Aduhelm and Down Syndrome Information

On June 7, 2021, the FDA approved the use of the drug aducanumab [trade name: Aduhelm] to treat persons with Alzheimer’s disease using its accelerated approval pathway.  According to information provided about the drug, "Aduhelm is an antibody that targets amyloid-beta. The antibody preferentially binds to the aggregated amyloid-beta. This is because it targets an epitope that is not normally accessible in the amyloid-beta monomer. Through this interaction, Aduhelm could reduce the number of amyloid plaques present in the brain, potentially slowing neurodegeneration and disease progression." [source: Alzheimer's News Today]

In spite of the recognition by the National Institute of Health of Down syndrome as a high risk factor for Alzheimer's disease, no adults with Down syndrome (or with any other intellectual disability) were included in the original clinical trials that were undertaken by Biogen..  Thus, questions have been raised whether aducanumab can help adults with Down syndrome and other types of intellectual disability.  Questions have also arisen as the practicalities and logistics issues. These questions involve consideration of:

  • What may be any possible adverse effects from the drug?

  • How it may be best administered to adults who may not tolerate monthly hospital visits?

  • What will be the diagnostic process for determining eligibility for atypical adults?

  • What may be the optimal dosage variance for adults with Down syndrome compared to other adults?

  • Whether insurers will consider adults with Down syndrome eligible for coverage?

  • What equity considerations will be supported by DHHS and the Courts?

  • Whether there will be financial aid for families due to the annual cost of the drug?

  • How will ancillary costs (pre-prescription PET scans and assessments and post-procedure associated surveillance) be covered for families of adults with Down syndrome?

  • Will state developmental disabilities agencies be required to initiate referrals for assessments and provide coverage for treatment for adults in their services?

  • Will there be funding to support specialized intellectual disability assessment centers equipped with infusion chairs and able to provide regular M.R.I. scans to track any potential side effects?

  • Will there be specialized training of hospital personnel at clinics with infusion chairs about the special needs of adults with Down syndrome?

  • How will family support groups be funded and managed for families whose off-springs with Down syndrome are participating in Aduhelm treatments?

  • Will there be time limits on prescriptions for Aduhelm treatments once dementia is determined to be advancing?

  • Will centers with infusion chairs and other supports set triage parameters on the type and number of adults they will treat?

  • What will be the parameters of informed consent by adults with Down syndrome to obtain use of the drug?

  • What has to be done to include adults with Down syndrome in any subsequent clinical trials?

  • What may be the measures of drug efficacy for most adults with Down syndrome and within what timelines given the syndrome-specific compression of the effects of Alzheimer's?

  • What point will adults with Down syndrome be eligible for receipt of the drug (that is, will it be able to used as a prophylactic given the inherent risk for Alzheimer's among adults with Down syndrome)? 

At this point, it is known that the original clinical trials of aducanumab did not include any participants with Down syndrome or and adults with other forms of intellectual disability and nor were biomarkers used to screen to ensure that those in the study could be diagnosed with Alzheimer's disease.  The FDA's accelerated approval did not require biomarker confirmation and only requires a baseline and followup MRIs. No information is available on consideration of persons with natural early presence of plaques but not overt signs of dementia.The approved outcome is based on clearance of amyloid and does not particularly focus on the cognitive outcomes as which were indeed followed and measured in the original Biogen studies. The rate and risk of amyloid-related imaging abnormalities (ARIA) are very prevalent, which is not surprising since the monoclonal antibody is clearing amyloid and as a result the central nervous system (CNS) is reacting. The propensity and additional risk for micro-hemorrhages is expected in many people with Alzheimer's disease and this risk increases with the administration of Aduhelm and potentially is also dependent of the titration of the drug over the months of usage.

 

This preliminary knowledge raises many questions about the use of the drug with respect to its use with adults with Down syndrome.

The NTG is joining with other interested organizations in examining the scientific basis for the prescription for and treatment by Aduhelm among adults with Down syndrome.  Preliminary discussions among scientific and medical colleagues are being held and we have also opened discussions with Biogen. To this end, Dr. Seth M. Keller, the co-President of the NTG, is leading an effort to issue a collaborative scientific statement regarding the issues surrounding the use of aducanumab by adults with Down syndrome. Once that statement is completed and available we will post it on this site.

In the mean time, we are assembling what background information is available and posting it on this page.

FDA statement on approval of Aduhelm

        Official statement from FDA re: its accelerated pathway approval of Aduhelm

NIH statement on approval of Aduhelm

        Official NIH statement re: Adehelm

LuMind IDSC Foundation statement on Aduhelm and Down syndrome

        Initial statement regarding Aduhelm's use with adults Down syndrome

Biogen prescribing information for use of Aduhelm

        Prescription protocol for use of Aduhelm issued by Biogen

Information about how Aduhelm works and the Biogen clinical trials

        Brief web article on Biogen's clinical trials

AlzForum commentary on clinical trials

        Web article summarizing the technical information re: clinical trials for aducanumab

New York Times article on 'F.D.A. Approves New Medication for Alzheimer's' (6/8/21)

        Detailed description of aducanumab, issues related to its clinical trials, and other factors

New York Times article on 'Profit Spigot For Biogen May Be Tap on Medicare' (6/9/21)

        Detailed narrative of insurance issues for families with a member receiving Aduheim

Washington Post article on 'Furor Rages over FDA Approval of Controversial Alzheimer’s Drug (6/18/21)

        Commentary on perspective of critics and defenders with analysis of potential costs

Commentary on applications of Aduhelm for adults with Down syndrome

 Pending (article in preparation)

AADMD Position Statement:

"The AADMD's position regarding the prescription and use of all drugs that have been evaluated by the FDA's accelerated approval pathway (which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious life-threatening illness) is that their use should be a shared decision made by a physician, the patient, and any other significant and bona fide contributors to the decision-making process.  As additional information and evidence regarding the drug's safety and efficacy is made available, its applicability to distinct groups of adults (e.g., special populations such as adults with Down syndrome) may receive a definitive endorsement by the AADMD. Until that information is made available, we counsel caution and careful assessment as to whether the drug’s use would be safe and beneficial.  As a matter of policy, the AADMD encourages and supports the ethical and appropriate representation of "special populations" in all clinical trials designed to evaluate the safety and efficacy of any drugs for use with specific populations and recommends that the FDA require the inclusion of adults from distinct groups in any further clinical trials."  (Draft v. 6/8/21)