Apellis sets up another phase 3 program for lead drug APL-2

It's been a good summer for Apellis, which has just reported positive midstage data for its lead candidate in age-related macular degeneration (AMD) a couple of weeks after it raised $60 million in a series E round.

With the additional funds (PDF) and phase 2 data in hand, Apellis can now accelerate plans to start a phase 3 program for lead candidate APL-2 in the dry form of AMD, which could be a second and much larger late-stage indication for the complement C3 inhibitor after rare blood disorder paroxysmal nocturnal hemoglobinuria (PNH).

Top-line results from the newly reported FILLY trial show that APL-2 met its primary objective of holding back the progression of geographic atrophy (GA), an advanced form of AMD, compared to a sham therapy.  

Giving the drug by intravitreal injection once a month cut progression by 29% over 12 months, while dosing every other month reduced it by 20%. Moreover, zeroing in on the second half of that period revealed an even stronger effect, with GA progression cut 47% and 33% compared to sham.

Apellis' CEO Cedric Francois, M.D., Ph.D., said the company is "very excited" by the data and intends to move forward with phase 3 "as soon as possible."

While there are numerous treatments for the wet form of AMD, dry AMD with GA is currently an untreatable condition, according to David Boyer, M.D., of Retina-Vitreous Associates Medical Group, who said: "the reduction of the progression of atrophy in this trial offers new hope for vision maintenance for our patients." It's worth noting that dry AMD also accounts for 85% to 90% of all AMD cases, but tends to progress more slowly.

The new data are a big step toward fulfilling Apellis' ambition to develop a series of indications for its C3 inhibitor beyond PNH in a market currently monopolized by mid-cap biotech Alexion's C5-targeting Soliris (eculizumab), which made its debut way back in 2003.

In June, Apellis reported data from two phase 1b trials (PDF) of subcutaneous APL-2 in PNH that included patients who do not respond well to Soliris or develop anemia on Alexion's drug, showing improvements in a biomarker for efficacy as well as hemoglobin levels. It also reported data from three patients never treated with Soliris. Armed with those data, Apellis is planning to advance the drug into phase 3 for PNH before the end of the year.

The market opportunity for APL-2 in both AMD and PNH could be sizable. Alexion is predicting Soliris sales of more than $3 billion this year in PNH and second indication atypical hemolytic uremic syndrome (aHUS). The company has, however, trimmed back its forecasts in the wake of a tricky period punctuated by R&D setbacks—including somewhat disappointing data for Soliris in myasthenia gravis—and an internal probe into fraud allegations.