UK regulators grant innovation passport to AD04 for Alzheimer’s
Designation aims to speed development, approval of ADvantage therapy
An innovation passport, the first step in the U.K.’s Innovative Licensing and Access Pathway (ILAP) — intended to accelerate the development and approval of new therapies that address an unmet medical need — has been awarded to AD04, ADvantage Therapeutics’ investigational immunotherapy for mild Alzheimer’s disease.
The designation, granted by the Medicines and Healthcare products Regulatory Agency (MHRA), allows for significant input from patients at every development stage. It also offers collaborations with U.K. regulatory agencies, such as the National Institute for Health and Care Excellence (NICE), the Scottish Medicines Consortium (SMC), and NHS England and NHS Improvement (NHSE&I).
Meanwhile, the company is set to launch a proof of concept Phase 2b clinical trial to evaluate the safety and efficacy of AD04, administered by subcutaneous (under-the-skin) injection, in people with mild Alzheimer’s disease.
“We are delighted that MHRA has recognized the potential of AD04 at same time we are launching our confirmatory trial,” Jeffrey Madden, ADvantage’s CEO, said in a company press release.
“AD04 may completely change the approach to the treatment of Alzheimer’s disease,” Madden said, adding, “The ILAP designation creates an accelerated pathway to approval, commercialization, and patient access, by providing a more open dialogue with all the U.K. agencies, including NICE, which oversees access and integration of novel therapies into the National Health Service (NHS) and NHS Wales.”
AD04 showed promise in mouse studies of Alzheimer’s
Alzheimer’s is a progressive neurodegenerative disorder and the most common cause of dementia, a group of cognitive problems that include memory loss, confusion, and impaired reasoning. The disease is thought to be caused by the toxic buildup of misfolded proteins in brain nerve cells. Called amyloid plaques and tau tangles, these accumulated proteins damage nerve cells over time, leading to symptoms of the disease.
AD04 has been used in human and animal vaccination programs as an adjuvant — a substance that heightens the body’s immune response to vaccines, increasing their efficacy.
ADvantage believes the compound also addresses the immunological mechanisms that drive nerve cell damage in Alzheimer’s, including inflammation and the excess growth of brain immune cells, called microglial cells.
AD04 may completely change the approach to the treatment of Alzheimer’s disease.
In preclinical mouse studies, AD04 reduced the number of inflammatory microglial cells in the hippocampus — one of the brain areas affected by Alzheimer’s, with rapid tissue loss occurring in the early stages of the disease.
Serving as a control in a previous clinical study, 2 mg of AD04 significantly slowed the decline in cognition, function, and quality of life in people with early Alzheimer’s compared with other trial arms. The therapy candidate also slowed the loss of hippocampal volume, as assessed by MRI as a biomarker of disease progression.
According to the company, slowing hippocampal volume loss correlated with significantly less cognitive decline. The treatment was also found to be safe and well tolerated, with no signs of autoimmunity, blood abnormalities in the blood, liver or kidney toxicity.
“We believe our novel immunotherapy for Alzheimer’s has a low manufacturing cost, simple storage, subcutaneous administration, and believe that forthcoming clinical studies will confirm safety, efficacy and tolerability,” Madden said. “If proven and approved, the rapid introduction of AD04 into the U.K. health system may support accelerated clinical adoption in other worldwide healthcare systems.”
ADvantage aims to confirm AD04’s safety and efficacy in a Phase 2b trial, in which participants will be randomly assigned to receive the therapy or a placebo for one year. The study’s primary goal is to assess the therapy’s ability to slow hippocampal volume loss, but it also will assess its impact on measures of cognition, dementia, activities of daily living, and quality of life.
“The democratization of Alzheimer’s disease treatments that are safe, effective, and affordable for all are of utmost importance,” said Rudolph Tanzi, PhD, ADvantage’s scientific advisory board chair. “We hope this AD04 trial with ILAP designation will bring us one step closer.”