Spinal Cord Injuries

November 12, 2012

Chelsea Therapeutics International issued results from a phase III trial of Northera (droxidopa) for the treatment of spinal cord injury (SCI). This multi-arm, dose-escalation study enrolled hypotensive patients with spinal cord injuries. The level of SCI ranged from cervical to low thoracic lesions; all were chronically injured and non-ambulatory and eight were motor complete. Subjects received three doses of droxidopa 100mg, 200mg or 400mg. Results showed subjects were hypotensive at baseline (systolic BP: 87±14mmHg; diastolic BP: 54±8mmHg), and baseline BP did not differ among the three visits. Upon supine repositioning prior to drug administration, BP increased significantly (SBP: 101±11mmHg; DBP: 62±7mmHg; p<0.0001 versus seated baseline), regardless of dose, and droxidopa did not augment the increase in BP upon supine repositioning. Seated BP was significantly increased from baseline after droxidopa in a dose-dependent manner (100mg: 94±14/61±8mmHg; 200mg: 99±15/62±9mmHg; 400mg: 106±16/58±9mmHg; p<0.0001). Although the elevation in seated BP was relatively modest, average four-hour seated SBP & DBP were significantly increased with 400mg droxidopa compared to 100mg (p<0.001) and 200mg (p<0.05). The drug was well tolerated. Chelsea Therapeutics will continue to study droxidopa in the SCI population.

June 13, 2011

Geron issued interim results from a phase I trial of GRNOPC1, a human embryonic stem cell-based therapy for spinal cord injuries. Data are from two subjects with neurologically complete American Spinal Injury Association Impairment Scale grade A thoracic spinal cord injuries between spinal segments T3 and T10. The subjects received GRNOPC1 at a dose of 2 million cells delivered by injection into the lesion site, administered between seven and 14 days after injury. Low-dose tacrolimus was given for temporary immune-suppression from the time of injection through 60 days. There were no surgical complications during or after either procedure. There was no evidence of cavitation in the spinal cord at the injury site on MRI through Day 180. Initial analyses showed no evidence of immune responses to GRNOPC1 through Day 90, which includes 30 days after complete withdrawal of immune-suppression. No adverse events have occurred.

July 6, 2009

XenoPort reported positive results from a phase II trial of arbaclofen placarbil (XP19986) for the treatment spasticity due to spinal cord injury. This randomized, double-blind, placebo-controlled, crossover study enrolled 37 subjects with spinal cord injury between C-5 and T-12 in North America. The subjects discontinued spasticity therapy during a one-week washout period prior to a one-week placebo run-in period, at the end of which baseline assessments were conducted. They then received either arbaclofen placarbil (10, 20 or 30 mg) or placebo twice daily in the first treatment segment of the two-segment crossover design. After another washout period, the reverse treatment was administered in the second segment. The primary endpoint was the difference in Ashworth Scale score during the placebo and arbaclofen placarbil treatment segments for the muscle group with the highest Ashworth Scale score at baseline. Data are from 35 subjects who completed both treatment segments. Mean maximum baseline Ashworth Scale scores were 3.2, 3.1 and 3.1 for the 10, 20 and 30 mg dose cohorts, respectively. For the primary endpoint, the overall adjusted mean differences between placebo and arbaclofen placarbil over the six-hour assessment period for these cohorts were -0.17, -0.60 (p≡0.0059) and -0.88 (p≡0.0007), respectively. Arbaclofen placarbil treatment was associated with statistically significant differences from placebo at all time points in the 20 and 30 mg BID AP dose cohorts, indicating a treatment effect over the 12-hour dosing interval. In a secondary analysis, 20 and 30 mg of arbaclofen placarbil also showed a statistically significant difference from placebo in the average Ashworth Scale score for all six muscle groups. Treatment was well tolerated at all dose levels.

May 19, 2008

Alseres released positive interim results from a phase I/IIa trial of Cethrin for the treatment of neurological recovery following acute spinal cord injury. This open label study enrolled 48 subjects in the US and Canada with thoracic or cervical spinal cord injury. The subjects received escalating doses of Cethrin (0.3, 1, 3, 6 or 9 mg) administered to the injured spinal cord during spinal decompression surgery. Neurological outcomes were measured using the American Spinal Injury Association (ASIA) Impairment Scale at 0, 1.5, 3, 6 and 12 months after treatment. Data is from 37 subjects, all with cervical injuries, who received doses up to 6 mg and who had reached the final 12 month follow up evaluation. Data from six and twelve months showed 38% of the subjects demonstrated a 2-grade or better ASIA grade improvement. Subgroup analysis indicated a dose related response with 43% of the subjects from the 1 and 3 mg dose groups demonstrating improvement of at least 2 ASIA grades. Two of these three subjects improved 3 levels from ASIA grade A to ASIA grade D. Subgroup analysis of twelve month mean motor score changes showed improvement in both the 1 and 3 mg dosage groups with mean motor score changes of 16.3 points in the 1 mg and 27.3 points in the 3 mg doses. Hence, the most effective Cethrin doses for this population were determined to be 1 and 3 milligrams. Dosing in the 9 mg cervical and thoracic cohorts is currently underway. Based on positive data Alseres plans to commence a phase IIb trial in the second half of 2008.

December 4, 2006

Bioaxone Therapeutics issued positive interim results from a phase I/IIa trial of Cethrin for the treatment of acute spinal cord injury. This trial enrolled 37 subjects across the US and Canada who suffered a complete thoracic or cervical injury. Subjects received Cethrin at four dose levels (0.3, 1, 3 and 6 mg) and were to be followed for a year to assess safety, tolerability and neurological outcome profiles. Six month data has revealed treatment to be safe and well tolerated. In addition, 31% of the subjects had recovered some sensory and/or motor function below the level of their injury and converted from a complete injury to an incomplete injury. Bioaxone plans to move development of Cethrin into further development.