|Paclitaxel Shows Benefits in Secondary MS
ANA: Paclitaxel Shows Benefits In Secondary Progressive MS
VANCOUVER, B.C. -- October 15, 1999 -- Patients with secondary progressive multiple sclerosis (SPMS) treated with monthly intravenous infusions of Angiotechs micellar paclitaxel showed favourable trends in Expanded Disability Status Scale (EDSS) score, MS functional scores, quality of life and magnetic resonance imaging (MRI) burden of disease.
Dr. Paul OConnor, of St. Michaels Hospital, in Toronto, ON, presented these findings of a phase I/II study were reported earlier this week at the American Neurological Associations (ANA) 124th Annual Meeting in Seattle, WA.
A total of 29 patients with EDSS scores ranging between 3.5 (some neurological disability) and 6.5 (unable to walk without a walker or two canes) were treated monthly with 25 or 50 mg/m2 of intravenous micellar paclitaxel for a total of six months.
No drug-related serious adverse reactions were observed. When compared to baseline, favourable trends were observed in EDSS change (improvements of 0.35 for the low-dose group and 0.27 for the high-dose group) and in the proportion of patients showing stabilization or improvement of their condition (80 percent and 85 percent respectively).
When the study results were compared to a historical placebo group (63 SPMS placebo-treated subjects from the North American Linomide Trial which closely matched the two micellar paclitaxel-treatment groups for clinical and MRI parameters at baseline), the change in EDSS from baseline statistically favoured the micellar paclitaxel-treated patients (i.e., placebo-treated patients worsened by 0.27, while micellar paclitaxel-treated patients improved by 0.27 to 0.35).
In functional testing, a statistically significant proportion of patients in both dosing groups (p=0.02 and 0.03, low and high dose respectively) showed improvement in the 9-hole peg test (the time it takes to put 9 pegs into a pegboard). In the Paced Auditory Serial Addition Test (the time taken to add up a series of numbers), again it was found that in both micellar paclitaxel groups a statistically significant proportion of patients improved compared to baseline (p=0.02 and 0.001, low and high dose respectively). For the timed 25-foot walk, only the high dose group demonstrated a statistically significant improvement over the six month investigation (p=0.27 and p=0.03, low and high dose respectively).
Patients were also evaluated by MRI (computer-assisted analysis of AFFIRMATIVE and T1 images) before the initiation of, and after the completion of, treatment. Positive trends were seen for changes in the MRI burden of disease that favoured the patients treated with 50 mg/m2 micellar paclitaxel. The median percent increase in burden of disease was as follows: 6.7 percent for historical controls, 6.23 percent for low dose, and 1.2 percent for high dose; suggesting that micellar paclitaxel treatment slowed disease progression in the higher dose range. In conclusion, micellar paclitaxel treatment was very well-tolerated and demonstrated favourable improvement trends in both clinical and MRI parameters of SPMS.
Based on these impressive results (and at the patients and investigators requests), Angiotech has continued to treat a majority of these patients for ethical and compassionate purposes for an additional six months.
Later this year, Angiotech plans to initiate a 190-patient, double-blinded, placebo-controlled, phase II MS study at multiple centers across Canada.
Multiple sclerosis is a chronic inflammatory and progressive disease, with debilitating neurological symptoms occurring over a period of several years. Although the disease does not result in early death, it disables patients by disturbing vision, strength, balance and sensation, as well as causing fatigue and cognitive problems. Secondary progressive MS is comprised of 40 percent of all MS patients. It is the most severe form of MS, which follows the relapsing-remitting phase of the disease.
The estimated 1999 U.S. treatment market for MS is US$891 million.