This post was originally published on this site
At this writing three members of the FDA Advisory Committee have chosen to resign in protest over the Food and Drug Administration’s decision to approve aducanumab for the treatment of mild cognitive impairment. Their decision to resign is commendable for at least three ethical reasons.
- Billions of Medicare dollars will be unjustly squandered on a drug of unknown effectiveness.
- Physicians must either facilitate this unjust squandering or deny desperate patients access to this drug.
- Patients have false hopes cruelly legitimated when physicians prescribe aducanumab.
However, more is needed than these resignations. I would recommend a much stronger response, which the Centers for Medicare and Medicaid Services could implement, namely, limiting reimbursement for aducanumab to actual production costs plus a small profit.
Billions in unjust profits
The FDA is requiring Biogen
BIIB,
to conduct a Phase 4 trial of aducanumab as a way of determining whether aducanumab yields any substantial benefit. That trial could take as long as nine years to complete. Meanwhile, Biogen would reap tens of billions in profits for a drug that current evidence suggests is of both uncertain value and uncertain efficacy. What is at stake?
“
Such desperation should be acknowledged, but false hopes should not be encouraged. Generating false hopes is both cruel and unaffordable.
”
There are 6.2 million Americans diagnosed with some degree of Alzheimer’s who are over age 65. Roughly half of them currently have mild cognitive impairment. These are the individuals who would potentially benefit from aducanumab. Biogen has indicated that aducanumab will have an average price of $56,000 a year. Given that 3.1 million individuals with mild Alzheimer’s over age 65 would all be eligible for Medicare coverage, the potential cost to Medicare a year would be $173 billion.
Aducanumab is given by monthly infusion. Roughly 40% of patients on higher doses of aducanumab experienced brain swelling or small vessel brain bleeds. This requires either MRI or PET brain scans to monitor these potential side effects on a regular basis for at least the first year of treatment. Consequently, the first-year additional costs for the infusions and brain scans are estimated to be $30,000 per patient, or an additional $93 billion in potential costs to Medicare. That figure would be reduced by 50% for each subsequent year of treatment.
This squandering of Medicare resources is what is at stake, given that FDA decision.
Aducanumab does reduce β-amyloid plaque in the brain. Advocates for the drug contend that this is a reasonable basis for concluding that the drug is clinically effective. Critics point out that several prior drugs have reduced amyloid in the brain with no more than marginal and temporary cognitive improvement.
Dr. David Knopman, who resigned from the advisory committee and who is a clinical neurologist at the Mayo Clinic, is quoted as saying, “Biomarker justification [reduced amyloid] for approval in the absence of consistent clinical benefit after 18 months of treatment is indefensible.” What can be done?
Limit reimbursement
I would propose limiting reimbursement for the drug to the actual cost of drug production: no marketing costs, no research costs, no executive salary costs, no inflated overhead. I would add 5% as a profit margin. That number would likely be in the $2, 000 to $5,000 range.
Biogen would have the opportunity to determine whether the drug is significantly clinically effective without putting Medicare finances and taxpayer resources at risk for a drug that has not been able to prove itself thus far to provide meaningful clinical benefit. Critics will still see this as a waste of resources. In fairness, critics do not know with certainty that this is the case.
Biogen now says it plans to complete ‘confirmatory’ study for Alzheimer’s drug earlier than required
We can readily imagine the message that Biogen and the Alzheimer’s Association will craft to propel demands for aducanumab among patients and families who see themselves as being at risk for advancing Alzheimer’s dementia. Such desperation should be acknowledged, but false hopes should not be encouraged. Generating false hopes is both cruel and unaffordable. Providing very limited reimbursement for the drug would yield access to the drug for desperate patients and families without unjustly squandering Medicare resources.
I recognize this proposal will create a significant burden for clinicians caring for these patients. They will need to be especially careful in conveying to patients the risks of brain swelling and small vessel brain bleeds for the very small and uncertain benefits that research with aducanumab has demonstrated so far. This is an ethical bind for physicians that must not be ignored. Seeming to support false hopes is both harmful and unjust.
Finally, I imagine Biogen will not welcome this proposal. However, it would certainly motivate speedier effort to complete a Phase 4 trial. Also, if the trial were successful enough, any years lost on the patent clock could be restored. If the trial were not successful, the drug would be removed from the market. There are other drugs similar to aducanumab in the pipeline, such as Eli Lilly’s
LLY,
donanemab.
My proposal would establish an important precedent for those pharmaceutical companies. They could expect the same crimped profits (and potential revenue losses from accrued research expenses) if they could not prove decisively that their drug yielded substantial clinical benefit at a reasonable cost. This would be a memorable lesson.
Leonard M. Fleck, Ph.D., is a professor at the Center for Bioethics and Social Justice in the College of Human Medicine at Michigan State University. This commentary is based on his article in the Hastings Center Journal, “Alzheimer’s and Aducanumab: Unjust Profits and False Hopes.”
From Barron’s: Biogen Stock Is Sliding. House Committees Will Investigate Its $56K Alzheimer’s Drug.
From MarketWatch: Lilly to seek FDA approval for potential Alzheimer’s drug later this year
From The Wall Street Journal: Costly New Alzheimer’s Drug Could Force Medicare to Restrict Access
