SMA Europe Workshop

13 - 14 Jul 2012

Rome, Italy

Mapping out Opportunities and Challenges for SMA clinical trials

This focused expert workshop, organised by SMA Europe, was a brainstorming meeting that aimed to engage all participants, (scientists, clinicians, physical therapists, industry, patients and patient organisations) to address and propose practical initiatives to be implemented to overcome key bottlenecks in clinical trials for SMA. 31 participants from Europe and the US presented and discussed past, ongoing and future clinical trials and key challenges facing the implementation of clinical trials for SMA in Europe and in the US, with particular attention to the needs and specifics related to the SMA population subtypes and the population age. Each session was followed by intensive discussion and conclusions.

Most importantly, the participants agreed to work out a protocol for outcome measures for each SMA type. There was also agreement on possible inclusion criteria and outcome measures to be used in possible clinical trials in each SMA type.

Based on experience in preclinical trials in animal models which show a more substantial effect when treatment is started early, there was extensive discussion over the question of starting human trials in very young infants and even in the “presymptomatic” stage. However, the many challenges to this approach were also highlighted, including the lack of data on whether the experience in animal models is in fact transferrable to the human situation, the many ethical questions surrounding trials in infants, the difficulty predicting the future severity of the condition from genetic data alone, and the difficulty recruiting “presymptomatic” patients in the absence of neonatal screening. Although in both Europe and the US, patient registries are being utilised for recruitment of older patients for research studies (such as the Trophos trial in Europe), individuals with type 1 SMA are underrepresented in all current registries (making up an average of 25% of the registered SMA population despite an expected incidence of around 60% of cases). In the US a neonatal screening pilot program is being initiated in two states with the possibility to include infants identified in this manner in natural history studies and clinical trials. It was concluded that a similar pilot neonatal screening initiative should be explored for Europe and that patient organisations may play an important role in moving this forward, as it will face significant hurdles to implement and regulations differ from country to country.

A further area where it was felt that the SMA Europe could play an important role is in discussions with regulatory authorities, building on the positive experience of previous initiatives where consensus opinion meetings involving patient groups, researchers, industry and clinical experts have been welcomed by the EMA and the FDA. These include collaborative efforts led by the International Coordinating Committee (ICC) for SMA and meetings organised under the auspices of TREAT-NMD on SMA outcome measures (2007) and antisense approaches in DMD (2009) - which may also be of interest in SMA in future. With the recent developments in the field, it was concluded that it is timely to approach the regulators again, and not only the patient groups and academics but also the industry participants present during this workshop saw the benefits of a united approach to discuss key questions.

The participants recognized the need to meet on a regular basis in order to investigate the progress made in the field and how this progress can be efficiently turned into clinical trials.

Following the main workshop, a satellite meeting organised by TREAT NMD and funded by Telethon, involving the participants of the main workshop with experience on outcome measures, provided an excellent opportunity to discuss the results of the recent Rasch analysis and further plans for harmonization of outcome measures across the US and Europe.

A complete meeting report will be available via the SMA Europe website in due course.

Report by Brunhilde Wirth and Eugenio Mercuri

A. Ambrosini (Fondazione Telethon, Italy)
JL. Abitbol (HRA Pharma, previously Trophos, France)
M. Azzouz (University of Sheffield, UK)
M. Barkats (Institute of Myology, France)
C. Béroud (Inserm, France)
E. Bertini (Bambino Gesu Childrens research Hospital, Italy)
K. Bishop (Isis Pharmaceuticals, USA)
A. Burghes (Ohio State University, USA)
K. Chen (SMA Foundation, USA)
B. Estournet (Hôpital Raymond Poincaré, France)
R. Finkel (The Children’s Hospital of Philadelphia, USA)
B. Kaspar (Ohio State University, USA)
N. Kayadjanian (Consultant, France)
O. Khwaja (Roche, Switzerland)
J. Kissel (Ohio State University, USA)
S. Kolb (Ohio State University, USA)
K. Kroschell (Northwestern University USA)
A. Mayhew (Newcastle University, UK)
E. Mercuri (Catholic University, Italy)
P. Moore (SMA Europe, Italy)
F. Muntoni (Dubowitz Neuromuscular Centre, UK)
MC. Ouillade (AFM, France)
FM. Pradat (Pitié-Salpétrière Hospital, France)
P. Rippert (Hospices Civils de Lyon France)
F. Rouault (SMA-EUROPE, France)
I. Schwersenz (SMA-EUROPE, Germany)
K. Talbot (Oxford University, UK)
R. Thompson (Jennifer Trust, UK)
FD. Tiziano (Catholic University, Italy)
E. Tizzano (Hospital Sant Pau, Spain)
L. Viollet (University of Utah, USA)
T. Voit (Institute of Myology, France)
M. Will (Freiburg University, Germany))
B. Wirth (University of Cologne, Germany)

The workshop was kindly sponsored by the Foundation “Kindness for Kids” (Munich)