Aducanumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetAmyloid beta
Clinical data
Trade namesAduhelm
Other namesAducanumab-avwa, BIIB037, BIIB-037
AHFS/Drugs.comMonograph
License data
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life24.8 days[3]
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6472H10028N1740O2014S46
Molar mass145912.34 g·mol−1

Aducanumab, sold under the brand name Aduhelm, is a medication designed to treat Alzheimer's disease (AD).[2][3] It is a monoclonal antibody[2][3] that targets aggregated forms (plaque)[4][5] of amyloid beta (Aβ) found in the brains of people with Alzheimer's disease to reduce its buildup.[6][7] It was developed by Biogen and Eisai.[8] Aducanumab is given via intravenous infusion.[3]

Aducanumab was approved for medical use in the United States by the Food and Drug Administration (FDA) in June 2021,[9] in a controversial decision that led to the resignation of three advisers to the FDA in the absence of evidence that the medication is effective.[10][11][12] The FDA stated that it represents a first-of-its-kind treatment approved for Alzheimer's disease and that it is the first new treatment approved for Alzheimer's since 2003.[2] Aducanumab's approval is controversial for numerous reasons including ambiguous clinical trial results regarding efficacy, the high cost of the medication and the very high rate of serious adverse events.[13][12] The FDA considers it to be a first-in-class medication.[14]

In November 2020, a panel of outside experts for the FDA concluded that a pivotal study of aducanumab failed to show strong evidence that the medication worked, citing questionable efficacy and multiple red flags found with the data analysis.[15] There were also significant health risks associated with the medication; brain swelling or brain bleeding was found in 41% of patients enrolled in the studies.[16] Nevertheless, the medication was approved under the FDA's accelerated approval pathway, and the FDA requires Biogen to perform follow-up reviews to assure the medication is a safe and effective treatment for Alzheimer's disease.[2][17] The Office of Inspector General, US Department of Health and Human Services was asked to investigate interaction between the drug company and the FDA prior to the medication's approval.[18]

Biogen abandoned the drug in January 2024, for financial reasons.[19]

Medical uses

In the US, Aducanumab is indicated for the treatment of Alzheimer's disease.[2][3] In July 2021, the US Food and Drug Administration (FDA) limited the indication to people with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.[3]

Mechanism of action

Main article: Biochemistry of Alzheimer's disease § Amyloid hypothesis

Aducanumab is a monoclonal IgG1 antibody that binds to the amyloid beta protein at amino acids 3–7, which is posited to result in slowing the progression of Alzheimer's disease.[5] The mechanism is based on the amyloid hypothesis, which posits that amyloid proteins cause AD, hence removing amyloid should slow the progression of the disease.[7]

How the antibody accesses the plaques is under active research. One mechanism suggests the plaques are exposed to the lumen of a blood vessels and the antibody accesses the plaques from the lumen side.[20] This assumes the plaque formed as a result of a leaky blood brain barrier and may also explain why there is hemorrhage after the plaques are removed.[21]

Adverse effects

The most common serious adverse reactions reported are:[3]

History

Aducanumab was developed by Biogen Inc., which licensed the medication candidate from Neurimmune, who discovered it with the University of Zurich.[22][23]

Clinical trials

Interim results from the second phase I study of the medication were reported in March 2015.[24]

A phase Ib study was published in August 2016, based on one year of "monthly intravenous infusions" of aducanumab, which brain scans to measure amyloid plaques.[5] Phase II trials were not required by the FDA and were not conducted by Biogen, a decision that received criticism from some experts.[25][26]

Phase III clinical trials were ongoing in September 2016,[5] but were canceled in March 2019, after preliminary data from two phase III trials suggested it would not meet the primary endpoint.[27][28][29] While imaging studies had shown that aducanumab did reduce amyloid plaque buildup, a surrogate endpoint for Alzheimer's treatment,[30][31] it had not meaningfully met its primary endpoints with regards to cognitive function and mental decline.[32]

