Hope on the horizon for Alzheimer's disease detection and treatment
Dear fellow ProMIS shareholders,
Two major recent developments in the Alzheimer's field are now offering real hope for patients and caregivers.
The first was Biogen's announcementon Aug. 7, 2020, that the US FDA accepted their BLA (biologic license application) and granted Priority Reviewstatus to aducanumab, an amyloid-targeting antibody therapeutic for treatment of Alzheimer's disease (AD). According to the FDA statutes, 'A Priority Review designation will direct overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.'
There is strong reason for optimism that 2021 will see the first new drug approval for AD in decades, and the first ever approval of a disease-modifying drug for AD. In three clinical trials over the last several years, aducanumab has shown modest but approvable clinical benefit, a reduction in disease progression of approximately 30%, but only at the highest dose of 10 mg/kg after prolonged administration. Approximately one third of patients treated with aducanumab also showed a dose-limiting toxicity of brain swelling or edema called ARIA-E (Amyloid Related Imaging Abnormality - Edema). Binding to - and disruption of - amyloid plaque is widely believed to be the cause of the edema associated with aducanumab therapy.
Priority Review status requires the FDA to make a decision within 6 months, which means a decision should be public in Q1 of 2021. If marketing approval is in fact the outcome (as we expect) , it will be a turning point in AD that will likely accelerate the demand for diagnostic testing and screening, and increase the amount of investment in second-generation therapies selectively targeting the toxic oligomers of amyloid beta (ABOs). Unlike aducanumab, an oligomer-selective antibody like ProMIS' lead therapeutic candidate PMN310 does not bind to or disrupt amyloid plaque, and is anticipated to provide improvement over aducanumab's modest clinical benefit and dose-limiting side effect profile.
The second breakthrough this year relates to major progress in the search for blood-based biomarkers (diagnostic assays) that can correlate very well with expensive imaging evaluations (MRI and PET scans) or assessments of spinal fluid from lumbar puncture. There is consensus in the Alzheimer's expert community that we have entered a new era. While more work and further development are required, we now know that it is possible to detect and monitor ongoing Alzheimer's neuropathology in blood. Two measures have been scientifically validated: neurofilament light chain (NfL), which measures the rate of neuronal loss, and phosphorylated tau (P-tau) which measures the level of toxic, mis-folded tau. Blood levels of these biomarkers have been shown to correlate with brain imaging measures and disease status or progression. These two biomarkers are almost certainly the first of a growing list of convenient blood-based biomarkers to detect and support monitoring of Alzheimer's disease. This major advance opens the door to early detection and prevention of Alzheimer's disease, just as measuring HbA1c in blood is critical for preventing the complications of diabetes and measuring lipid levels in blood is critical for preventing heart disease and stroke.
To pursue these diagnostic opportunities, ProMIS has entered into a joint venture agreement with BC Neuroimmunology (BCNI), an accredited diagnostic laboratory in Vancouver, BC. BCNI currently provides 23 diagnostic tests and serves as the North American reference standard for six of these. ProMIS and BCNI will first offer assays that are emerging standards (like NfL and P-tau for detection of ongoing AD pathology) and then subsequently offer assays based on ProMIS proprietary targets. This approach gives ProMIS the most rapid and controllable means to pursue near-term diagnostic revenue in the emerging field of early AD detection.
As the ability to achieve early detection of AD develops, in part due to ProMIS/BCNI diagnostic services and innovations, the need for preventive treatment will grow. Therapeutic vaccines can be used for that purpose. Using the ProMIS discovery platform, our aim is to devise a safe and effective vaccine to induce a specific immune response against toxic ABOs. For this purpose, we have identified a set of 6 unique peptide epitopes selectively exposed on toxic ABOs. A multivalent vaccine approach will be used in order to maximize potency by coupling most or all 6 peptides to a carrier protein to elicit a multi-pronged antibody response. ProMIS has published preliminary, positive scientific results creating an anti-amyloid oligomer Alzheimer's vaccine, and plans to expand that program and progress it to the clinic.
In summary, the ongoing FDA priority review and the anticipated approval of aducanumab in early 2021, the first ever disease-modifying therapy for AD, will stimulate significant progress in the AD field. A key outcome of this anticipated regulatory approval will be the development of second-generation, ABO-selective therapeutic antibody treatments (e.g., PMN310) that will offer greater efficacy and an improved safety profile compared to aducanumab. The further development of convenient and reliable blood-based biomarkers is anticipated to open up the field of early, pre-symptomatic detection and monitoring of Alzheimer's neuropathology, and spur the development of ABO-selective vaccines for prevention of disease progression.
There is clearly hope on the horizonfor the detection, treatment and ultimately the prevention of Alzheimer's disease!