Lampalizumab

Disease Target Area:

Ophthalmology – People with geographic atrophy (GA) due to age-related macular degeneration (AMD)

About the Disease:

GA affects more than 5 million people worldwide, and visual impairment associated with GA tends to affect both eyes in many individuals. People with GA report visual problems with activities of daily living, including reading, driving, recognizing faces and activities in dim or low light. Geographic atrophy is a progressive and irreversible disease, as of 2019 there are no available treatments.

About the Program & What We Learned:

– Using a biomarker defined subgroup based on small Ph 2 is a high-risk approach – ensure visualization of individual patient data in future programs for full transparency of program risks
– Running an observational study in parallel can greatly enhance Ph 3 studies – enabled evaluation of prognostic component of biomarker hypothesis and exploration of link between genetics, imaging features, and clinical progression prior to defining statistical analysis plan for Ph 3
– Lack of replication of the prognostic effect of the proposed Ph 3 biomarker enabled us to prospectively lay out of a “back-up” plan for identifying other prognostic markers in the context of two sequentially unblinded Ph 3 studies
– Managed risk by gating investment in add-on diagnostics development until after Ph 3 read-out.

Reverse Translation:

– Rapid analysis of the Phase 3 data to identify robust predictors of GA progression (certain baseline imaging features) was incorporated into the design of current Phase 2 programs in GA (e.g. anti-Htra1).
– Phase 3 data was also used to evaluate the value of a historical retinal image and helped the current Phase 2 programs in GA incorporate historical or run-in imaging in order to better adjust for expected growth rates in the current Phase 2 study.
– Six highly-sensitive ELISAs to measure complement pathway activity were applied to aqueous humor samples from the Ph 3 study. This data confirmed that Lampalizumab inhibited Factor D, but indicate that more complete inhibition of the complement pathway may be achievable through other therapeutic approaches.