FDA Approval of New Drug for Alzheimer’s Disease Underscores Need for DISCERN™ Accurate Diagnostic Testing Prior to Prescribing LEQEMBI™ and Finalizing Coverage

FDA approval of LEQEMBI™ (lecanemab) as a new drug for Alzheimer’s Disease (AD) is a great first step forward for making disease modifying therapies (DMT) available to patients and families in their fight against this debilitating condition that impacts millions of Americans.  

Importantly, this positive news marks a turning point for clinicians, payers and all stakeholders in the benefits community to add the DISCERN™ test to their armory of diagnostic weapons for preparing the health system for the introduction of this new drug.  

DISCERN Answers the Demands of Every Stakeholder for an Early, Accurate Diagnosis

“LEQEMBI is an amyloid beta-directed antibody indicated for the treatment of AD.”  Accurate diagnostic testing with DISCERN, developed by SYNAPS Dx, can efficiently inform a primary care provider if the patient recently diagnosed with dementia has AD, an important first step in understanding if the patient may be an appropriate candidate for treatment with LEQEMBI.  

Since the mechanism of action for LEQEMBI is to clear amyloid beta, the confirmation of the presence of amyloid is critical as a second step in people diagnosed with AD.

Value of DISCERN in Prescribing LEQEMBI: Starting with An Accurate Diagnosis

Unlike other diagnostic tests for AD, DISCERN is autopsy validated to identify AD in people recently diagnosed with dementia. No other diagnostic tests have undergone this rigorous autopsy validation for early dementia and no autopsy validated tests are available to accurately diagnose mild cognitive impairment (MCI) due to AD.

Once a patient is identified as having AD, the Alzheimer’s Association recommends blood tests and the availability of confirmatory diagnostic tools in specialty memory clinics to determine the presence or absence of amyloid plaques in the brain, a hallmark sign of AD and the target of treatment with LEQEMBI. 

DISCERN is designed to inform the presence of AD in people recently diagnosed with dementia, even when they have mixed-dementia. The DISCERN test assesses the factors directly related to the formation of synaptic connections in the brain impacting loss of memory and cognition in people living with AD as well as regulators of amyloid plaque and tau formation, hallmarks of AD at autopsy.

Validated in Clinical Trials

In clinical trials, DISCERN demonstrated >95% sensitivity and specificity for identifying AD versus the NIH Gold Standard definition for AD – dementia in life and the presence of plaque/tau upon autopsy. 

DISCERN was developed by following patients from initial diagnosis of dementia through death – on average eight years, at which point an autopsy was performed with the pathologists blinded to the initial diagnosis, and the results of assays were compared to the NIH standard.   

Unlike clinical AD diagnosis at the point of the initial diagnosis of dementia, DISCERN was highly accurate – >95% specificity and sensitivity versus 52% for clinical diagnosis.  

Codes and Reimbursement

DISCERN is currently commercialized under a CLIA authorization in 49 of 50 states (excluding NY), has received reimbursement codes and is currently paid for by Medicare Fee-For-Service.  Reimbursement is underway with commercial and Medicare Advantage payers.  

What Payers Need to Know about DISCERN

As the nation’s payers wrestle with coverage decisions regarding LEQEMBI, which is administered through an hourlong infusion every two weeks, on top of an acquisition price of $26,500 per year, they will require an accurate diagnostic test to guide physician prescribing and assess the challenging risk-benefit profile.

Diagnostic Accuracy of AD Matters:  

According to the Alzheimer’s Association, 50-70% of symptomatic patients are misdiagnosed with AD in the generalist setting. While this number drops to 25%-30% in the specialty memory clinics, diagnostic accuracy is still a great unmet medical need. Interestingly, the primary reason cited: “…because routine cognitive screening is not performed and there is a lack of easily accessible, time- and cost-effective, and accurate diagnostic tools.”