On 22 October 2019, Biogen announced that it would be restarting the FDA approval process for aducanumab stating that analysis of a larger dataset from its Phase 3 trials[33][34][35] showed that the drug reduced clinical decline in patients with early Alzheimer's disease when given at higher doses.[36] In one trial, "EMERGE",(NCT02484547), an analysis split by dose indicated that high doses reduced rate of decline by 22% versus placebo. However, an identical trial, "ENGAGE", failed to replicate this, with a non-significant 2% reduction in decline compared to placebo. Researchers had theorized that the difference may have stemmed from a change in protocol which affected more of the participants of the later study EMERGE than the earlier ENGAGE study's participants.[30][37][38] The FDA accepted Biogen's aducanumab Biologics License Application (BLA) on 7 August 2020 with a Priority Review.[39]

FDA review and approval

In November 2020, a panel of outside experts on the FDA's Peripheral and Central Nervous System Advisory Committee concluded that a pivotal study of aducanumab failed to show "strong evidence" that the medication worked, along with potential safety issues, and suggested that the FDA not approve aducanumab, citing questionable efficacy and multiple "red flags" found with the data analysis.[15][13]

Aducanumab was approved for medical use in the United States on 7 June 2021,[2][9][17] and was the first Alzheimer's treatment to receive approval through an accelerated pathway.[40]

Coverage in the United States

The Center for Medicare and Medicaid Services (CMS) finalized a coverage decision for aducanumab in April 2022. Coverage for aducanumab will be limited to individuals participating in randomized controlled trials to confirm the efficacy and safety for the Medicare population.[41][42]

European review

Aducanumab was rejected for medical use in the European Union in December 2021, by the European Medicines Agency (EMA).[43][44][45] In April 2022, Biogen withdrew its application for a marketing authorization of aducanumab (Aduhelm) for the treatment of Alzheimer's disease.[46]

Abandonment

In March 2022, Eisai relinquished full control over marketing decisions to Biogen, retaining only rights to partial royalties.[8]

In January 2024, Biogen announced that for financial reasons, it was terminating the post-marketing clinical study (called "ENVISION), abandoning commercial development of Aduhelm, terminating its lease of patent rights from Neurimmune, and redirecting resources to its other Alzheimer's treatments.[47] Availability was expected to continue for existing commercial patients until November, 2024.[48]

Society and culture

Efficacy

The June 2021 approval of the medication by the US Food and Drug Administration (FDA) was controversial because clinical trials gave conflicting results on its effectiveness.[13][15][49][50][51] Specific criticisms of the approval included: insufficient evidence of efficacy, that the drug offers false hope, and that the high cost will adversely impact patient finances and Medicare budget.[52][13]

Ten of the eleven outside experts that had served on the FDA's Peripheral and Central Nervous System Advisory Committee voted in November 2020 against approving aducanumab.[11][12][49][53] Soon after the approval was announced in early June 2021, three of the panelists who had voted against aducanumab's approval resigned in protest.[11][49][53][54][55] One of the resigning panelists said that the FDA move was "probably the worst drug approval decision in recent US history".[11][56]

Process concerns

Public Citizen[57] and the Institute for Clinical and Economic Review criticized the approval.[58]

Senator Joe Manchin heavily criticized the decision and said that the acting director of the FDA, Janet Woodcock, "should be quickly replaced."[59] According to The New York Times, the review process for the medication "took several unusual turns, including a decision for the FDA to work far more closely with Biogen than is typical in a regulatory review."[60] According to a 2022 report released by two House committees,[61] FDA and Biogen worked in concert to receive accelerated approval at a cost to patients of $56,000 a year.[62]

A 29 June 2021 STAT article reported that in the months prior to Aducanumab's FDA approval, FDA officials had met with "Biogen executives" using "back channels".[63][64]

