The Drug Development Process > Phase II clinical trials with Reldesemtiv in Patients with Spinal Muscular Atrophy (SMA II-III)

presented in an oral presentation by John W. Day, MD, Ph.D., Professor of Neurology and Paediatrics (Genetics), Stanford University.

This hypothesis-generating study met its primary goal. It fulfills the effect and safety profile.

In collaboration with Astellas, Cytokinetics is developing reldesemtiv as a potential treatment for people with SMA and certain other debilitating diseases and conditions associated with skeletal muscle weakness and/or fatigue.

The study showed dose- and concentration-dependent increases in time to muscle fatigue as measured by changes from baseline in Six Minute Walk Distance (6MWD), a sub-maximal exercise test of aerobic capacity and endurance, and Maximal Expiratory Pressure (MEP), a measure of strength of respiratory muscles, after eight weeks of treatment with reldesemtiv.

The study enrolled 70 patients, 39 in Cohort 1 and 31 in Cohort 2. Ambulatory and non-ambulatory (Type II or Type III) patients 12 years of age and older were randomized 2:1, stratified by ambulatory ability, to receive reldesemtiv or placebo dosed twice daily for eight weeks. The first cohort of patients received 150 mg of reldesemtiv or placebo and the second cohort received 450 mg of reldesemtiv or placebo twice daily. Enrollment in this study was stopped short of the targeted 72 patients after blinded analyses of the variability around the changes from baseline of several efficacy measures demonstrated that the study had sufficient statistical power to detect clinically relevant differences versus placebo in efficacy endpoints with the 70 patients already enrolled.

The study, which examined two dose levels of reldesemtiv, 150 mg or 450 mg twice daily, demonstrated dose-dependent increases in 6MWD in ambulatory patients as measured at both post-baseline time points, week four and week eight. In the 150 mg twice daily group, the increase vs. placebo was 10.86 meters (p=0.2531) after four weeks of treatment with reldesemtiv and 7.72 meters (p=0.4684) after eight weeks of treatment. In the 450 mg twice daily group, the increase vs. placebo was 35.63 meters (p= 0.0037) at week four and 24.89 meters (p= 0.0584) at week eight. There was also a statistically significant correlation between Cmax, or peak concentration of reldesemtiv, and change from baseline in 6MWD, with a slope estimate of 9.53 meters/(µg/mL). (p=0.0086).

The study also showed increases vs. placebo in MEP. In the 150 mg twice daily group, the increase in MEP was 5.95 cm H2O (p=0.2276) after four weeks of treatment with reldesemtiv and 11.69 cm H2O (p=0.0378) after eight weeks of treatment. In the 450 mg twice daily group, the increase in MEP compared to placebo was 9.17 cm H2O (p=0.0855) after four weeks of treatment with reldesemtiv and 13.15 cm H2O (p=0.0298) after eight weeks of treatment. Other assessments in the study, including the Hammersmith Functional Motor Score – Extended, Revised Upper Limb Module, Timed Up-and-Go and Forced Vital Capacity did not demonstrate meaningful differences between reldesemtiv versus placebo

Adverse events were similar between groups receiving reldesemtiv and placebo. The most commonly observed adverse effects were headache, constipation and nausea. Four patients had serious adverse events reported that resulted in early termination of study drug treatment, all considered to be unrelated to reldesemtiv.

 

Spinraza i Danmark: Medicinrådet ønsker markant laver pris som Sverige, Norge og Tyskland vi spekulerer på hvorfor!

Enig, det er også uforståeligt for os, at Medicinrådet forlanger markant lavere priser i Danmark end det man har forhandlet og accepteret i andre sammenlignelige lande som Norge og Sverige, Tyskland og Schweiz.”

Det er pinligt, at Danmark ikke giver denne banebrydende medicin til sine SMA patienter

  1. Lisbeth Koed DoktorNår små diagnoser møder det store system
  2. Muskelsvindfonden Medicinrådet drøfter igen Spinraza – dog kun som orienteringspunkt

Nya studieresultat bekräftar effekten med Spinraza vid SMA typ 2 eller 3

Sådan virker Spinraza – Hur verkar Spinraza

Efter varje storm kommer solen alltid. Positiva reaktioner kommer från Medicinrådet

Nya studieresultat bekräftar effekten med Spinraza vid SMA typ 2 eller 3

Nya studieresultat bekräftar effekten med Spinraza vid SMA typ 2 eller 3. NURTURE studier utförda med SPINRAZA-behandlade ungdomar/ unga vuxna med SMA typ 2 och 3 (17-19 år) visade stabil eller förbättrad motorfunktion och förbättrad livskvalitet
CAMBRIDGE, Mass.–(BUSINESS WIRE)–Biogen (Nasdaq: BIIB) today announced new interim Phase 2 results from NURTURE, the ongoing open-label, single-arm study evaluating the efficacy and safety of SPINRAZA® (nusinersen) among pre-symptomatic infants with spinal muscular atrophy (SMA). In NURTURE, all infants treated with SPINRAZA were alive, did not require permanent ventilation and showed improvement in motor function and motor milestone achievements as of July 5, 2017, compared to the disease’s natural history. This study, along with a case series demonstrating SPINRAZA’s effectiveness among teens and young adults, will be presented at the Muscular Dystrophy Association (MDA) Clinical Conference on March 11-14, 2018, in Arlington, Virginia.

“These results reinforce SPINRAZA’s effectiveness as the first and only approved treatment for SMA and demonstrate once again the benefit it can bring to individuals with SMA, including infants, teens and young adults,” said Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen. “SPINRAZA is supported by the largest well-controlled SMA clinical development program conducted to date and we are committed to ongoing research in SMA. Biogen looks forward to working with healthcare providers and institutions in order to provide teens and young adults with SMA access to SPINRAZA, a treatment that has demonstrated significant benefit in the maintenance of motor function for these patients.”

Nya kliniska studier: Spinraza förbättrar motor och respirator funktion vid SMA-barn,

An early treatment with Spinraza improves motor function of patients with spinal muscular atrophy

Neue Resultate aus der NURTURE Studie mit Spinraza bei Kinder, Teenager und junge Erwachsene, zeigt Verbesserungen der motorischen Funktionen

Diese Resultate dürften die letzten Kritiker zum schweigen bringen. Biogen publizierte ihre neusten Forschungsergebnisse auf der letzten Muscular Konferenz in Virginia. Kinder, Teenager und heranwachsenden Jugendliche mit SMA Typ II und III zeigen eine deutliche Verbesserung ihrer motorischen Funktionen.

These results reinforce SPINRAZA’s effectiveness as the first and only approved treatment for SMA and demonstrate once again the benefit it can bring to individuals with SMA, including infants, teens and young adults”

In the NURTURE study, SPINRAZA was administered to infants six weeks old or younger (n=25), who were in the pre-symptomatic stage, genetically-diagnosed with SMA and had two or three copies of the SMN2 gene (n=15 for two copies (most likely to develop Type 1 SMA); n=10 for three copies (most likely to develop Type 2 SMA)). At the time of this interim analysis, infants had been followed for up to 25.6 months – well beyond the typical timeframe when most infants with Type 1 SMA would have required permanent ventilation or died. The interim analysis, titled, “Nusinersen in Infants Who Initiate Treatment in a Pre-Symptomatic State of SMA: Interim Efficacy and Safety Results from the Phase 2 NURTURE Study,” showed that all infants were alive and none required tracheostomy or permanent ventilation.