Early-stage clinical trial data for ISIS-SMNrx will be presented at the American Academy of Neurology (#AAN13) annual meeting on March 20, 2013. Continue reading below for the fulltext abstract of the data to be presented. Investors, patients, and the medical community will all be hoping for greater details at the actual platform presentation.
Oh, and don't forget that ISIS and Sanofi/Genzyme $SNY have an upcoming FDA PDUFA date for KYNAMRO (mipomersen) for homozygous familial hypercholesterolemia. Competitor Aegerion Pharma AEGR recently won FDA approval for JUXTAPID (lomitapide), but ISIS was rejected by the EU and faced greater criticism from a November FDA panel, leading to greater concern about mipomersen's prospects for approval.
Thanks to Jordan Bauman (@LifeSciGuy) for alerting me to the publication of the abstract.
[S36.002] Results of an Open-Label, Escalating Dose Study To Assess the Safety, Tolerability, and Dose Range Finding of a Single Intrathecal Dose of ISIS-SMNRx in Patients with Spinal Muscular Atrophy
Claudia Chiriboga, New York, NY, Kathryn Swoboda, Salt Lake City, UT, Basil Darras, Boston, MA, Susan Iannaccone, Dallas, TX, Jacqueline Montes, New York, NY, Heather Allen, Salt Lake City, UT, Rebecca Parad, Boston, MA, Shanda Johnson, Dallas, TX, Darryl De Vivo, New York, NY, Daniel Norris, Carlsbad, CA, Katie Alexander, Carlsbad, CA, Frank Bennett, Carlsbad, CA, Kathie Bishop, Carlsbad
OBJECTIVE: This first-in-human study was conducted to evaluate the safety, tolerability, and pharmacokinetics of escalating single intrathecal doses of ISIS-SMNRx (ISIS 396443) in patients with SMA.
BACKGROUND: ISIS-SMNRx is an antisense oligonucleotide (ASO) molecule designed to alter splicing of SMN2 mRNA to increase the amount of functional SMN protein produced. Results from experiments in SMA mouse models showed that ISIS-SMNRx effectively altered SMN2 mRNA spicing and increased SMN protein in the spinal cord and had a significant effect on functional and histological measures of neuromuscular health, including survival, when delivered to the CNS.
DESIGN/METHODS: A single dose of ISIS-SMNRx was delivered by intrathecal injection to medically stable SMA patients 2-14 years of age. Four escalating dose levels (1, 3, 6, 9 mg) were examined in cohorts of 6-10 subjects (n=28). Subjects were followed for 29 days (cohorts 1, 2) or 85 days (cohorts 3, 4) post-dosing and monitored for drug safety and tolerability. Plasma drug levels were measured over the first 24 hours and CSF drug levels were assessed at 7 days post-dose.
RESULTS: No serious adverse events or dose-limiting toxicities were reported. All adverse events were mild or moderate in severity and none were related to dose level of ISIS-SMNRx. No drug-related changes in neurological exams, laboratory assessments (including CSF safety and cytokines), or systemic evaluations were reported. Intrathecal injections were well tolerated in SMA children. Analysis of drug pharmacokinetics in plasma and CSF indicate that drug levels in SMA patients were dose-dependent and consistent with levels predicted from pre-clinical animal studies.
CONCLUSIONS: ISIS-SMNRx is well tolerated when given as a single dose at the dose levels evaluated in this study; no safety concerns have been identified. Results from this study support continued development and further examination of ISIS-SMNRx in a longer multiple-dose clinical study in SMA patients. Supported by: Isis Pharmaceuticals, Inc. Carlsbad, CA.
Category - Anterior Horn: Therapeutics
Wednesday, March 20, 2013 4:13 PM
Moderated Platform Session S36: Anterior Horn: Clinical Trials (4:00 PM-5:30 PM)