On 9 July 2021, the FDA's Acting Commissioner, Janet Woodcock, requested that the Office of Inspector General, US Department of Health and Human Services conduct an independent review of interactions between FDA officials and Biogen representatives prior to the FDA's 27 June approval of aducanumab.[18][63] It was reported in August that the OIG will also investigate the "accelerated approval pathway, the regulatory mechanism" the FDA used to approve Aducanumab in spite of "conflicting data over whether it could actually slow Alzheimer's patients' mental decline."[65]

Patient advocacy groups had lobbied heavily for the approval of the medication for a debilitating condition with very few therapy choices.[51] Advocacy groups such as Alzheimer's Association,[66] Alzheimer Society of Canada,[67] and Alzheimer's Foundation of America[68] were also in favor of the decision. Alzheimer's Association denies their support for aducanumab was influenced by the at least $1.4 million they received since 2018 from Biogen and Eisai.[69]

In December 2022, a Congressional investigation by the House Committee on Oversight and Reform and the House Committee on Energy and Commerce was released that found the FDA had broken its own protocols in reviewing and approving aducanumab. The investigation found that the FDA had held unreported meetings and failed to gain internal consensus before engaging in collaboration with the drugmaker. The FDA also gave the medication a broad label, allowing it to be used on all Alzheimer's patients regardless of severity, even though it had only been tested on people with early Alzheimer's and mild symptoms. The report also questioned the agency's decision to abruptly switch from the traditional approval pathway to the accelerated approval pathway to grant approval in the medication's label to a broad patient population.[70]

The investigation further reported concerns related to Biogen's "aggressive launch and marketing plans." They obtained documents that show the company estimated a peak revenue of $18 billion per year with an initial price of $56,000 for patient treatment per year, despite what the Committees described as "a lack of demonstrated clinical benefit in a broad population." Documents show that Biogen estimated aducanumab would cost the Medicare program $12 billion a year and that Medicare patients would incur out-of-pocket costs that could account for as much as 20% of their income.[61] Aware that the high price would trigger "pushback" from payers and providers, "Biogen developed an external narrative about the drug's value to sell to the patients and the public." According to the report, Biogen knew its $56,000 launch price was "unjustifiably high," but company executives wanted to "make history" and "establish Aduhelm as one of the top pharmaceutical launches of all time." Findings showed that Biogen estimated that from 2020 to 2024, it would spend more than $3.3 billion on sales and marketing,[70] more than twice the development costs of the drug.[71]

Economics and cost

See also: Lecanemab § Economics

Treatment using aducanumab is estimated to cost US$56,000 per year, and Biogen's CEO stated that they would maintain this price for at least four years.[72][73] In their 10 June 2021 article, Kaiser Family Foundation (KFF) researchers said that a conservative estimate of the cost to Medicare would be $USD29 billion in one year. This is based on 500,000 Medicare patients potentially receiving Aduhelm. To put this in perspective—in 2019, "total Medicare spending for all doctor-administered drugs reached $37bn."[74][75] For patients with applicable health insurance and/or Medicare, the drug is a Tier 5 Specialty drug.[76][77] and the copayment for such therapy would be about $11,500 annually.[78][11] An initial brain positron emission tomography (PET scan) is required to detect the presence of amyloid beta; since 2013, it has not been covered by Medicare,[79][80] and as of 2018, can cost $2,250 – $10,700.[81] In November 2021, the Centers for Medicare and Medicaid Services (CMS), announced a 14% increase in Medicare Part B premiums for 2022 in response to the expected cost of Aduhelm.[82] A 15 July 2021 article in The Economist reported that the annual price of Aduhelm and the controversial 2021 FDA approval process resulted in the launch of an investigation by the United States House of Representatives, the Committee on Oversight and Reform, and the Committee on Energy and Commerce, making Aduhelm the "poster-child" for the Elijah Cummings Lower Drug Costs Now Act (H.R.3) campaign.[75][72] By December 2021, Biogen announced a 50% price cut for Aduhelm, from $56,000 to $28,200; this would have no impact on the cost of brain scans.[83]

