Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

October 2, 2017

Alnylam Pharmaceuticals announced results of the APOLLO phase III study of patisiran for patients with hereditary ATTR amyloidosis with polyneuropathy. The APOLLO study is a randomized, double blind, placebo-controlled, global study. The primary efficacy endpoint was change from baseline in the modified neuropathy impairment score (mNIS+7) composite neuropathy impairment score at 18 months. The APOLLO trial enrolled 225 patients randomized 2:1 to patisiran or placebo, with patisiran administered intravenously at 0.3mg/kg once every three weeks for 18 months. For both the mNIS+7 and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) endpoint measures, a lower score indicates a better clinical result. At 18 months, the mean change from baseline in mNIS+7 was significantly lower in the patisiran group as compared with placebo (p<0.00001). The mean and median changes in mNIS+7 impairment scores for patisiran both achieved negative values, indicating an improvement overall and in the majority of patients compared with baseline. Patients in the patisiran group experienced improvement in quality of life compared to placebo (p<0.00001). Alnylam expects to file its first New Drug Application in late 2017 and first Marketing Authorization Application shortly thereafter. Sanofi Genzyme is currently preparing for regulatory filings for patisiran in Japan, Brazil and other countries, to begin in the first half of 2018.

June 26, 2017

Xencor reported results of a phase II trial of XmAb5871 in patients with active IgG4- related disease (IgG4-RD). As of a data cutoff, all 15 planned patients with active IgG4-RD have been enrolled and dosed with XmAb5871 (median number of infusions=12, range five to 12). Patients had a median IgG4-RD RI of 12 (range two to 30) with a median of five organs involved (range one to 10) at the time of study entry. Fourteen of the 15 patients (93%) dosed with XmAb5871 have had a response to XmAb5871 therapy of greater than or equal to a two-point reduction in the IgG4-RD RI (protocol defined response), 12 of them within two weeks of the first dose. At two weeks following the last dose, five patients had an IgG4-RD RI of zero and were on no corticosteroid therapy between months two to six (protocol definition of remission). In addition, a sixth patient achieved remission in the post-therapy follow-up period. All five of the patients that either entered the study on corticosteroids or that were administered corticosteroids at the beginning of the study have been able to taper and discontinue corticosteroids within two months of the start of the study. Organ site involvement occurring at a frequency of greater than or equal to 45% included lymph nodes, submandibular glands, parotid glands and lacrimal glands. In addition, 40% of patients suffered from constitutional symptoms at time of study entry. Every other week intravenous administration of XmAb5871 has been well-tolerated. Adverse events (AEs) were consistent with that previously reported, with all XmAb5871-related AEs graded as mild or moderate and no AE reported in more than two patients. No severe AEs deemed related to XmAb5871 were reported. One patient discontinued the study as the result of an AE of a moderate hypersensitivity reaction.

May 22, 2017

Ionis Pharmaceuticals reported results of the phase III NEURO-TTR study of inotersen (IONIS-TTRRx) in patients with familial amyloid polyneuropathy (FAP). Inotersen was evaluated in a randomized (2:1), double-blind, placebo-controlled, international study in 172 patients with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN). The study was designed to support an application for marketing approval of inotersen in patients with hATTR-PN. The 15-month study measured the effects of inotersen on neurological dysfunction and on quality of life by measuring the change from baseline in the modified Neuropathy Impairment Score +7 (mNIS+7) and in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) total score. Over the 15-month period of the study, inotersen-treated patients achieved statistically significant benefit compared to placebo in mNIS+7 and Norfolk QoL-DN (p<0.0001 and p=0.0006, respectively). Statistically significant differences were also observed for both endpoints at eight months. Treatment-emergent adverse events considered related to treatment were seen more commonly with inotersen than placebo. Two key safety findings were observed during the study that required changes to the monitoring schedule. Three serious adverse events of thrombocytopenia were observed in inotersen-treated patients; two patients recovered and one patient died due to intracranial hemorrhage. The preparation of regulatory marketing applications for inotersen is underway. GSK has the option to license inotersen following review of additional data and prior to the submission of regulatory applications.

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