Identifying appropriate candidates for treatment by first confirming the presence of AD in the primary care setting goes far beyond addressing the potential burden on the healthcare system. Safety is a major concern with this class of drugs and experts recommend that recipients be carefully monitored for signs of brain bleeding and swelling that occurred in some patients who received LEQEMBI in clinical trials. Those reactions may have contributed to the deaths of three people who were also on blood thinners, according to media reports. Monitoring would include periodic brain scans and neurological examinations, which might prove to be costly and very difficult for the majority of PCPs.

Early and Accurate Diagnosis of AD is Critical 

Even in the absence of DMTs, the ability to accurately diagnose AD in the generalist setting with DISCERN has been shown in published economic models to be cost neutral when adding DISCERN to the current diagnostic pathway.  

When clinicians reduce reliance on expensive and invasive tests such as PET scans and CSF punctures to identify AD, DISCERN can be cost saving. In a published clinical utility study, most PCPs were dissatisfied with the current diagnostic approach, citing the burden and subjectivity of the diagnostic tools.  

Need for Accurate Testing in Primary Care

Making the DISCERN test available and reimbursed in the primary care setting can address the need for an accurate, early diagnosis of AD for the use of these new DMTs. As noted in the indication for LEQEMBI, the first question to answer is if AD is present.  

The DISCERN test empowers primary care physicians to cost-effectively identify AD, avoiding unnecessary costs and reducing patient burdens of advanced tests to identify the presence of amyloid plaque in those patients where AD is not detected. If AD is detected, the next step is to determine if the patient is appropriate for LEQEMBI by assessing the presence of amyloid plaque.

What are the alternatives for treating Early Dementia or MCI? 

While amyloid plaques are pathologic hallmarks of the disease at autopsy, they have not been observed to closely correlate with the patients’ cognitive decline during life. A recent study demonstrated that 43% of 80-89 year olds had amyloid plaque present in their brains, but no cognitive decline. While amyloid plaque is a hallmark of disease at death, synaptic dysfunction and neuronal loss are correlated with cognitive deficits.   

An accurate diagnosis is critical for many reasons since the risk factors associated with the new drug are severe. As the Alzheimer’s Forum points out, families will want to know if the cause of MCI or dementia is AD – before taking the risks associated with this new class of drugs. These risks include infusion-related reactions and the brain edema and microhemorrhages known as ARIA, which are included in the FDA label warnings. In particular, the label urges caution when prescribing lecanemab to people on blood thinners. Blood thinners recently have been associated with three deaths in the Phase 3 open-label extension trial.   

This drug also represents a new cost-center for payers and may come with an added cost burden for patients. The ALZ Forum points to the need for three MRIs in the first 14 weeks of treatment, testing that piles on additional costs beyond the already steep price tag.  

There is a great deal of discussion surrounding what is the most effective approach to managing MCI, and while early intervention is critical to changing the course of disease, the appropriate intervention remains to be seen. 

In studies, less than 50% of people with MCI will progress to dementia over 10 years, let alone to AD dementia. Data presented at the Clinical Trials in Alzheimer’s Disease (CTAD) 2022 from the SMARRT and EXERT study have shown that addressing known risk factors as well as lifestyle interventions can stabilize cognitive loss over time in people with MCI.  

Step therapy that first addresses lifestyle and known risk factors in people experiencing cognitive decline, before adding DMTs that have thus far demonstrated modest efficacy and significant safety considerations may be the most cost-effective and safest approach to stemming the disease.

SYNAPS Dx (SDx): Industry Innovator in Accurate Diagnostic Testing for AD

Experts predict that the number of Americans living with AD could rise from 6 million to 13 million by 2050. Given the complexity of this disease, getting an accurate diagnosis is critical for ensuring that people get the right treatment as soon as possible.

The SDx team recognizes that clinicians need better tools to identify AD in people recently diagnosed with dementia, especially in early disease when patients and caregivers have the most options for treatment and ability to slow disease progression. 

The SDx team developed the DISCERN test to support a clinician’s definitive diagnosis of AD versus other forms of dementia, even in people recently diagnosed with dementia. Without an accurate diagnosis, it is challenging to administer treatment protocols and help families plan for the care of a loved one.

Read more about the science behind the DISCERN test, here

Contact Caroline Chambers at cchambers@cpronline.com for additional information.