Sales

Sales of the medication are far lower than analyst's predictions.[84] As of September 2021, only about 100 patients had received the drug,[84] far short of the 10,000 that would be needed by the end of 2021 to meet Wall Street expectations for Biogen's revenue.[85]

Names

Aducanumab is the international nonproprietary name.[86]

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  2. ^ a b c d e f g "FDA Grants Accelerated Approval for Alzheimer's Drug". U.S. Food and Drug Administration (FDA) (Press release). 7 June 2021. Archived from the original on 8 June 2021. Retrieved 7 June 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  3. ^ a b c d e f g h i j k l m n o "Aduhelm- aducanumab injection, solution". DailyMed. Archived from the original on 14 June 2021. Retrieved 14 June 2021.
  4. ^ Walsh S, Merrick R, Milne R, Brayne C (July 2021). "Aducanumab for Alzheimer's disease?". BMJ. 374: n1682. doi:10.1136/bmj.n1682. PMC 8258645. PMID 34226181.
  5. ^ a b c d Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, et al. (September 2016). "The antibody aducanumab reduces Aβ plaques in Alzheimer's disease". Nature. 537 (7618): 50–56. Bibcode:2016Natur.537...50S. doi:10.1038/nature19323. PMID 27582220. S2CID 205250312.
  6. ^ Abyadeh M, Gupta V, Gupta V, Chitranshi N, Wu Y, Amirkhani A, et al. (2021). "Comparative Analysis of Aducanumab, Zagotenemab and Pioglitazone as Targeted Treatment Strategies for Alzheimer's Disease". Aging and Disease. 12 (8): 1964–1976. doi:10.14336/AD. PMC 8612603. PMID 34881080.
  7. ^ a b Toyn J (May 2015). "What lessons can be learned from failed Alzheimer's disease trials?". Expert Review of Clinical Pharmacology. 8 (3): 267–269. doi:10.1586/17512433.2015.1034690. PMID 25860157. S2CID 35158630.
  8. ^ a b Liu A (15 March 2022). "Biogen takes full control of troubled Aduhelm in revamped Eisai deal". Fierce Pharma. Archived from the original on 21 March 2022. Retrieved 21 March 2022.
  9. ^ a b "Drug Approval Package: Aduhelm (aducanumab-avwa)". U.S. Food and Drug Administration (FDA). 22 June 2021. Archived from the original on 2 September 2021. Retrieved 1 September 2021.
  10. ^ Mahase E (June 2021). "Three FDA advisory panel members resign over approval of Alzheimer's drug". BMJ. 373: n1503. doi:10.1136/bmj.n1503. PMID 34117086. S2CID 235405355.
  11. ^ a b c d e "3 Experts Have Resigned From An FDA Committee Over Alzheimer's Drug Approval". NPR. 11 June 2021. Archived from the original on 11 June 2021. Retrieved 11 June 2021.
  12. ^ a b c Belluck P, Robbins R (10 June 2021). "Three F.D.A. Advisers Resign Over Agency's Approval of Alzheimer's Drug". The New York Times. Archived from the original on 14 November 2021. Retrieved 14 June 2021.
  13. ^ a b c d McGinley L (22 June 2021). "FDA releases fresh details on internal debate over controversial Alzheimer's drug". The Washington Post. Archived from the original on 19 November 2021. Retrieved 24 June 2021.
  14. ^ Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  15. ^ a b c Marchione M, Perrone M (6 November 2020). "FDA panel urges rejection of experimental Alzheimer's drug". Associated Press. Archived from the original on 17 November 2021. Retrieved 8 June 2021.
  16. ^ Belluck P (22 November 2021). "Concerns Grow Over Safety of Aduhelm After Death of Patient Who Got the Drug". The New York Times. ISSN 0362-4331. Archived from the original on 20 July 2022. Retrieved 20 July 2022.
