Sep 19 · The PII/PIII trial DEVOTE (NCT04089566) has been planned to compare a higher dose (28mg) to the currently licensed dose (12mg) in spinal muscular atrophy. The trial will enrol 126 patients. It is expected that the trial will complete in June 2022 .
Jul 19 · New results from the NURTURE study in pre-symptomatic infants spinal muscular atrophy (SMA) (n=25). After up to 45.1 months of analysis, spiranza continues to demonstrate efficacy and safety in these pts who were treated pre-symptomatically in comparison to the natural history of this disease .
Feb 18 · Results of PIII CHERISH study (NCT02292537) published in NEJM. Trial (n=126) found intrathecal nusinersen was associated with an improvement in HFMSE score at 15 months (least-squares mean difference in change from baseline of 5.9 points vs sham; 95% CI 3.7 to 8.1; P<0.001) .
Nov 16 · In the PIII Cherish study, children taking nusinersen showed a highly statistically significant clinically meaningful improvement in motor function vs. those who did not receive treatment, as measured by the Hammersmith Functional Motor Scale Expanded points scale. From baseline to 15 months of treatment, patients who received Spinraza achieved a mean improvement of 4 points, while patients who were not on treatment declined by a mean of 1.9 points. Patients can now move over to its Shine open-label extension study .
Aug 16 · Ionis and Biogen announce that the pre-specified interim primary endpoint of the ENDEAR study (NCT02193074) has been reached, with an acceptable safety profile; as a result, the trial will be stopped and all participants will be able to transfer to the SHINE follow-up study .
Jan 16 · Ionis announce that recruitment to NCT02193074 (CHERISH) has reached the enrolment target, and that approximately 117 participants will be evaluated .
Nov 15 · Isis Pharmaceuticals begins an open-label extension study (SHINE; NCT02594124), enrolling 274 patients in the US. Primary outcome is safety and data collection should complete in Feb 2020 .
Jun 15 · Isis pharmaceuticals provided an update on its ongoing open-label PII clinical study (n=20) of ISIS-SMN Rx in infants with Type I SMA. The median event-free age increased for infants in both dosing cohorts, from 16.3 months to 19.9 months for the 4 infants in the 6 mg cohort, and from 11.6 months (n=12) to 16.7 months (n=15) for the infants in the 12 mg cohort. Muscle function scores increased from baseline and infants achieved motor milestones since their baseline evaluations. Only a single event has occurred, one infant in the 12 mg cohort required permanent ventilation. There have been no deaths since the previous analysis. The safety and tolerability profile of ISIS-SMNRx to date continues to support further development .
Nov 14 · Second pivotal PIII study, CHERISH (NCT02193074), initiated. CHERISH is a randomised, double-blind, sham-procedure controlled 15 month study in approximately 120 children aged 2-12 who are non-ambulatory with SMA. Pts will be randomised 2:1 to receive ISIS-SMN Rx or a sham procedure control. Efficacy and safety of a 12 mg dose of ISIS-SMNRx will be evaluated with a primary endpoint of change in the Hammersmith Functional Motor Scale-Expanded (HFMSE), a validated method to measure changes in muscle function in patients with SMA. The study is due to complete in June 2017 .
Oct 14 · In a PII study in 20 infants with SMA, in the 6 mg cohort: there have been two events (one accidental death and one permanent ventilation); median event-free age is 16.3 months. In the 12 mg cohort: median event-free age is 11.6 months; of the 12 infants, nine are alive without the need for permanent ventilation .
Aug 14 · P3 ENDEAR study (NCT02193074) initiated. ENDEAR is a randomised, double-blind, sham-procedure controlled thirteen month study in approximately 110 infants diagnosed with SMA. The study will evaluate the efficacy and safety of a 12mg dose of ISIS-SMNRx with a primary endpoint of survival or permanent ventilation. Additional efficacy endpoints are also included in the study. Estimated primary completion date (final data collection date for primary outcome measure) is June 2017 [4,5].
Feb 14 · Interim results from an open-label, multiple dose study (3, 6 and 9mg) showed that children on highest dose experienced an average increase of 3.7 points in muscle function score. An increase in SMN protein was also observed. Children going on to the extension study will be given a maintenance dose of 12mg every six months. Interim results on a further PII open label, multiple dose study in infants with SMA showed that all four infants in the 6mg cohort remained in the study for more than six months and are now 9.5 to 16 months old. All four are alive with none requiring permanent respiratory assistance .
Feb 14 · Severity of SMA correlates with amount of SMN protein. SMN is critical to the health and survival of nerve cells in the spinal cord responsible for neuromuscular growth and function. Infants with Type I SMA (most severe form) produce very little SMN protein and have a life expectancy of < 2years. Children with Type II (most common form) have more SMN protein but still have a shortened lifespan and are never able to stand independently. Children with Type III have a normal lifespan but accumulate life-long physical disabilities as they grow .
Feb 14 · NCT01839656 is an open-label, dose-escalation phase 2 sutdy in infants (age 3 weeks - 7 months) with Type I SMA. All infants from the 6 mg dose cohort have completed the three initially scheduled doses and, under the amended protocol, are eligible to receive an additional 12 mg dose six months after their initial three scheduled doses .
Feb 14 · Phase II Study NCT01703988 is an open-label, dose-escalation study designed to assess the safety, tolerability and pharmacokinetic profile of ISIS-SMNRx in children with Type II and Type III SMA. All children have been dosed in the initial three cohorts (3 mg, 6 mg and 9 mg) and the first has been dosed in the 12 mg cohort. The open-label extension study is designed to provide a single additional dose of 12 mg (n> 50 aged 2-15 yrs who have completed dosing with ISIS-SMNRx in other studies) .