Case Study: developing a complex dosing drug schedule for a DART Pompe disease study

7 June 2021

Amics Therapeutics, based in Cranbury, NJ (USA), focuses on finding treatments for a range of devastating and rare and orphan diseases. Its lead biologics program is ATB200/AT2221, a uniquely engineered Pompe disease enzyme replacement therapy that will be administered in combination with a pharmacological chaperone and tested in multiple human genetic diseases.

A Short-Half Life Investigational Drug Suggests an Every-Other-Day Complex Dosing Regime

The dialogue between Amicus and us began at the 2017 Society of Toxicology conference and resulted in a large series of DART studies being awarded to us at its center for biotech excellence in Greenfield, IN. Early in the engagement, the most experienced US-based DART team member provided consultation on study design to make it more consistent with FDA guidelines and expectations.

The original proposed dosing interval may not have been tight enough to provide a robust assessment of developmental toxicity. Given the limited window of organogenesis (the period of highest sensitivity when organs are forming), and the short half-life of the investigational drug, the possibility existed that this embryo-fetal study would miss key exposure periods of organogenesis.

The subsequent recommendation of every-other-day dosing made the study considerably more challenging to execute, but also more likely to be viewed favorably by regulators. This senior level expertise made Amicus more comfortable with the revised design path.

Implementing the Dosing Regime

These studies involved highly complicated dosing protocols, including two oral administrations (antihistamine and a chaperone), followed by an infusion of the investigational drug. The three doses needed to be administered at precise (and narrow) time intervals.

According to the DART study director, “We had to become an orchestra to get everything dosed properly.”

In addition to the resource-intensive dosing, the project became further complicated by dosing changes, reprogramming the protocol and changing labels.

A Successful Biotech/CRO Partnership

As the program progressed to different species, a series of in-person meetings helped build understanding and trust. The dose range finding studies started smoothly, and the level of scientist involvement and technical expertise kept this extremely complex study on track.

For a small company with a limited number of pipeline assets, Amicus’s interest in and scrutiny of this project were high. Richie Khanna, PhD, was one of Amicus’s first employees, and she is currently Director of In Vivo Pharmacology and the principal investigator for the investigational drug’s bioanalysis: “These studies are so very important—everything is dependent on toxicology.”

“I never had any doubts in their capabilities,” Khanna notes. “They were on top of everything; transparent, accommodating, very responsive. It was exactly how I envisioned things should be with a partner.” After some initial bumps, “We developed a mutual trust and confidence that has continued throughout the engagement.”

Since kickoff, more than 60 staff members have touched this study. Amicus has since awarded four new juvenile DART studies to us, continuing its quest to find a cure for Pompe Disease and other human genetic diseases.

Download the full DART Pompe Disease Study PDF