Annexon's eye disease med improved vision in a phase 2 trial but flunked the primary goal. The CEO was thrilled

Annexon chief executive Doug Love is about as optimistic as you can be after failing a clinical trial.

“We love it,” was his response in an interview with Fierce Biotech when asked for his thoughts on the results from an unsuccessful phase 2 for ANX007. The geographic atrophy (GA) med ANX007 did not improve the growth of lesions compared to placebo, which was the main goal of the study, according to a release late Wednesday. GA is a form of age-related macular degeneration marked by difficulty seeing in low light and reduced vision sharpness.

What’s to love when you fail? Treated patients reported improved vision as measured by their ability to read three lines of letters on a common vision test, especially those who received ANX007 once a month.

The trial found that patients given 5 mg of ANX007 had a 72% reduction in 15-letter loss, compared to placebo. Patients given the same dose of the drug every other month had a 48% reduction, although with a p-value of 0.064. Love says the reason for the discrepancy between improvement in vision versus lesion growth is the stage in the complement system being targeted.

Annexon is aiming ANX007 at C1Q, a higher stream target on photoreceptor synapses that the company hypothesized would improve the cascade effects limiting vision loss. But it failed to stop all downstream effects, namely lesion growth, which Love said is often targeted by clearing out debris in the cells behind the photoreceptors. Love brushed off the primary endpoint flop, arguing that vision improvement will differentiate the company on the market and will be the clinical development focus moving forward.

“We're trying to tackle these diseases, where we can provide functional benefit to patients across the body, the brain and the eye,” he said. “We've shown nice evidence of that—we're all in on this now with regard to GA function as the endpoint.” 

The phase 2 ARCHER trial enrolled 270 patients and randomized them to receive 5 mg of ANX007 once a month, 5 mg once every other month, or a placebo either once a month or once every other month. The average age of enrolled patients was 80. The dropout rates were 18% and 16.3% in patients receiving ANX007 monthly or every other month, respectively, and 14% for placebo, according to presentation slides. 

The available data suggest a clear therapeutic edge to treating patients once a month, though Love wouldn’t outright side with the regimen given the age of patients, saying that’s a “marketplace dynamic that will have to play out.” In other words, given the age of the patient population, demand for every-other-month dosing may be high even if it comes with reduced benefit. 

It’s unclear whether ANX007 is able to slow vision loss in low-light areas, though the company says the treatment “demonstrated a trend” in slowing progression. The p-values for both the monthly and every other month regimens exceed 0.05, however. 

Love and Annexon will now head to regulators' offices to plan for a phase 3 trial, with Love saying the study design is already prepared. The company is chasing Apellis Pharmaceuticals, which has an approved GA therapy on the market, and Iveric Bio, whose GA med has a mid-August FDA approval decision deadline. Love was coy about when he expects to launch the phase 3 study but said it’s “in and around” the end of the year. 

The biotech CEO optimistically compared Annexon’s trajectory to Regeneron and Eylea, saying that while others have and will get to the market first, they might ultimately not be as impactful.  

“We think we have the potential to be similarly situated,” said Love. “We'll start making really strong decisions in and around commercial strategy and spin after we get into the phase 3 study.”