Today, Isis released results from their Phase II open-label clinical trials of ISIS-SMNRx. These results covered two separate trials: a trial in infants with SMA type I, and a trial in children with SMA type II.

Isis previously announced recruitment for a Phase III trial of infants with SMA type I. This is the first-ever Phase III trial for a drug that may treat the underlying cause of SMA. Recruitment for a Phase III study in children will begin later this year.

Cure SMA was one of the earliest funders of this therapeutic approach. Our funding lead to intellectual property, which U Massachusetts licensed to Isis to help create ISIS-SMNRx.

We are excited to see this drug move one step closer to possible FDA approval. We know that the path to a treatment and cure for spinal muscular atrophy will require continued, aggressive investment in this and other promising therapeutic approaches.

We recently committed $1.8 million to new research funding, and we expect that $1 million of that will be announced over the next few months.

More on the Results

Read the complete announcement from Isis.

Type I Trial Data

In the Phase 2 study in infants with SMA, a total of 20 infants were dosed as of Sept 1st, four infants in the 6 mg cohort and 16 infants in the 12 mg cohort. As of September 2, 2014, the date for this data update, the PPEP (patients who completed the three dose induction regimen in the study) constituted four patients in the 6 mg and 12 patients in the 12 mg dose cohorts.

In the 6 mg cohort, as of September 2, 2014, there have been two events (one accidental death and one permanent ventilation) in the 6 mg cohort. Isis previously reported a median event-free age of 14 months for the infants in the PPEP on April 7, 2014. The median event-free age on September 2, 2014 for the infants in this group is now 16.3 months.

In the 12 mg cohort, dosing began five months after the initiation of dosing for the 6 mg cohort. As a result, the patients in the 12 mg cohort have participated in the study for a shorter time than those in the 6 mg cohort. As of September 2, the PPEP for the 12 mg dose cohort contained 12 infants, which included an additional five infants who had more recently entered the study. The median event-free age of the 12 infants in the PPEP as of September 2, 2014 for the 12 mg cohort is 11.6 months. Of these 12 infants, nine are alive without the need for permanent ventilation. As of September 2, 2014, there have been four events (one permanent ventilation and three deaths, all related to respiratory infections) in the 16 infants from the 12 mg cohort.

Increases in muscle function scores are also observed in the study in infants with SMA Increases in CHOP INTEND scores occurred in a majority of infants in the study. Infants in the PPEP from the 6 mg and 12 mg cohorts combined showed mean increases from baseline in CHOP INTEND of 9.3 points with 14 of the 16 infants showing an increase in CHOP INTEND scores.

Today, Isis also reported the results from an analysis of spinal cord tissue samples from autopsies showing that ISIS-SMNRx is distributed throughout the central nervous system. Greater level of full-length (containing exon 7) SMN2 mRNA was observed in the spinal cord and brain tissue of ISIS-SMNRx-treated SMA infants compared to the level of full-length SMN2 mRNA in the untreated SMA infants. In patients treated with ISIS-SMNRx, greater amounts of SMN protein were observed in the spinal cord compared to the amount of SMN protein observed in the untreated SMA infants.

Type II Trial Data

In the ongoing, open-label study in children with SMA, increases in muscle function scores, as measured by the Hammersmith Functional Motor Scale-Expanded (HFMSE), were observed in children treated with multiple-doses of ISIS-SMNRx. As previously reported in April 2014, children in the 3 mg, 6 mg and 9 mg cohorts achieved mean increases from baseline of 1.5, 2.3 and 3.7 points, respectively, 9 months following their first dose (six months after last dose). Further evaluation of these children showed that the previously observed mean increases in muscle function scores continued to show increases from baseline for an extended period after their last dose with mean increases from baseline of 1.7, 3.2 and 2.3, respectively, eight to 13 months after last dose.

Increases in two additional functional tests were also observed eight to 13 months after last dose in the six-minute walk test (6MWT) and the upper limb mobility (ULM) test. In the 6MWT, performed with 10 ambulatory children, a mean increase of 24.4 meters was observed 12 to 16 months after the patients’ baseline visits, compared to the previously reported increase of 22.7 meters at nine months. In the ULM test, a mean increase of 3.1 points was observed 11 to 16 months after the patients’ baseline visits, compared to the previously reported increase of 2.3 points at nine months.

The safety and tolerability profile of ISIS-SMNRx continues to support continued development. As of September 2, 2014, 56 children have been exposed to doses ranging from 1 mg to 12 mg of ISIS-SMNRx. The majority of these children have received multiple doses of drug and in total 183 doses of ISIS-SMNRx have been administered. The lumbar puncture procedure in SMA children has been well tolerated and shown to be feasible. In all children dosed, there have been no drug-related serious adverse events. Most of the adverse events (non-SAEs) have been mild or moderate in severity and not related to drug. There were no changes in the safety profile with repeated doses of ISIS-SMNRx.