Apellis resumes phase 3 AMD trials after addressing safety issue

Green traffic light
The two 600-patient phase 3 trials are on track to be fully enrolled around this time next year. (CC0/Public Domain)

Apellis Pharmaceuticals has resumed dosing in phase 3 trials of its treatment for an advanced form of age-related macular degeneration (AMD). The resumption follows modifications to the production process to cut the risk of the noninfectious inflammation that triggered the halt.

Dosing in the phase 3 geographic atrophy program began in September only to stop in October after reports of eight cases of noninfectious inflammation in patients who received Apellis’ APL-2. The two phase 3 trials are designed to show APL-2 reduces the area of geographic atrophy lesions by binding to C3 and C3b and thereby inhibiting the complement cascade. But the adverse events put the brakes on those plans.

Apellis suspected the adverse events were isolated to a single lot of APL-2 and voluntarily stopped the study and initiated an investigation to confirm its thinking. Apellis originally targeted a 2018 restart for the trials.

Training Course

BioBasics: Biotech For The Non-Scientist

BioBasics: Biotech for the Non-Scientist is a two-day course for those who want to better understand the science driving the industry. The course starts with basic scientific concepts and quickly delves into the causes of genetic and infectious disease and the therapeutic strategies used to mitigate disease. The latest innovations in immunotherapies, gene therapy, checkpoint inhibitors, CAR-T and more are explained.

That goal came and went as the investigation led Apellis to modify its manufacturing processes to eliminate an impurity it thinks was introduced during scale-up. Apellis fingered the impurity as the likely cause of the inflammation and took action to prevent its production.

Investigators in a phase 1b geographic atrophy trial have given the resulting APL-2 products to 10 patients without incident. The lack of adverse events encouraged Apellis to resume dosing in the phase 3 using the stockpile of APL-2 it has accrued. Apellis thinks it has enough APL-2 made using the new process to cover the rest of the phase 3 program.

The two 600-patient trials in the phase 3 program are on track to be fully enrolled around this time next year. With the primary endpoint assessing patients at 12 months, the timeline means Apellis is still some way from having phase 3 data. But recent events have put it in a better position to make the hike toward the pivotal readout. 

News of the resumption of the phase 3 program comes days after Apellis struck a deal with SFJ Pharmaceuticals, a drug development shop backed by Blackstone Life Sciences and Abingworth. The novel deal secured Apellis $60 million upfront and up to $60 million in near-term milestones to fund development of APL-2 in paroxysmal nocturnal hemoglobinuria, enabling it to continue advancing on multiple fronts without raising money from investors.

Shares in Apellis rose 30% in the days following news of the SFJ agreement.

Suggested Articles

Flagship Pioneering has raised $824 million for a fund to support biotech and health companies that have come up through its Flagship Labs foundry.

The FDA’s warning letters to breast implant manufacturers come during newly galvanized agency probes into the long-term safety of silicone implants.

At the annual meeting of the American College of Cardiology this week, a new analysis of Merck’s anacetrapib cast a shadow on DalCor’s hypothesis