July 9, 2023: Alzheimer's Leqembi (lecanemab) fast facts; patient watchdogs react to approval; new drug for type 1; gout drug repurposed for heart health; study compares breathing techniques
Dear Readers,
Because last week's full FDA approval of Alzheimer's drug Leqembi (lecanemab) presents new treatment options and serious cost implications for millions of patients, we are providing this special report on lecanemab. Perspectives from U.S. patient watchdog groups and references to sources used for the compilation are provided at the bottom of the post.
Lecanemab Fast Facts
On July 6, the U.S. Food and Drug Administration (FDA) approved Eisai's supplemental drug application for Leqembi (lecanemab) monoclonal antibody treatment for early stage Alzheimer's disease. The new "traditional approval" designation means that Eisai met the conditions of its "accelerated approval" outlined in January 2023, although additional follow-up studies are still required. Leqembi's drug label was updated to provide revised safety and side effects information, including a boxed warning and additional clinical trials results. Here are some key facts about Leqembi (lecanemab) approval:
Why the FDA Approved it: In results from an 18 month (still ongoing) clinical trial, lecanemab appeared to slow declines in memory and thinking by about 27% compared with placebo (see section below on consumer group reactions for another perspective on this data). Also, MRI scans showed that the amount of amyloid plaque in the brain was reduced in patients using lecanemab vs. placebo. The FDA is requiring lengthy follow up studies, including a new registry-based, observational study.
How it Works: Lecanemab works by reducing amyloid plaques that form in the brain, a defining pathophysiological feature of Alzheimer's disease.
Who is Eligible to Take it: The drug may be taken by patients with Mild Cognitive Impairment (MCI) or mild dementia who ALSO have evidence of amyloid plaques in an MRI scan. Additional MRIs should be performed prior to the 5th, 7th, and 14th infusions. Caveat for Medicare Coverage: Patients and their physicians must participate in a registry that tracks their experience with the drug.
Dosage & Dosage Frequency: The recommended dosage is 10 mg per kg of patient weight. The drug is diluted in a solution and administered as an intravenous infusion over approximately one hour, once every two weeks.
Drug Interactions: Patients taking anticoagulants (blood thinning drugs like Warfarin or coumadin) were more likely to experience bleeding in the brain.
Side Effects: A new boxed warning on the drug label states that the most serious potential side effects risks are brain swelling and bleeding which it describes as Amyloid-related imaging abnormalities (ARIA). ARIA is often temporary and can also be asymptomatic. More frequent side effects include headache, infusion-related reactions, rash, cough, and nausea/vomiting. Read the complete revised drug label for full list of side effects:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269s001lbl.pdf
Cost per Patient: Annual price is set at $26,500, making it one of the most expensive drugs to be covered by Medicare Part B. Patients could face up to $6,600 in annual out-of-pocket costs for Leqembi even with Medicare coverage, according to a study published in the journal JAMA Internal Medicine. Premiums are also likely to rise for part B coverage.
Projected number of patients and total annual cost to Medicare: Eisai expects Leqembi to be taken by 100,000 individuals with Alzheimer's within the first three years, which would cost Medicare about $2.7 billion annually. However, that number of patients only represents about 1.5% of the estimated 6.7 million Americans with Alzheimer's. If the number of patients taking it grows to just 5% of Alzheimer's patients, Medicare expense will grow to a whopping $8.9 billion a year. To put this large dollar amount in perspective, in 2021, Medicare spent $40.1 billion on all drugs combined, according to KFF Health News.
Who makes it? Japanese company Eisai has partnered with U.S. company Biogen to manufacture the drug.
What other countries have approved lecanemab? Lecanemab has been submitted for approval in Japan, the European Union, China, Canada, Great Britain, and South Korea.
Additional Sources:
https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval
https://www.cnbc.com/2023/07/06/fda-approves-alzheimers-drug-leqembi-from-eisai-biogen.html
https://seekingalpha.com/news/3986276-biogen-eisai-leqembi-medicare-single-highest-drug-spend
View this four minute video (or read the transcript) from the National Institute on Aging on how Alzheimer's changes the brain:
Reactions from Consumer Groups
Many patients, physicians, and the world's largest Alzheimer's nonprofit, the Alzheimer's Association applauded the approval, but some patient watchdogs expressed disappointment.
Dr. Robert Steinbrook, director of Public Citizen’s Health Research Group, issued the following statement: "Although expected, the FDA’s decision to grant full approval for lecanemab to treat adult patients with Alzheimer’s disease is misguided and very disappointing. The evidence for the drug’s clinical benefits does not outweigh its substantial health risks. The fact that a black box warning for brain swelling and bleeding risks has been added to the prescribing information for lecanemab underscores the substantial safety concerns. Patients with Alzheimer’s disease and their families are understandably desperate for better treatments. When it approves drugs for Alzheimer’s disease with little or no benefit and significant health risks, the FDA fails patients and the public.”
https://www.citizen.org/news/fda-approval-of-lecanemab-leqembi-for-alzheimers-disease-fails-patients-and-the-public/
People's Pharmacy syndicated columnist, radio host, and pharmacologist Joe Graedon provided his take on the approval: "The media has made it seem as if the drug is a breakthrough" … “but a deep dive into the clinical trials data – shows that the benefits seem very minimal and the side effects, like brain swelling and bleeding are risky." Graedon explains why the 27% difference in cognitive performance touted by Eisai is not all that big of a difference in absolute terms. The patients who got the drug instead of placebo improved their score by 0.45 points on the CDR-SB (Clinical Dementia Rating–Sum of Boxes scale that is often used to gauge a patient's level of dementia) compared with the placebo. However, the CDR-SB is an 18 point scale with a score of 1 indicating very little cognitive decline while an 18 indicates severe dementia.
