#AAN2018 — Investigational Pompe Therapy ATB200/AT2221 Shows Promising Results in Phase 1/2 Trial

Interim results a from Phase 1/2 clinical trial support the therapeutic benefits of investigational therapy combination ATB200/AT2221 in patients with Pompe disease.

Participants in the study showed improvements in motor and respiratory function. The therapy also resulted in a durable decrease of muscle damage biomarkers.

These results will be presented at the upcoming 2018 Annual Meeting of the American Academy of Neurology on April 24 in Los Angeles in the Advances in Muscular Dystrophy and Congenital Myopathy session. The presentation is titled “First-in-human Study of ATB200/AT2221 in Patients with Pompe Disease: Preliminary Results From the ATB200-02 Trial.”

ATB200/AT2221, developed by Amicus Therapeutics, is a recombinant (lab-made) human acid alpha-glucosidase (GAA) enzyme (ATB200), administered with a small molecule pharmacological chaperone (AT2221).

An ongoing, open-label Phase 1/2 clinical trial (NCT02675465) is investigating ATB200/AT2221 as a potential therapy for late-onset Pompe disease.

In particular, researchers are assessing the therapy’s safety and effectiveness when administered over an 18-week treatment period followed by a long-term extension study. The study will also assess pharmacokinetics (the therapy’s movement in the body) and pharmacodynamics (the therapy’s effects on the body).

The trial enrolled 20 patients, 15 of whom had previously been treated with enzyme replacement therapy (ERT) — 11 patients who were able to walk 200 to 500 meters in the six-minute walk test (cohort 1) and four patients who were in wheelchairs (cohort 2). The remaining five patients were able to walk but had never been treated with ERT (cohort 3).

In the first phase of the trial, patients received single ascending doses of intravenously infused ATB200 to assess the therapy’s tolerability.

Interim results showed that combining ATB200 with AT2221 significantly increased the mean levels of the GAA enzyme and its activity, measured at 12 and 24 hours after administration. Also, GAA protein half-life — the time it takes to lose half of its pharmacologic activity — increased by approximately 28.6% with the combination therapy, compared with just ATB200.

Administering ATB200 with AT2221 also decreased markers of muscle damage (creatine kinase, alanine aminotransferase, and aspartate aminotransferase) and halted the accumulation of hexose tetrasaccharide (Hex4), a biomarker of the disease.

At nine months after beginning the study, patients experienced increases in the distance they were able to walk in the six-minute walk test by 37.2 meters in cohort 1 and 74.9 meters for cohort 3. Improvements were also seen for other motor function tests. Cohort 2, patients in wheelchairs, showed increases in upper extremity strength.

Respiratory function measured by forced vital capacity increased in cohort 3 and was maintained in cohort 1.

These interim results “indicate that next-generation ATB200/AT2221 has the potential to be an important treatment option for patients with Pompe disease. Further data from this study are forthcoming,” the researchers concluded.