Rare Disease Report

Explaining the New Safety Data for neoGAA in Late-Onset Pompe

FEBRUARY 22, 2018
Mathew Shanley
At the 14th WORLDSymposium in San Diego earlier this month, Sanofi Genzyme announced the presentation of new safety data for investigational avalglucosidase alfa (neoGAA) in patients with late-onset Pompe disease.

After the event, Rare Disease Report spoke with Loren D.M. Pena, M.D., Ph.D., Associate Professor of Pediatrics at Duke University School of Medicine, who presented the data.

Rare Disease Report: What was the data that was presented at WORLDSymposium?

Loren D.M. Pena, M.D., Ph.D.: We presented the data for the initial phase of neoGAA along with the extension. This is a long-term safety study along with the repeat dosing of avalglucosidase alfa in late-onset Pompe disease patients, and the extension has been going on for over 3 years. We presented the data for about 3-and-a-half years of treatment. The study started as the evaluation of safety, tolerability and pharmacokinetics of repeat dosing of avalglucosidase alfa, which is a second-generation replacement therapy for Pompe disease.

RDR: How long did take before patients were enrolled into the extension portion of the study? How many people are currently enrolled in the extension study?

Pena: That initial study went on for about 6 months or so and then after that, the patients were able to enroll into the extension study. Right now, there are about 18 patients with late-onset Pompe disease who have been treated for about 3-and-a-half years with this repeat dosing. In the initial phase, there were 3 dosages: 5, 10, or 20 mg for each infusion. At the end of the initial study period patients would roll over into the extension which would receive 20mg/kg of avalglucosidase alfa.

RDR: Obviously, the presentation at WORLDSymposium focused on a safety profile, but what are the primary and secondary endpoints of this study?

Pena: Some of the primary endpoints were, of course, safety because this is a first Phase 1 study so that included adverse events, treatment-emergent adverse events, physical exam, vital signs, lab evaluations, and [electrocardiograms]. Then some of the secondary endpoints were related to pharmacokinetics and pharmacodynamics. We did have some exploratory endpoints with the small study: the number of patients participating which is important for an early phase study, these endpoints were pretty exploratory.

RDR: When working with any rare disease, there are small patient populations. Did you have any issues enrolling patients?

Pena: The study was fully enrolled. The initial study had 21 spots and all of them were filled. There were 2 study groups enrolled, so there was a naïve group and then there was what call a “switch group.” These were patients with late-onset Pompe disease who have been treated the standard of care and patient therapy for at least 9 months. We had 3 patients who discontinued treatment; one of them experience a serious adverse event and 2 of them had personal reasons for discontinuation. Those patients were replaced, so a total of 24 patients were treated when the original enrollment was for 21.

We talk about patient disposition; right now, there are about 19 patients enrolled in the study. Eighteen of them are ongoing patients, and one patient discontinued due to personal reasons that were not related to any event during the study.

RDR: What kind of adverse events or infusion-associated reactions were reported in patients who received neoGAA?

Pena: In terms of adverse events, the severity was rated as generally mild across all the drug levels in the initial study. There was one serious adverse event that was also rated as an infusion-associated reaction and that was respiratory distress and chest discomfort during the infusion for one of the patients. Then several other serious adverse events happened that were deemed to not be associated with the investigational product. There were no deaths or life-threatening adverse events reported so far. It’s a pretty reassuring safety profile.

Going over the infusion-associated reactions, some of the reported reactions were rash, flushing, headache, and so in general, the infusion-associated reactions were in the range of what we have experienced with first generation with commercial treatment. So, the specific infusion associated reactions were not out of the ordinary for enzyme replacement therapy. The safety profile was generally mild adverse events across all levels of the initial study. There was one discontinuation out of the 24 that was deemed to be related to an infusion. The rest of the discontinuations were due to personal reasons, there weren’t any deaths or life-threatening serious adverse events. The safety profile was really reassuring for avalglucosidase alfa and consistent with what we saw in the initial 6 months of the phase 1 study.

RDR: What are the next steps as you take the data that was presented at WORLDSymposium and you move forward with it?

Pena: This is an ongoing study that’s planned for up to 6 years, so we probably have a couple more years to acquire study data. There’s also an ongoing study that is actively recruiting called COMET (NCT02782741) and we can get you the clinical trial registration number for that study. It is a double blind, active study between standard of care and avalglucosidase alfa so patients are randomized into either arm for up to a year of treatment and then they can enroll in an extension of that for avalglucosidase alfa. So that should satisfy some of the interest in the community for how avalglucosidase alfa compares to the commercial therapy.


For more from WORLDSymposium and other conferences breaking the latest in the rare disease community, follow Rare Disease Report on Facebook and Twitter.

Copyright © RareDR 2013-2018 Rare Disease Communications. All Rights Reserved.