Manufacturer, VA Working Out Agreement to Provide Drug to Veterans
CAMBRIDGE, MA — Aducanumab, the novel Alzheimer’s drug that recently gained accelerated approval from the Food and Drug Administration is expected to cost about $56,000 a year. It is expected, however, that the price will be considerably less than that for the VA, which cares for tends of thousands of older veterans with cognitive deficits.
Biogen, the manufacturer of aducanumab, which is marketed as Aduhelm, said it is working to finalize a multiyear agreement in order to “support access for veterans throughout the VHA system.” A Biogen press release noted that the VHA is the largest integrated health system in the United States, with nine million enrolled veterans and that about 48% of them are older than 65.
A recent article in Frontiers in Psychiatry pointed out that the estimated dementia prevalence among VA patients age 65 and older is 9.6%, while a recent meta-analyses of dementia prevalence studies reported a similar pooled prevalence rate of 10.1% in the VA.
Furthermore, according to the authors from the Icahn School of Medicine at Mount Sinai in New York, and the James J. Peters VAMC in Bronx, NY, prevalence of dementia among veterans is expected to increase substantially in the coming decades. VHA’s Office of Policy & Planning has projected a 22% increase in the number of VA Patients with Dementia (276,000-335,000) between 2020 and 2033.
Biogen and its partner Eisai, noted, “The ethnically diverse population of U.S. veterans also faces increased risk for the disease as a result of their service, including conditions such as post-traumatic stress disorder, traumatic brain injury, and other factors.”
The companies said they are committed to addressing health equity for underserved and underrepresented populations that are at higher risk for Alzheimer’s disease, explaining, “Black/African Americans and Latinx people are disproportionally more likely to develop Alzheimer’s disease as well as more likely to have missed diagnoses compared to non-Hispanic white Americans.”
Whether other federal healthcare systems, such as Medicare or Medicaid, will pay for the drug or what the agreements will look like remains unknown, however. Aducanumab is expected to be available by the end of the year.
The FDA’s approval of aducanumab for the treatment of Alzheimer’s, a debilitating disease affecting 6.2 million Americans, was unprecedented in several ways.
Aduhelm is the first new treatment approved for Alzheimer’s since 2003 and is the first therapy that targets the fundamental pathophysiology of the disease, according to the FDA. It was approved using the accelerated approval pathway, used for drugs that treat serious or life-threatening illnesses and provide a meaningful therapeutic advantage over existing treatments.
Aducanumab is an antibody targeting amyloid-beta by preferentially binding to the aggregated precursor protein. The drug, which targets an epitope that is not normally accessible in the amyloid-beta monomer, is designed to reduce the number of amyloid plaques present in the brain, potentially slowing neurodegeneration and disease progression. Some of the research leading to approval was performed at the Ralph H. Johnson VAMC in South Carolina.
In a press release, FDA explained that accelerated approval “can be based on the drug’s effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients, with a required post-approval trial to verify that the drug provides the expected clinical benefit.”
Controversial Decision
Controversy about aducanumab, a monthly intravenous infusion, primarily centered on two issues: its effectiveness in slowing cognitive decline in people with mild memory and thinking issues and the high price.
To address the first issue, the FDA is requiring the company, Biogen, to conduct a new randomized, controlled clinical trial to verify the drug’s benefit. If that fails to occur or the trial doesn’t meet its endpoints, drug regulators can initiate proceedings to withdraw approval of the drug.
As for the second issue, Biogen, its manufacturer, has set the wholesale acquisition cost (WAC) of the drug at $4,312 per infusion for a patient of 74 kg–the average weight of a U.S. patient with mild cognitive impairment (MCI) or mild dementia. While yearly cost at the maintenance dose (10 mg/kg) would be $56,000, the cost during the first year of treatment would be lower due to the titration period, Biogen advised. On the other hand, healthcare systems also will have the cost of screening patients for access to the drug, which will require either a PET scan or lumbar puncture. In addition, patients will also need a baseline MRI within one year before treatment and two more exams prior to subsequent infusions.
Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, explained why the approval was made in the case of Aduhelm, noting, “Alzheimer’s disease is a devastating illness that can have a profound impact on the lives of people diagnosed with the disease as well as their loved ones. Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s. As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”
Alzheimer’s is an irreversible, progressive brain disorder that gradually destroys memory and thinking skills and functionality. The specific causes of Alzheimer’s disease are not fully known, but the disease is characterized by changes in the brain—including amyloid plaques and neurofibrillary, or tau, tangles—that result in loss of neurons and their connections.
In a separate website posting from the FDA’s press release, Cavazzoni addressed some of the controversy about the approval decision, writing, “We are well aware of the attention surrounding this approval. We understand that Aduhelm has garnered the attention of the press, the Alzheimer’s patient community, our elected officials, and other interested stakeholders. With a treatment for a serious, life-threatening disease in the balance, it makes sense that so many people were following the outcome of this review. Further, the data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit. There has been considerable public debate on whether Aduhelm should be approved. As is often the case when it comes to interpreting scientific data, the expert community has offered differing perspectives.”
He added, “At the end of the day, we followed our usual course of action when making regulatory decisions in situations where the data are not straightforward. We examined the clinical trial findings with a fine-toothed comb; we solicited input from the Peripheral and Central Nervous System Drugs Advisory Committee; we listened to the perspectives of the patient community; and we reviewed all relevant data. We ultimately decided to use the Accelerated Approval pathway—a pathway intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit. In determining that the application met the requirements for Accelerated Approval, the Agency concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy.”
That decision was based on three separate studies with a total of 3,482 patients. Results indicated that patients receiving the treatment had significant dose and time-dependent reduction of amyloid beta plaque, compared with those in the control arms who had no reduction of amyloid beta plaque.
“The need for treatments is urgent: Right now, more than six million Americans are living with Alzheimer’s disease, and this number is expected to grow as the population ages,” Cavazzoni emphasized.
- Zhu CW, Sano M. Demographic, Health, and Exposure Risks Associated With Cognitive Loss, Alzheimer’s Disease and Other Dementias in US Military Veterans. Front Psychiatry. 2021 Feb 25;12:610334. doi: 10.3389/fpsyt.2021.610334. PMID: 33716816; PMCID: PMC7947283.
