Roche Pharmaceuticals Angelman Syndrome Program Update to the FAST Community
Roche Pharmaceuticals provided an update on their Angelman Syndrome Program at the 2021 FAST Science Summit. The program has been ongoing for seven years and includes collaborations with ABOM, Ionis, and Biogen. The program consists of the FREESIAS observational study and the TANGELO Phase 1 drug study. The FREESIAS study, which enrolled individuals with Angelman Syndrome and typically developing controls, has been completed and the results will be published in 2022. The TANGELO study is currently ongoing and aims to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of the drug UBE3A-LNA in participants with Angelman Syndrome. The study has enrolled 43 participants and is expected to continue until 2022. Adverse events in the study have been monitored and managed, with fever and vomiting being the most common side effects. After the completion of TANGELO Phase 1, participants will have the opportunity to continue into the TANGELO Long-Term Extension. Caregivers are reminded of their responsibilities during the study, including attending visits, providing feedback, and maintaining confidentiality.
Good morning, good afternoon, and good evening, everyone. It’s a pleasure to be part of the FAST Summit 2021, although only virtually, unfortunately. I hope that you and your families are all doing well, and hopefully the situation will improve next year so that we will be able to meet in person. My name is Brenda Vincenzi, I’m the Senior Medical Director for the Angelman Syndrome Program at Roche. Today I guide you through a brief history and progress for the Angelman Syndrome Program at Roche since FAST last year. We’ll give you a brief summary of where we stand with previous observational study, an update on TANGELO Phase 1 drug study, and I will introduce the TANGELO long-term extension part of the study.
History and Progress
So what comes after TANGELO Phase 1 drug study part 1? We’ve been working within the Angelman Syndrome community for the past seven years. We started back in 2015 by listening and learning from the Angelman Syndrome community. We then developed, together with ABOM, the disease concept model that is now published in 2018 and 2019 in partnership with Ionis and Biogen. We started the co-creation of FREESIAS’s observational study. Recruitment for FREESIAS started in 2019 when we also started to prepare for the start of Phase 1 TANGELO drug study at Roche. In 2020, in August, we started recruitment for TANGELO, and in 2021, FREESIAS was completed.
FREESIAS Observational Study
FREESIAS is an endpoint enabling study in Angelman Syndrome. Study sponsors Roche and Genentech, co-founded with Biogen and Ionis. FREESIAS is a non-drug observational endpoint enabling study with a particular decentralized design, meaning, as you can see here from the picture, that there are only two in-clinic visa. And we explore new digital approaches or digital biomarkers, as you can see represented here, for example, from the EEG at home, the sleep map, and others. Primary objectives of FREESIAS are the feasibility and value of novel endpoints and biomarkers to inform clinical trial design. We enrolled 43 individuals with Angelman Syndrome, age 1 to 12, 12 individuals with Angelman Syndrome, age 18 and above, 20 typically developing controls, age 1 to 12, and the study was run only in the U.S. and was completed in May 2021. The main study results are currently being prepared for publication and will be presented and shared with the Angelman Syndrome community next year in 2022.
TANGELO Phase 1 Drug Study
TANGELO is an open-label, multi-center study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of our molecule called UBE3A-LNA in participants with Angelman syndrome. We are enrolling up to 66 individuals, both males and females, age 1 to 12, that present with either mutation or deletion genotypes. We have four countries included in TANGELO, the U.S., the Netherlands, Spain, and Italy, with up to 15 different sites. Study duration, we started in August 2020, and we continue for approximately 58 weeks. TANGELO is an open-label, meaning that all participants, all individuals enrolled in the study, receive the study medication, up to three escalating doses. It’s a multi-center study. There are different centers in the U.S. and Europe, with an adaptive, multiple ascending, intra-participant dose escalation. So each participant will receive two to three escalating doses on the drug. The primary objective of TANGELO, Phase 1 drug study, are safety and tolerability of the drug. The secondary objectives are the PK, PD, pharmacokinetics, pharmacodynamics, and efficacy.
TANGELO Recruitment Update
We started enrollment back in August 2020. We completed enrollment for the 5 to 12 individuals with Angelman syndrome that here are presented by cohort A in yellow. And cohort Blue, the blue cohorts called B for the 1 to 4 individuals with Angelman syndrome, are proceeding. We are fully enrolled up to B3. And in total, we enrolled, if you consider B and A cohort, we enrolled 43 participants with Angelman syndrome. All participants are still enrolled, so there are no what we call dropouts. And the good news is that we can proceed with enrolling patients in the B cohort in the US starting at the beginning of 2022.
Adverse Events in TANGELO
Participants in TANGELO have been clearly monitored for drug and non-drug related adverse events. Some, not all, but some participants presented with some fever and or vomiting a few days after receiving the drug through injection. Fever and vomiting are manageable with over-the-counter medication to control fever and antiemetic medication for nausea and or vomiting. Fever and vomiting are solved in a few days without any sequelae. All patients that presented with some fever and or vomiting are doing well. Review of safety data is continuous and ongoing to facilitate the detection of potential safety signals from the study treatment for efficacy, risk assessment, and determination of the benefit-risk relationship.
TANGELO Long-Term Extension
After the TANGELO Part 1, we proceed with what we call TANGELO Long-Term Extension. In this Long-Term Extension, all participants that were part of the TANGELO Phase 1 will have the
- Title: Roche Pharmaceuticals Angelman Syndrome Program Update to the FAST Community
- Author(s): Brenda Vincenzi
- Author(s)’ affiliation: Roche Pharmaceuticals
- Publication date: 2022-01-04
- Collection: 2021 FAST Science Summit