  17. ^ a b "FDA's Decision to Approve New Treatment for Alzheimer's Disease". U.S. Food and Drug Administration (FDA). 7 June 2021. Archived from the original on 8 June 2021. Retrieved 7 June 2021.
  18. ^ a b Gumbrecht J (9 July 2021). "Acting FDA commissioner calls for independent investigation into approval of Alzheimer's drug". CNN. Archived from the original on 13 August 2021. Retrieved 1 September 2021.
  19. ^ "Biogen will stop selling its controversial Alzheimer's drug Aduhelm". ABC News. Retrieved 1 February 2024.
  20. ^ Hansen SB, Wang H (September 2023). "The shared role of cholesterol in neuronal and peripheral inflammation". Pharmacology & Therapeutics. 249: 108486. doi:10.1016/j.pharmthera.2023.108486. PMID 37390970. S2CID 259303593.
  21. ^ Hansen SB (18 July 2023). "Cholesterol's Function and Origin in the Alzheimer's Disease Brain". Journal of Alzheimer's Disease. 94 (2): 471–472. doi:10.3233/JAD-230538. PMID 37393509. S2CID 259307724.
  22. ^ Zacks R (20 November 2007). "Biogen Inks $380 Million Deal with Swiss Company". Xconomy. Archived from the original on 30 October 2019. Retrieved 18 August 2015.
  23. ^ "Approval for New Alzheimer's Drug Developed at UZH". University of Zurich. 7 June 2021. Archived from the original on 17 November 2021. Retrieved 16 November 2021.
  24. ^ Sevigny J, Chiao P, Williams L, Chen T, Ling Y, O'Gorman J, et al. (July 2015). "O4-04-05: Aducanumab (BIIB037), an anti-amyloid beta monoclonal antibody, in patients with prodromal or mild Alzheimer's disease: Interim results of a randomized, double-blind, placebo-controlled, phase 1b study". Alzheimer's & Dementia. 11 (7S_Part_6): P277. doi:10.1016/j.jalz.2015.07.367. S2CID 54339030.
  25. ^ Karlawish J (30 May 2021). "If the FDA approves Biogen's Alzheimer's treatment, I won't prescribe it". STAT. Archived from the original on 7 June 2021. Retrieved 7 June 2021.
  26. ^ Belluck P, Robbins R (5 June 2021). "Alzheimer's Drug Poses a Dilemma for the F.D.A." The New York Times. Archived from the original on 19 November 2021. Retrieved 7 June 2021.
  27. ^ Ducharme J (21 March 2019). "Biogen Halts Promising Alzheimer's Drug Trials Due to Disappointing Results". Time. Archived from the original on 2 June 2019. Retrieved 21 March 2019.
  28. ^ Li Y (21 March 2019). "Biogen posts its the worst day in 14 years after ending trial for blockbuster Alzheimer's drug". CNBC. Archived from the original on 7 June 2021. Retrieved 21 March 2019.
  29. ^ Annett T. "Biogen Plunges More Than 25 Percent on Alzheimer's Setback". Bloomberg News. Archived from the original on 8 June 2021. Retrieved 6 December 2019.
  30. ^ a b McNamara D (28 May 2020). "Mixed Results for Aducanumab in Two Phase 3 AD Trials". Medscape. Archived from the original on 8 June 2021. Retrieved 11 August 2020.
  31. ^ Manyara AM, Ciani O, Taylor RS (January 2022). "A call for better reporting of trials using surrogate primary endpoints". Alzheimer's & Dementia. 8 (1): e12340. doi:10.1002/trc2.12340. PMC 9323346. PMID 35910671.
  32. ^ "Biogen and Eisai to Discontinue Phase 3 ENGAGE and EMERGE Trials of aducanumab in Alzheimer's Disease". Biogen. 21 March 2019. Archived from the original on 13 October 2023.
  33. ^ Roberts M (22 October 2019). "First drug to slow Alzheimer's may be available soon". BBC News. Archived from the original on 5 December 2019. Retrieved 22 October 2019.
  34. ^ Foster L (26 October 2019). "Drug 'could be biggest Alzheimer's development'". BBC News. Archived from the original on 19 December 2019. Retrieved 26 October 2019.
