Cure SMA Releases 2016 Updates from Drug Programs in Clinical Trials

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

Of these six programs, four— AVXS-101 (gene therapy), nusinersen, RG7800/RG7916, and LMI070—treat the underlying genetics of SMA. Gene therapy aims to replace the mutated 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 either the nerves or muscles, respectively.

For More Information

For more information on the importance of clinical trials and the regulatory process, you can download additional presentations from the Annual SMA Conference.

For more on the different phases, placebos, and other information on the clinical trial process, check out our SMA clinical trials care series booklet.

You can also download the slides presented at this panel.

Program Updates

Olesoxime – Roche/Genentech

Roche and Genentech are committed to addressing the urgent and unmet needs of the SMA community for an approved therapy. We are working to bring treatment options to people and families affected by the disease as soon as possible. We are currently evaluating the clinical development of two investigational medicines with different approaches in SMA – olesoxime and an SMN2 splicing modifier.

Since March 2015, Roche has been assessing and advancing the clinical development and manufacturing of olesoxime to meet health authority requirements and to hopefully gain market authorization to provide olesoxime to patients with SMA.

Roche has also consulted the US and EU health authorities on the adequacy of the clinical evidence currently available for olesoxime to establish the benefit/risk profile of this investigational medicine for the treatment of SMA. As a result, Roche will be conducting a Phase 3 study of olesoxime in people with Type 2/3 SMA. We will start the study as soon as possible.

People and families affected by SMA remain important partners to Roche and Genentech; we will continue to provide timely and relevant updates.

LMI070 – Novartis

Summary and Conclusions:

  1. 13 patients treated with LMI070; longest to date is ~14 months
  2. No Maximum Tolerated Dose (MTD) has been reached; Adverse Events (AE) have generally been mild and LMI070 has been well tolerated
  3. New target organs identified only in a chronic dog toxicology study
  4. Patients remain on study with dose modification and additional safety measures
  5. Excluding 2 pulmonary deaths, no patients have withdrawn from treatment
  6. Increases in CHOP INTEND and maintenance of independent feeding/ventilation are seen
  7. Recruitment temporarily paused
  8. Novartis is continuing the study of LMI070 as a treatment in Type 1 SMA

We have made the difficult decision to pause enrollment for our study of LMI070 for the treatment of Type 1 Spinal Muscular Atrophy (SMA). Animal safety studies were taking place in parallel with this trial, which is a common practice when studying potentially life threatening diseases to help bring medicines to patients faster. Results from an animal study, using daily dosing for a year compared to weekly dosing in the human study, showed unexpected injuries to the peripheral nerves and spinal cord, testes, and blood vessels in the kidney.

Patient safety is paramount to us and after a review of these results and in consultation with our Data Monitoring Committee, a team of independent experts who monitor the trial’s safety results, we decided to continue the trial but pause additional enrollment while we do further analysis.

All patients currently enrolled in the trial are being closely monitored and the teams at the clinical trial sites are working with their families to explain the findings, answer their questions, and help them decide whether they would like to continue. We are also working closely with our teams and health authorities to determine appropriate next steps.

Nusinersen – Biogen/Ionis

Biogen and Ionis Pharmaceuticals are working to develop the investigational compound, nusinersen, for the potential treatment of Spinal Muscular Atrophy (SMA). Currently, two Phase 3 registrational studies, ENDEAR and CHERISH are underway to provide the clinical data to support regulatory review and potential marketing approval if the studies are successful. ENDEAR is studying nusinersen in infants less than 7 months of age and CHERISH is studying nusinersen in children between the ages of 2-12.

Two additional Phase 2 studies, NURTURE & EMBRACE are also ongoing in order to collect additional data on nusinersen. The NURTURE study is studying nusinersen in pre-symptomatic infants to determine if treatment before symptoms begin would prevent or delay onset. The EMBRACE study is designed to collect additional data on a small subset of patients with infantile or childhood-onset SMA who do not meet the age and other criteria of ENDEAR & CHERISH. All studies are being conducted on a global scale. The NURTURE study is active and recruiting and the ENDEAR, CHERISH and EMBRACE clinical studies are all fully enrolled.

RG7800 & RG7916 – Roche/PTC/SMA Foundation

Roche, PTC Therapeutics and the SMA Foundation are collaborating to develop SMN2 splicing modifiers, RG7916 and RG7800, for people with SMA. RG7916 and RG7800 are investigational oral medicines, currently being explored for their ability to selectively modify splicing of SMN2 pre-mRNA, thus potentially producing more correct full-length SMN2 mRNA.

In April 2015, the MOONFISH clinical study, investigating the SMN2 splicing modifier RG7800 in people with SMA was placed on clinical hold. This was a precautionary measure after an unexpected finding was identified in an animal study exploring long-term treatment with RG7800 at concentrations above those in the MOONFISH study. Further development of RG7800 remains on hold. Patients who participated in the MOONFISH study may be potentially eligible to join an open-label safety study for RG7916. In December 2015, a clinical study in healthy individuals with a second SMN2 splicing modifier, RG7916, was started. Based on the results of this study, RG7916 is now advancing in development to clinical studies in people with SMA. Studies in people with Type 1 and Types 2/3 SMA are expected to start by the end of 2016.

CK-2127107 – Cytokinetics/Astellas

Cytokinetics, Inc. in collaboration with Astellas, is sponsoring a study of CK-2127107, an investigational drug, in patients with spinal muscular atrophy (SMA). CK-2127107 is a novel fast skeletal muscle troponin activator that may potentially improve muscle function. This Phase 2, double blind, randomized, placebo controlled trial is currently enrolling patients at sites throughout the US. Two sequential, ascending dose cohorts are planned. Patients must have genetically confirmed Types II, III or IV SMA, and be 12 years of age or older. Enrollment is estimated to be 72 individuals, divided between ambulatory and non-ambulatory status. The study will assess the effect of 8 weeks of dosing of CK-2127107 on measures of muscle function. Details on the study, including inclusion/exclusion criteria and trial sites, can be found online at; Identifier is NCT02644668.

AVXS-101 (Gene Therapy) – AveXis

  • In December of 2015, completed enrollment of 15 SMA Type I patients in ongoing Phase 1 Trial via intravenous (IV) delivery.
  • Pivotal trials of intravenous administration of AVXS-101 in SMA Type 1 are planned for 2017 in the U.S. and EU.
  • Study of intrathecal administration of AVXS-101 in SMA Type 2 patients is planned for the second half 2016.

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