Trial Results

Alnylam Achieves Alignment with FDA on Accelerated Development Path for Lumasiran

May 14, 2018

Alnylam Pharmaceuticals announced that the company has reached alignment with the U.S. Food and Drug Administration (FDA) on a pivotal study design for lumasiran, an investigational RNAi therapeutic for the treatment of primary hyperoxaluria type 1 (PH1). The company and the FDA have aligned on a primary endpoint for the pivotal study based on reduction of urinary oxalate at six months, a biomarker directly linked to the pathophysiology of PH1 and known to be well correlated with disease progression. In addition, Alnylam and the FDA have aligned on a study size of approximately 25 patients with PH1. The ongoing Phase I/II Part B study is designed as a randomized, single-blind, placebo-controlled trial. Lumasiran demonstrated a mean maximal reduction in urinary oxalate of 66 percent with monthly dosing at 1 mg/kg in the unblinded Cohort 1 of the study (N=4), with all patients achieving urinary oxalate levels at or near the normal range. Moreover, lumasiran lowered urinary oxalate excretion in all patients below a threshold well documented to be associated with reduced progression to end-stage renal disease. In all patients, lumasiran was generally well tolerated and the only drug-related adverse event (AE) reported was a mild and transient injection site reaction.

Bonti Announces Start of Phase II Trial For Muscle Pain
Bonti announced it has initiated dosing in its LANTERN-2 clinical trial, a Phase II clinical trial under Bonti’s LANTERN (Long-Acting NeuroToxin-E Relief, Non-opioid) clinical program aimed at treating focal muscle pain and reducing use of rescue medications, including opioids. LANTERN-2 is a randomized, placebo-controlled, ascending dose, double-blind clinical trial to evaluate the safety and efficacy of intramuscular (IM) injections of Bonti’s therapeutic product candidate, EB-001T, in subjects undergoing elective abdominoplasty (tummy tuck) surgery. The primary endpoint in this trial will be reduction of post-operative pain at rest as measured by the Numeric Pain Rating Scale (NPRS) over the first 96 hours. Secondary endpoints include NPRS during activity and patient use of rescue medications, including opioids, to address unrelieved pain. LANTERN-2 trial was based on favorable safety results from the recently completed LANTERN-1 clinical trial, which was Bonti’s first trial in the LANTERN program. EB-001T showed favorable safety in a wide dose range and was well tolerated, and in which the maximum tolerated dose was not reached.

Nektar Therapeutics Announces Initiation of a Phase Ib Clinical Study
Nektar Therapeutics announced that it has commenced dosing patients with systemic lupus erythematosus (SLE) in a Phase Ib clinical study evaluating NKTR-358, a first-in-class regulatory T cell stimulator. NKTR-358 selectively stimulates the proliferation and activation of regulatory T cells (Tregs) in the body in order to restore the body’s self-tolerance mechanisms. The Phase Ib study is a double-blind, randomized, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics and immunological effects of multiple ascending doses of NKTR-358 in approximately 50 patients with systemic lupus erythematosus (SLE). The study will also evaluate the effects of NKTR-358 on disease activity in SLE patients. In preclinical studies, NKTR-358 has demonstrated that it could suppress antigen-driven inflammation in a model of cutaneous hypersensitivity. NKTR-358 has also shown that it reduces markers of progression in a mouse model of SLE. NKTR-358 is being developed as a once- or twice-monthly self-administered injection for a number of auto-immune diseases.

vTv Announces Post- hoc Analysis for Experimental Alzheimer’s Drug
vTv Therapeutics announced that based on post-hoc analyses of the data from Part A of the Company’s Phase II STEADFAST study of the investigational medication azeliragon in people with mild Alzheimer’s disease, despite not meeting co-primary endpoints, identified a subpopulation that showed statistically significant benefit (unadjusted for multiple, post hoc comparisons) from azeliragon relative to placebo on ADAS-cog. The patients in the identified subgroup (n=~48) had a -1.9 point improvement in ADAS-cog relative to the placebo group (n=200) which was statistically significant (unadjusted for multiple, post hoc comparisons) (p = 0.02), and a 0.5 point improvement on CDR-sb relative to placebo (p = .06) despite the smaller sample size. This benefit was observed at 12 months. These findings are consistent with results from an earlier Phase IIb study of azeliragon, in which there was a dose response with improved results in patients who had lower concentrations of azeliragon. In contrast, participants in the Phase IIb and STEADFAST Part A study with high azeliragon concentrations performed worse on the ADAS-cog relative to placebo. The STEADFAST study, two independent and identical randomized, double-blind, placebo-controlled Phase III trials (Part A and Part B), was designed to investigate the safety and efficacy of azeliragon as a potential treatment for patients with mild Alzheimer’s disease. The 18-month study targeted enrollment of 800 patients (400 in each trial). Over the course of 18 months, patients with mild Alzheimer’s registered a 4.0 point improvement on the using the ADAS-Cog11 assessment scores. The first trial enrolled patients in the U.S. and Canada.