  35. ^ Kunkle F (6 December 2019). "Biogen's potential new drug for Alzheimer's disease gets cautiously optimistic review following presentation". The Washington Post. Archived from the original on 2 January 2020. Retrieved 6 December 2019.
  36. ^ Howard J, Gumbrecht J (23 October 2019). "Drugmaker to seek approval for Alzheimer's treatment". CNN. Archived from the original on 24 August 2021. Retrieved 23 October 2019.
  37. ^ Herper M (22 October 2019). "In shocking reversal, Biogen to submit Alzheimer's drug for approval". Scientific American. Archived from the original on 5 April 2023. Retrieved 15 November 2023. In one study, called Emerge, patients on the high-dose aducanumab had a 23% reduction in their rate of decline compared to those on placebo; those who were on the low dose were 11% lower than placebo, but that result was not statistically significant. But in the second trial, Engage, the decrease was only 2% in patients on the high dose.
  38. ^ "Biogen Plans Regulatory Filing for Aducanumab in Alzheimer's Disease Based on New Analysis of Larger Dataset from Phase 3 Studies". Biogen. 22 October 2019. Archived from the original on 29 May 2020. Retrieved 22 October 2019.
  39. ^ "FDA Accepts BLA for Biogen's Alzheimer's Drug, Grants Priority Review". BioSpace. 7 August 2020. Archived from the original on 2 September 2021. Retrieved 1 September 2021.
  40. ^ Bell J (6 February 2023). "Eisai gives first glimpse into Alzheimer's drug launch". BiopharmaDive. Washington, D.C.: Informa. Archived from the original on 6 February 2023. Retrieved 11 February 2023.
  41. ^ "NCA - Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer's Disease (CAG-00460N) - Decision Memo". Center for Medicare and Medicaid Services. Archived from the original on 5 June 2022. Retrieved 9 June 2022.
  42. ^ "Medicare Officially Limits Coverage of Aduhelm to Patients in Clinical Trials". The New York Times. 7 April 2022. Archived from the original on 23 March 2023. Retrieved 9 July 2023.
  43. ^ "Refusal of the marketing authorisation for Aduhelm (aducanumab) EMA/112932/2022 Rev.1 / EMEA/H/C/005558" (PDF). European Medicines Agency (EMA). February 2022. Archived from the original on 17 December 2021.
  44. ^ "Aducanumab rejected in the EU: Biogen to ask EMA to re-examine application". biopharma reporter. 20 December 2021. Archived from the original on 20 December 2021. Retrieved 21 December 2021.
  45. ^ "Alzheimer's drug aducanumab not approved for use in EU". BBC News Online. 17 December 2021. Archived from the original on 21 December 2021. Retrieved 21 December 2021.
  46. ^ "Aduhelm: Withdrawn application". European Medicines Agency (EMA). 9 March 2023. Archived from the original on 10 July 2023. Retrieved 9 July 2023.
  47. ^ "Biogen to Realign Resources for Alzheimer's Disease Franchise". 31 January 2024.
  48. ^ Tom Murphy (31 January 2024). "Biogen will stop selling its controversial Alzheimer's drug Aduhelm". Associated Press.
  49. ^ a b c Ault A (5 May 2021). "FDA Reviewers: Why We Are Against Approval of Aducanumab for Alzheimer's". Medscape Medical News. Archived from the original on 10 June 2021. Retrieved 9 June 2021.
  50. ^ "US approves first new Alzheimer's drug in 20 years". BBC News Online. 7 June 2021. Archived from the original on 30 September 2021. Retrieved 7 June 2021.
  51. ^ a b Belluck P, Robbins R (7 June 2021). "F.D.A. Approves Alzheimer's Drug Despite Fierce Debate Over Whether It Works". The New York Times. Archived from the original on 14 November 2021. Retrieved 7 June 2021.
