Enter Note
Authors: Presenting Author: Renzo Guerrini, MD, PhD – Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, University of Florence, Florence, Italy.
Benjamin Serraz, Pharm.D, PhD – Biocodex, Orphan Disease Division (HQ), Gentilly, France; Laurent Chancharme, Pharm.D, PhD – Biocodex, R&D department, Compiègne, France; Catherine Chiron, MD, PhD – APHP, Necker-Enfants Malades Hospital, Pediatric Neurology and Reference Center for Rare Epilepsies, Paris, France
Poster Number: 2.444
Rationale:
Dravet syndrome is a rare form of developmental and epileptic encephalopathy, initially described by Charlotte Dravet in 1978. Almost 30 years later, in 2007, stiripentol (STP) was the very first anti-seizure medication approved for Dravet syndrome (DS) based on two placebo-controlled randomized clinical trials: STICLO France and STICLO Italy, pioneers in paediatric epilepsy. While data already published (Chiron et al., 2000; Guerrini R. et al., 2004) are still relevant for today’s clinical practice (e.g., ≥ 50% responder rate), new standards have now emerged. Therefore, we investigated for the first-time new STP data from the STICLOs trials, notably from open-label extension periods (OL) and on quality of life (QoL).
Methods:
After a two month-blind period (2m-blind), patients could continue during an OL (one month) without breaking the blind, where placebo (PBO) patients switched to STP (‘OL-PBO’), and STP patients continued treatment. All along the trials, STP was titrated at 50 mg/kg/d. Data from both STICLO studies were pooled and percentage change from baseline in generalized tonic-clonic seizure frequency (%-change-GTCSF), responder rates (≥50% & ≥75% seizure frequency reduction) and seizure freedom were calculated. QoL was assessed via the longest period of consecutive seizure-free days (CSFd) from patient dairies.
Results:
A total of 64 patients were included during the 2m-blind (STP 33, PBO 31), 43 during the OL and 53 patient diaries were collected. Median %-change-GTCSF significantly differed at the end of the 2m-blind (-84.4% vs -5.8%, p< 0.001, STP vs PBO), which was no longer the case at the end of the OL (-79.8% vs -81.4%, p=0.7, OL-STP vs OL-PBO). Similarly, ≥50% responder rates were 71.9% vs 6.9% (p< 0.001, STP vs PBO) and 74.1% vs 87.5% (p=0.4, OL-STP vs OL-PBO) at the end of the 2m-blind and OL periods, respectively. Also, ≥75% responder rates were 56.3% vs 3.4% (p< 0.001, STP vs PBO) and 59.3% vs 68.8% (p=0.5, OL-STP vs OL-PBO) on the same periods, correspondingly. As for seizure freedom, no PBO patients achieved this outcome, while 37.5% did in the STP group (p< 0.001) at 2m-blind. However, during the OL period, no difference was observed between groups (37.0% vs 25.0%, p=0.4, OL-STP vs OL-PBO). Finally, median CSFd was significantly higher (p< 0.001) for STP (32.5 days) versus PBO (8.0 days) groups at the end of the 2m-blind period.
Conclusions:
New analyses of the STICLO clinical trials confirm the high efficacy maintained over time of STP in reducing GTCS frequency. STP displays significant improvement in term of seizure free days, which has been correlated to a higher QoL of DS patients and their caregivers.
Funding:
This study was supported by Biocodex.
Benjamin Serraz, Pharm.D, PhD – Biocodex, Orphan Disease Division (HQ), Gentilly, France; Laurent Chancharme, Pharm.D, PhD – Biocodex, R&D department, Compiègne, France; Catherine Chiron, MD, PhD – APHP, Necker-Enfants Malades Hospital, Pediatric Neurology and Reference Center for Rare Epilepsies, Paris, France
Poster Number: 2.444
Rationale:
Dravet syndrome is a rare form of developmental and epileptic encephalopathy, initially described by Charlotte Dravet in 1978. Almost 30 years later, in 2007, stiripentol (STP) was the very first anti-seizure medication approved for Dravet syndrome (DS) based on two placebo-controlled randomized clinical trials: STICLO France and STICLO Italy, pioneers in paediatric epilepsy. While data already published (Chiron et al., 2000; Guerrini R. et al., 2004) are still relevant for today’s clinical practice (e.g., ≥ 50% responder rate), new standards have now emerged. Therefore, we investigated for the first-time new STP data from the STICLOs trials, notably from open-label extension periods (OL) and on quality of life (QoL).
Methods:
After a two month-blind period (2m-blind), patients could continue during an OL (one month) without breaking the blind, where placebo (PBO) patients switched to STP (‘OL-PBO’), and STP patients continued treatment. All along the trials, STP was titrated at 50 mg/kg/d. Data from both STICLO studies were pooled and percentage change from baseline in generalized tonic-clonic seizure frequency (%-change-GTCSF), responder rates (≥50% & ≥75% seizure frequency reduction) and seizure freedom were calculated. QoL was assessed via the longest period of consecutive seizure-free days (CSFd) from patient dairies.
Results:
A total of 64 patients were included during the 2m-blind (STP 33, PBO 31), 43 during the OL and 53 patient diaries were collected. Median %-change-GTCSF significantly differed at the end of the 2m-blind (-84.4% vs -5.8%, p< 0.001, STP vs PBO), which was no longer the case at the end of the OL (-79.8% vs -81.4%, p=0.7, OL-STP vs OL-PBO). Similarly, ≥50% responder rates were 71.9% vs 6.9% (p< 0.001, STP vs PBO) and 74.1% vs 87.5% (p=0.4, OL-STP vs OL-PBO) at the end of the 2m-blind and OL periods, respectively. Also, ≥75% responder rates were 56.3% vs 3.4% (p< 0.001, STP vs PBO) and 59.3% vs 68.8% (p=0.5, OL-STP vs OL-PBO) on the same periods, correspondingly. As for seizure freedom, no PBO patients achieved this outcome, while 37.5% did in the STP group (p< 0.001) at 2m-blind. However, during the OL period, no difference was observed between groups (37.0% vs 25.0%, p=0.4, OL-STP vs OL-PBO). Finally, median CSFd was significantly higher (p< 0.001) for STP (32.5 days) versus PBO (8.0 days) groups at the end of the 2m-blind period.
Conclusions:
New analyses of the STICLO clinical trials confirm the high efficacy maintained over time of STP in reducing GTCS frequency. STP displays significant improvement in term of seizure free days, which has been correlated to a higher QoL of DS patients and their caregivers.
Funding:
This study was supported by Biocodex.