose-dependent benefit for certain measures of eye health, such as the number of letters a patient can read on an eye chart or the number of anti-VEGF injections needed.
BCVA (as measured by Early Treatment Diabetic Retinopathy Study letters) from baseline to six months
|Cohort 1||Cohort 2||Cohort 3|
|Number of patients||5||6||6|
|Mean change from baseline||-2||+7||+8|
|Median change from baseline||-3||+9||+4|
Regenxbio is adding a fourth cohort to the Phase 1/2 study, which will receive 1.6 x 10^11 genome copies (GC) per eye, higher than the three other cohorts of 3 x 10^9 GC per eye, 1 x 10^10 GC per eye and 6 x 10^10 GC per eye. The Phase 2 portion of the study should kick off in 2019.
"We are encouraged by the positive signals we are seeing in Cohort 3 in these hard-to-treat wet AMD subjects with long-standing disease. We are excited to have initiated dosing at a higher dose in Cohort 4 to further evaluate the dose response and look forward to starting a Phase 2 trial next year," Stephen Yoo, Regenxbio's chief medical officer, said in an Aug. 8 statement.