  52. ^ McGinley L (17 June 2021). "Furor rages over FDA approval of controversial Alzheimer's drug". The Washington Post. Archived from the original on 19 November 2021. Retrieved 19 June 2021.
  53. ^ a b "Third member of FDA expert committee resigns over Alzheimer's decision". STAT. 10 June 2021. Archived from the original on 2 September 2021. Retrieved 1 September 2021.
  54. ^ McGinley L (9 June 2021). "Two members of an FDA advisory committee quit after approval of controversial Alzheimer's drug". The Washington Post. Archived from the original on 10 June 2021. Retrieved 9 June 2021.
  55. ^ Langreth R (10 June 2021). "Harvard Expert Quits FDA Panel as Furor Over Biogen Drug Grows". Bloomberg. Archived from the original on 10 June 2021. Retrieved 10 June 2021.
  56. ^ "Harvard Expert Quits FDA Panel as Biogen Drug Furor Grows". Bloomberg. 10 June 2021. Archived from the original on 10 June 2021. Retrieved 1 September 2021.
  57. ^ "Statement: FDA's Decision to Approve Aducanumab for Alzheimer's Disease Shows Reckless Disregard for Science, Severely Damages Agency's Credibility". Public Citizen. 7 June 2021. Archived from the original on 11 June 2021. Retrieved 11 June 2021.
  58. ^ "ICER Issues Statement on the FDA's Approval of Aducanumab for Alzheimer's Disease". ICER. Archived from the original on 11 June 2021. Retrieved 11 June 2021.
  59. ^ Edney A (17 June 2021). "Key Democrat Manchin Bashes FDA Leader on Alzheimer's Approval". Bloomberg News. Archived from the original on 2 July 2021. Retrieved 20 June 2021.
  60. ^ Belluck P, Kaplan S, Robbins R (20 July 2021). "How Aduhelm, an Unproven Alzheimer's Drug, Got Approved". New York Times. Archived from the original on 4 August 2021. Retrieved 5 August 2021.
  61. ^ a b "The High Price of Aduhelm's Approval: An Investigation into FDA's Atypical Review Process and Biogen's Aggressive Launch Plans" (PDF). Committee on Energy and Commerce/Committee on Oversight and Accountability. December 2022. Archived (PDF) from the original on 31 December 2022. Retrieved 31 December 2022.
  62. ^ Johnson M (29 December 2022). "House investigation faults FDA, Biogen for Alzheimer's drug approval". The Washington Post. Archived from the original on 30 December 2022. Retrieved 31 December 2022.
  63. ^ a b Rosenbaum L (9 July 2021). "FDA Commissioner Calls For Inspector General Probe Into Biogen Alzheimer's Drug Approval". Forbes. Archived from the original on 19 November 2021. Retrieved 1 September 2021.
  64. ^ Feuerstein A, Herper M, Garde D (29 June 2021). "How Biogen used an FDA back channel to win Alzheimer's drug approval". STAT. Archived from the original on 2 September 2021. Retrieved 1 September 2021.
  65. ^ Jason M (4 August 2021). "HHS extends Aduhelm investigation into the accelerated approval pathway, wading into a brewing controversy". Endpoints News. Archived from the original on 2 September 2021. Retrieved 1 September 2021.
  66. ^ "It's a New Day in the Fight Against Alzheimer's — Aducanumab Approved". Alzheimer's Association. Archived from the original on 10 June 2021. Retrieved 11 June 2021.
  67. ^ "First new treatment for Alzheimer's disease approved in nearly two decades offers hope for people living with dementia". Alzheimer Society of Canada. 7 June 2021. Archived from the original on 10 June 2021. Retrieved 11 June 2021.
  68. ^ "Alzheimer's Foundation of America Statement on FDA Approving First New Alzheimer's Medication in Nearly 20 Years". Alzheimer's Foundation of America. 7 June 2021. Archived from the original on 11 June 2021. Retrieved 11 June 2021.
