At the Annual SMA Conference, representatives from six of the seven programs currently in clinical trials gave an update on their programs.

Of these six programs, four—gene therapy, ISIS-SMNRx, RG7800, and LMI070—treat the underlying genetics of SMA. Gene therapy aims to correct the mutation in the SMN1 gene that causes SMA, and the other three programs address SMN2, the SMA “backup gene.” The other two programs, Olesoxime and CK-2127107, work to protect the muscles and nerves.

For more on the different phases of clinical trials, placebos, and other information on the clinical trial process, be sure to check out our new SMA clinical trials care series booklet. For visuals from this panel, including introductory presentations from Dr. Jill Jarecki, Cure SMA’s research director, and Dr. John Kissel, please visit our conference page.

Gene Therapy – Nationwide Children’s Hospital

A phase 1/2 clinical trial is underway testing gene therapy for Type 1 SMA patients. This therapy uses a virus (adeno-associated virus serotype 9) to deliver a normal copy of the SMN gene to a patient. This gene then expresses functional SMN protein in the motor neurons and other cells of the patient. Preclinical results and safety studies enabled an Investigational New Drug Application submitted to the Food and Drug Administration and opening of a clinical trial to administer the virus through a vein to Type 1 SMA patients. The clinical trial is taking place at Nationwide Children’s Hospital in Columbus, Ohio led by the Principal Investigator, Dr. Jerry R. Mendell. The first patient was dosed one year ago. To date, patients in the clinical trial have tolerated the treatment and early results are being evaluated. An additional clinical trial testing an intrathecal delivery of this same virus for Type 1 SMA patients is planned. The SMA gene therapy program is licensed to AveXis Inc.

CK-2127107 – Cytokinetics/Astellas

Single doses and multiple doses of CK-2127107 to steady state appeared safe and well-tolerated in healthy volunteers. Exposures increased generally proportionally across the dose ranges studied. CK-2127107 amplified the response of muscle to nerve activation following single doses of CK-2127107 administered to healthy volunteers, translating the results observed in preclinical models into humans. These data suggest that CK-2127107 may improve skeletal muscle function in patients with diseases characterized by skeletal muscle weakness and support the progression of CK-2127107 into Phase 2 clinical trials in patients with spinal muscular atrophy.

ISIS-SMNRx – Isis/Biogen

Isis is currently in collaboration with Biogen to develop and potentially commercialize the investigational compound, ISIS-SMNRx, to treat all types of SMA. ISIS-SMNRx is designed to alter the splicing of a closely related gene (SMN2) to increase production of fully functional SMN protein. The FDA granted orphan drug status and fast track designation to ISIS-SMNRx for the treatment of patients with SMA.

Isis is currently conducting two Phase 3 studies of ISIS-SMNRx. One Phase 3 study, ENDEAR, in infants with SMA and a second Phase 3 study, CHERISH, in children with SMA. The ENDEAR study is a randomized, double-blind, sham-procedure controlled thirteen month study in approximately 110 infants diagnosed with SMA. The study will evaluate the efficacy and safety of ISIS-SMNRx with a primary endpoint of event-free survival. The CHERISH study is a randomized, double-blind, sham-procedure controlled fifteen month study in approximately 120 non-ambulatory children with SMA. The study will evaluate the efficacy and safety of ISIS-SMNRx with a primary endpoint of a change in Hammersmith Functional Motor Scale-Expanded. For further study information, please visit and search for ISIS-SMNRx or the ENDEAR study (identifier number NCT02193074), the CHERISH study (identifier number NCT02292537), or visit the ISIS-SMNRx study site at

Biogen, in collaboration with Isis Pharmaceuticals, is working to develop Isis SMN-Rx for the treatment of Spinal Muscular Atrophy (SMA). This year, Biogen has started two additional studies in the Isis SMN-Rx clinical program, NURTURE & EMBRACE. The NURTURE Study is designed to evaluate the efficacy of the drug (whether early treatment with ISIS-SMNRx, before the signs of the disease are evident, could delay or prevent the development of the disease and its symptoms) and to further investigate the safety and tolerability of ISIS-SMNRx. This study initiated in February and one patient has been dosed at this time. The NURTURE Study will take place at clinical centers worldwide (US, EU, The Middle East, South America, and Asia Pacific). The EMBRACE Study is designed to evaluate the safety and exploratory efficacy of the drug in a small subset of patients with infantile or childhood-onset SMA who do not meet the age and other criteria of the ongoing Phase 3 studies ENDEAR & CHERISH. This study initiated in June and will take place at clinical centers in the US and EU. Biogen will post the location of each participating center (in each participating country/geography) on as soon as they are available.

RG7800 – Roche/PTC

Roche is developing investigational SMN2 splicing modifiers for spinal muscular atrophy in collaboration with PTC Therapeutics and the SMA Foundation called RG7800. Effects of SMN2 splicing modifiers in SMA animal models have been published (Naryshkin et al. 2014).

RG7800 is an oral SMN2 splicing modifier in early clinical development. A single dose study in healthy volunteers has been completed and a trial in SMA patients (Moonfish) started late 2014 and has dosed the first cohort. Currently, the trial is on clinical hold due to an unexpected finding in a long term monkey study.

LMI070 – Novartis

Novartis has started a new clinical study to evaluate LMI070, a novel investigational oral compound, for the potential treatment of infants with Type I spinal muscular atrophy (SMA). LMI070 treatment in animals prolonged survival and increased the amount of functional SMN protein due to more efficient splicing of the SMN2 gene. LMI070 is being tested to determine if can produce improved motor neuron survival, muscle growth, motor milestones, and respiratory function in infants with Type I SMA.

This First in Human study (NCT02268552) will evaluate the safety and tolerability of LMI070 in Type 1 SMA patients, and explore the potential therapeutic benefit in patients. This is an open label study; all patients will receive LMI070. Patients will receive LMI070 for 13 weeks. An increase in the dose of LMI070 and continuation of LMI070 treatment beyond the initial 13 weeks may be possible.To participate in the study, patients must be between 1-7 months of age when they enroll and must have two copies of the SMN2 gene.

This clinical study is open and recruiting in Europe and is posted on Clinical

Olesoxime – Roche

Roche finalized the acquisition of Trophos in March 2015, and will further develop olesoxime to bring it to people with spinal muscular atrophy.

Drug product needs to be manufactured and further development of the production and regulatory processes is needed. Further clarity on the submission timelines will come after meetings with health authorities later in 2015.

Roche considers patient organizations to be important partners. The company is committed to liaising with patient organizations and sharing information as it becomes available.