Appearing in the same December 23 The Lancet issue as the recent publication of the latest preliminary data on the ASPIRO gene therapy trial (Astellas Pharmaceuticals), a comment entitled ‘Gene therapy for X-linked Myotubular Myopathy: the challenges’, (Voermans et al) highlights that important lessons should be learnt. You can read the comment in full here. The important lessons concluded by the authors were as follows:

(note: the emphasis in bolding has been added by the Myotubular Trust).

“First, promising outcomes in relevant animal models can raise false expectations because the model might not fully reflect the human phenotype. Therefore, all stakeholders should view the transferability of such findings to the clinical setting with extreme caution.

Second, the severity of hepatic involvement, and reports of myocarditis in ASPIRO and other gene therapy trials, shows the need to cooperate with a multidisciplinary array of specialists (eg, cardiologists, hepatologists, immunologists, pulmonologists, and intensivists), and should prompt preparation of an emergency protocol for optimal treatment of heart and liver failure, or other extramuscular complications, well before the start of a clinical trial.

Third, post-trial in-depth critical analysis of outcomes and suspected unexpected serious adverse reactions (SUSARs) is a pivotal step to accelerate therapeutic progress and reduce future risks in ultra- rare diseases. This process requires that all stakeholders communicate and discuss these sometimes sensitive data openly and constructively in a safe environment.

Fourth, it is crucially important that participants and their families are promptly informed about SUSARs by their study team, well before this information becomes available through other channels. Participation of European and North American patient organisations in future trial design would facilitate this process. 

Finally, a considerable emotional burden was associated with the outcomes of the ASPIRO trial, which not only affected the families of the children who died but also those of the survivors.”

Source: Nicol C Voermans, Ana Ferreiro, Annemieke Aartsema-Rus, Heinz Jungbluth; Gene therapy for X-linked myotubular myopathy: the challenges; Lancet Neurol. 2023 Dec