  69. ^ "Alzheimer's Association Denies Conflict in Aducanumab Support". Medscape. Archived from the original on 8 August 2022. Retrieved 8 August 2022.
  70. ^ a b Weixel N (29 December 2022). "House investigation faults FDA approval of Alzheimer's drug Aduhelm as 'rife with irregularities'". The Hill. Archived from the original on 4 January 2023. Retrieved 4 January 2023.
  71. ^ Jen Christensen (29 December 2022). "House investigation says FDA approval process of Alzheimer's drug was 'rife with irregularities'". CNN.
  72. ^ a b Cunningham PW (16 June 2021). "The Health 202: The pricey new Alzheimer's drug adds to the pressure for drug price controls". Archived from the original on 19 November 2021. Retrieved 1 September 2021.
  73. ^ "Biogen CEO: committed to gathering new data on FDA-approved Alzheimer's drug". 7 June 2021. Archived from the original on 7 June 2021. Retrieved 7 June 2021.
  74. ^ "FDA's Approval of Biogen's New Alzheimer's Drug Has Huge Cost Implications for Medicare and Beneficiaries". Kaiser Family Foundation (KFF). 10 June 2021. Archived from the original on 1 September 2021. Retrieved 1 September 2021.
  75. ^ a b "Aduhelm may not cure Alzheimer's, but it might help fix drug prices". The Economist. 15 July 2021. ISSN 0013-0613. Archived from the original on 1 September 2021. Retrieved 20 July 2021.
  76. ^ "How do drug tiers work?". Blue Cross Blue Shield of Michigan. Archived from the original on 15 June 2021. Retrieved 14 June 2021.
  77. ^ "What Medicare Part D drug plans cover". US Centers for Medicare & Medicaid Services. Archived from the original on 19 November 2021. Retrieved 14 June 2021.
  78. ^ "Medicare Copays For New Alzheimer's Drug Could Reach $11,500 Annually". NPR. Associated Press. 10 June 2021. Archived from the original on 10 June 2021. Retrieved 11 June 2021.
  79. ^ "National Coverage Analysis (NCA) Beta Amyloid Positron Emission Tomography in Dementia and Neurodegenerative Disease (CAG-00431N)". Centers for Medicare & Medicaid Services (CMS). 27 September 2013. Archived from the original on 28 June 2021. Retrieved 28 June 2021.
  80. ^ Foley KE, Lim D, Roubein R (15 June 2021). "New Alzheimer's drug could be 'devastating' for Medicare". Politico. Archived from the original on 27 June 2021. Retrieved 19 June 2021.
  81. ^ How much does a PET scan cost? Archived 24 June 2021 at the Wayback Machine. 31 July 2018. New Choice Health. Retrieved 19 June 2021
  82. ^ "Medicare's Coverage Decision for the New Alzheimer's Drug and Why It Matters". KFF. 14 January 2022. Archived from the original on 20 July 2022. Retrieved 20 July 2022.
  83. ^ Khandekar A (20 December 2021). "Biogen halves price of Alzheimer's drug to $28,200". Reuters. Archived from the original on 20 December 2021. Retrieved 20 July 2022.
  84. ^ a b Feuerstein A, Garde D (22 September 2021). "Biogen's Aduhelm sales slower than disclosed, forcing company to consider cost-cutting measures". Stat. Archived from the original on 17 December 2021. Retrieved 11 December 2021.
  85. ^ Higgins-Dunn N (22 September 2021). "Struggling with Alzheimer's launch, Biogen couldn't present 'clear case for growth' outside of Aduhelm". Fierce Pharma. Archived from the original on 11 December 2021. Retrieved 11 December 2021.
  86. ^ World Health Organization (2014). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 72". WHO Drug Information. 28 (3). hdl:10665/331112.

External links

Monoclonals for bone, musculoskeletal, circulatory, and neurologic systems
More
Categories