Patients began the study with a CDR-SB score of about 3.17 (very mild dementia). The CDR-SB score after 18 months of treatment was 4.38 on average for lecanemab-treated patients and 4.88 for placebo-treated patients, an average difference of .45 points on the scale. The previous drug (also by Eisai), aducanumab, disappointed scientists and it improved participants’ scores by 0.39 points on the same scale, which is not that different from the .45 improvement. Graedon points out that "a 0.45 difference between drug and placebo on an 18-point scale produces a lot less excitement" than a 27% reduction in memory decline.
https://www.peoplespharmacy.com/articles/is-new-dementia-drug-a-breakthrough-against-ad
This article provides more on CDR-SB:
Staging Dementia Using Clinical Dementia Rating Scale Sum of Boxes Scores"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409562/
If you think the data presented in press releases about lecanemab is confusing and/or misleads consumers into thinking the potential benefits are greater than they really are, there is hope that in the future companies will do a better job of explaining the results of their studies. The FDA recently issued non-binding guidance to industry on how to present clinical trials data in direct-to-consumer communications in a more understandable way. The guidance:
“Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer (DTC) Promotional Labeling and Advertisements.”
https://www.fda.gov/media/169803/download
More Drug Approvals
The FDA approved Biomarin Pharmaceutical's Roctavian, an adeno-associated virus vector-based gene therapy for the treatment of adults with a type of severe Hemophilia A. Hemophilia A is a rare genetic bleeding disorder that primarily affects males, causing affected individuals to bruise easily and have uncontrolled bleeding. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-adults-severe-hemophilia
The FDA approved Agepha Pharma's Lodoco (colchicine) pill to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular (CV) death in adult patients with established atherosclerotic disease or with multiple risk factors for CV disease. This approval represents a new indication for an old drug: colchicine was originally approved in 1961 and today is approved for gout flare-ups and to treat a rare hereditary condition called Familial Mediterranean fever. Paul Ridker, lead author of a recent Lancet study describing the role of inflammation in CV disease said, “To treat coronary disease effectively, cardiologists must aggressively reduce inflammation and cholesterol. For appropriate patients already taking a statin, adding the anti-inflammatory drug colchicine at a dose of 0.5 mg daily has been proven to significantly lower risks of recurrent heart attack and stroke.”
https://www.empr.com/home/news/lodoco-approved-to-reduce-risk-of-cardiac-events-in-patients-with-cardiovascular-disease/
The FDA approved CellTrans' Lantidra, the first cellular therapy made from deceased donor pancreatic cells for the treatment of type 1 diabetes. Lantidra is approved for the treatment of adults with type 1 diabetes who are unable to approach target glycated hemoglobin (average blood glucose levels) because of current repeated episodes of severe hypoglycemia (low blood sugar) despite intensive diabetes management and education.
The drug is given by infusion into the portal vein, which is the blood vessel that delivers blood to the liver. During the two clinical studies, 30 participants with Type 1 diabetes and hypoglycemic unawareness received between one and three infusions of Lantidra. Afterwards, 11 of them did not need insulin for one to five years and 10 of the participants did not have to take insulin for more than five years. Only 5 of the patients were not able to get rid of their insulin dependence for any length of time.
https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-type-1-diabetes
WXYZ Detroit News' Dr. Nandi explains how Lantidra works and describes its side effects (nausea, fatigue, anemia, and abdominal pain). Immune reactions are also a risk.
https://www.wxyz.com/news/fda-approves-new-cell-therapy-for-type-1-diabetes
Stressed? Try 5 minutes a day of "Cyclic Sighing"
For centuries, humans have used controlled breathing techniques as a way to reduce feelings of stress. However, little comparative data exist on the effects of different breathing techniques or the amount of breathing exercise that must be performed to produce those effects. Researchers at the Department of Psychiatry & Behavioral Sciences at Stanford University Medical School conducted a study to compare the psychophysiological effects of 5 minute long daily practice of three different breathing exercises and mindfulness meditation over 1 month.
Results showed that breath work improved mood and physiological arousal more than mindfulness meditation. Results also showed "Cyclic Sighing" to be the most effective breath work technique for improving mood and reducing respiratory rate. Go to the section of the paper called "Description of breathing protocols" to find out how to do each of the techniques, including "Mindful Meditation," "Cyclic Sighing," "Boxed Breathing," and "Cyclic Hyperventilation with Retention." This study was published in Cell Reports Medicine. Only 5 minutes of practice per day made a difference for some of the participants.
https://doi.org/10.1016/j.xcrm.2022.100895
Visit us at AskaPatient.com for drug ratings and reviews provided by patients along with more news and health information. Note to readers: Ask a Patient® Health News (general edition) will be sent on Tuesday, July 11. If you are not already subscribed to this separate newsletter, sign up today on our web site.