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Isis Pharmaceuticals Reports Interim Results from ISIS-SMN Rx Multiple Dose Study in Children with Spinal Muscular Atrophy
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"We continue to be encouraged with the tolerability of ISIS-SMNRx we have observed in our clinical studies to date. We are also encouraged that we observed dose- and time-dependent increases in muscle function scores in children with SMA. The consistency of the results between the single-dose and the multiple-dose studies supports our earlier optimism around the single dose study results and gives us further confidence to advance ISIS-SMNRx into a Phase 3 program in children with SMA, which we plan to start later this year," said
In the interim analysis of this ongoing multiple-dose Phase 1b/2a study, children with Type II or Type III SMA were dosed intrathecally with 3 mg, 6 mg or 9 mg of ISIS-SMNRx. The 3 mg and 6 mg doses were administered on days 1, 29 and 85. The 9 mg dose was administered on days 1 and 85. Muscle function changes were measured using the Hammersmith Functional Motor Scale-Expanded (HFMSE), a validated method to measure changes in muscle function in patients with SMA. Using this test, dose-dependent increases in muscle function scores were observed in this study. SMA children in the 3 mg, 6 mg and 9 mg cohorts achieved mean increases in HFMSE scores of 1.5, 2.3 and 3.7 points, respectively, nine months following the first dose of ISIS-SMNRx. In addition, time-dependent increases in muscle function scores were observed. Children in the 9 mg cohort achieved mean increases in HFMSE scores of 2.7 and 3.7 points three and nine months after the first dose of ISIS-SMNRx, respectively. The increases in muscle function scores observed in this study at the three month time point is comparable to the single-dose data presented last year, which showed that children treated with 9 mg of ISIS-SMNRx achieved a mean increase in HFMSE score of 3.1 three months after the single-dose. All children in the multiple-dose study have completed dosing in the initial three cohorts and the first child has been dosed in the 12 mg cohort. Isis' plans to give all children who roll over into an extension study a maintenance dose of 12 mg of ISIS-SMNRx every six months. To date, ISIS-SMNRx has been well tolerated. Two serious adverse events (pneumonia and fentanyl-related hypersensitivity) that were not considered drug related were reported.
"A subgroup analysis that combines data from children in both the single- and multiple-dose studies demonstrated a mean 5 point increase in muscle function score in children who received at least 9 mg of ISIS-SMNRx between the ages of two and 10 who did not have severe scoliosis or baseline HFMSE scores at the extreme low or high ends of the scale. These results provide us with valuable insight into determining which children with SMA can achieve increases in Hammersmith scores that best correlate with increases in muscle function," said
In addition, analysis of CSF samples from both the single dose and the ongoing multiple dose studies demonstrated dose-dependent increases in SMN protein levels over time in patients treated with ISIS-SMNRx. In the single dose study, SMN protein levels more than doubled in the two highest dose cohorts with average increases of approximately 120% and 160% compared to baseline observed approximately 9-14 months after dosing in the 6 mg and 9 mg cohorts, respectively. Similarly, in the multiple dose study, patients in the 9 mg cohort all exhibited a substantial increase in SMN protein levels. At Day 86, SMN protein levels more than doubled with an average increase of 115% compared to baseline.
Isis plans to report additional detail from this study at an upcoming medical conference. For further study information, please visit www.clinicaltrials.gov and search for ISIS-SMNRx or by the identifier number, NCT01703988.
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ISIS-SMNRx is also being evaluated in an open-label, multiple-dose, dose-escalation Phase 2 study in infants with Type I SMA. In the ongoing Phase 2 study, doses of either 6 mg or 12 mg are administered intrathecally on Days 1, 15 and 85. 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. Isis announced late in 2013 that the study was expanded to enroll up to 20 infants and that the first infant was dosed in the 12 mg dose cohort. Infants from the 12 mg dose cohort will also be eligible to receive an additional 12 mg dose six months after they have completed the initial three scheduled doses. Infants may enroll in the Phase 2 study if they are between the ages of three weeks and seven months, live in close proximity to a study site and pass screening evaluations conducted at study sites. The study is being conducted at centers in
ABOUT ISIS-SMNRx
ISIS-SMNRx is designed to alter the splicing of a closely related gene (SMN2) to increase production of fully functional SMN protein. The United States Food and Drug Administration granted orphan drug status and fast track designation to ISIS-SMNRx for the treatment of patients with SMA. Isis is currently in collaboration with
Isis acknowledges support from the following organizations for ISIS-SMNRx:
ABOUT SMA
SMA is a severe genetic disease that affects approximately 30,000-35,000 patients in
ABOUT ISIS and
ABOUT
Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners. Isis' broad pipeline consists of 31 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic, severe and rare diseases, including neurological disorders and cancer. Isis' partner, Genzyme, is commercializing Isis' lead product, KYNAMRO®, in
This press release includes forward-looking statements regarding Isis' alliance with
In this press release, unless the context requires otherwise, "Isis," "Company," "we," "our," and "us" refers to
Isis Pharmaceuticals® is a registered trademark of
SOURCE
D. Wade Walke, Ph.D., Vice President, Corporate Communications and Investor Relations, 760-603-2741; Amy Blackley, Ph.D., Associate Director, Corporate Communications, 760-603-2772