FDA issues guidance on drug development for neovascular age-related AMD
The US Food and Drug Administration (FDA) has issued draft guidance for industry on the development of drugs to treat neovascular or “wet” age-related macular degeneration, an eye disorder that can lead to blindness.The draft guidance, issued on 24 February 2023, offers the agency’s recommendations for clinical trials of drugs and biologics, including eligibility criteria, trial design and efficacy endpoints. The document was developed jointly by the FDA’s Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER).
Trial design
For trial design, the agency recommends parallel-group, randomized by patient, double-masked trials in which the investigational drug shows superiority over the control group. Sponsors could also use a parallel-group, randomized, double-masked trial to show noninferiority of an investigational drug to either ranibizumab injection or aflibercept.
Sponsors conducting comparative clinical trials should have at least one comparator arm for each investigational drug arm, with the same dosing frequency, criteria for dosing adjustments and criteria for interventions, the agency advised.
The trial population should include patients older than 50 years of age, with both men and women, multiple racial and ethnic groups and people of various eye colors. To be included, patients should also have documented choroidal neovascularization.
When conducting a superiority trial, the draft guidance calls for enrolling patients with neovascularization cause by age-related macular degeneration “who have had visual loss or would be expected to develop visual loss.” Noninferiority trials, on the other hand, should enroll patients with neovascularization caused by age-related macular degeneration “who have visual loss.”
Efficacy
When seeking to demonstrate the efficacy of drugs or biologics to treat neovascular age-related macular degeneration, FDA recommends that sponsors show one of the following:
- A statistically significant smaller percentage of patients with a doubling of the visual angle in best corrected distance visual acuity at nine months or later, compared with the control group.
- A statistically significant larger percentage of patients with a halving of the visual angle in best corrected distance visual acuity at nine months or later, compared with the control group.
- A statistically significant difference between groups in mean best corrected distance visual acuity of 15 or more letters at nine months or later.
- The lower bound of a two-sided, 95% confidence interval for the difference between the investigational drug group and the ranibizumab injection group is greater than or equal to -4.5 letters in mean best corrected distance visual acuity at nine months or later; or the lower bound of a two-sided, 95% confidence interval for the difference between the investigational drug group and the aflibercept group is greater than -4.5 letters in mean best corrected distance visual acuity at nine months or later.
Safety
To evaluate safety of drug and biologic treatments for neovascular age-related macular degeneration, FDA recommends enrolling 400 or more patients who are using the investigational treatment with a concentration and dosing frequency that is the same or more than what is proposed for marketing. At least 300 patients should have completed at least nine months of follow-up before sponsors submit a marketing application, according to the draft guidance.
The agency also advises that sponsors conduct at least one concurrently controlled safety trial of at least two years’ duration.
Comments on the draft guidance can be submitted to regulations.gov and labeled as Docket No. FDA-2022-D-0073. The public comment period closes on 30 May 2023.
Draft guidance on neovascular AMD drug development
