HALLE/SAALE, Germany—April 4 saw Probiodrug AG, a biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer’s disease (AD), announce that it has finished assessing its chronic toxicology studies with regard to lead candidate PQ912, currently under development for AD in a clinical phase 2 study known as SAPHIR.
PQ912 is a highly specific and potent inhibitor of glutaminyl cyclase (QC), which has shown therapeutic benefit in Alzheimer’s animal models. PQ912 is the first QC inhibitor being tested in AD patients, putting Probiodrug in a position to have a first-in-class Alzheimer’s therapeutic if trials go well and lead to approvals.
In 2015, Probiodrug began its Phase 2a study, SAPHIR, after a preceding Phase 1 study with healthy young and elderly volunteers indicated that PQ912 seemed to be safe and well tolerated, as well as revealing its high QC inhibition properties.
In addition, other research results show that the toxicology profile of PQ912 in the six-month rat and nine-month dog studies was absolutely comparable to the results of the previously available three-month toxicology studies conducted in the same species. No new findings were observed and, according to the company, “the minimal to slight non-adverse or questionable changes seen in both the one-month and the three-month studies were not aggravated after prolonged treatment, thus providing an excellent basis for a sound preclinical safety assessment. In conclusion, the comfortable safety margin is retained.”
Based these outcomes, Probiodrug is exploring opportunities for longer-term clinical studies in AD, which may be run either as separate trials or as an extension of the SAPHIR trial.
“We are very pleased with the conclusions from these peer-reviewed results of the long-term toxicology studies as we view them as the regulatory prerequisite for longer treatment clinical studies in AD patients,” said Inge Lues, chief development officer of Probiodrug.
The Phase 2a study is a randomized, double-blind multicenter study which plans to enroll a total of 110 patients with early-stage Alzheimer’s disease in six European countries at about 18 sites. The primary endpoint of the trial is the safety and tolerability of PQ912 compared with placebo over a three-month treatment period. Additionally, a set of exploratory readouts comprising cognitive tests, functional assessments by EEG and functional MRI and new molecular biomarkers in CSF will be used to evaluate the compound’s effect on the pathology of the disease. Patient enrolment started in March 2015.
Across the Atlantic Ocean, in other Alzheimers’ disease Phase 2a news (albeit nearly a month older), New York City-based Anavex Life Sciences Corp. announced that it had received approval by the ethics committee in Australia to extend an ongoing Phase 2a trial, which had been requested by patients and their caregivers. The trial extension is designed to allow participants who complete 52 weeks in PART B to rollover into a new trial and continue taking ANAVEX 2-73 for an additional 104 weeks, providing an opportunity to gather extended safety and efficacy data. The study is independent of the company’s planned larger Phase 2/3 double-blinded, placebo controlled study of ANAVEX 2-73 in Alzheimer’s disease.
“We are receiving continued positive feedback about the effects of ANAVEX 2-73 from our study participants and their caregivers,” said Stephen Macfarlane, the principal investigator of the study. “In addition to the measured cognitive and functional benefits witnessed so far, an overall improvement in mood and decrease in agitation has been anecdotally reported. We believe that extending the study will lead us to an increased understanding of the long-term effects of ANAVEX 2-73.”
“Safety is a key requirement for potential drug approval and we believe the approval to further extend this study, which is already in its second extension period, is an important step forward for patients, caregivers and physicians, who have asked for continued access to ANAVEX 2-73,” said Dr. Christopher U. Missling, president and CEO of Anavex. “While we are waiting for longitudinal effect data of ANAVEX 2-73 over an extended period of time, the positive dose-response in PART A is an encouraging step and also consistent with the fast mode of action of the sigma-1 receptor activation.“
