DISAJP NEWS Vol. 46 January 4th, 2022 ” ADUHELM® rejected in EU ”
This email is sent to those who subscribe DISA NEWS, the newsletter from the Dementia Improved Support Association of Japan.
We deliver the newsletter on the 4th of each month to bring you valuable information, aiming to achieve the dementia-free world.
Contents
〇 New year greetings from the Chief Executive Kazuo Naoi and Scientific Research Advisor Prof. Masao Mori
〇 Aduhelm rejected in EU reflecting future of dementia treatment
〇 Introduction of Matrix
〇 Latest news on dementia and its prevention
〇 100 things by Dr. Hasegawa, the developer of HDS-R
〇 What is KOUKA?
〇 International mail delivery of KOUKA
〇 New year greetings from the Chief Executive Kazuo Naoi and Scientific Research Advisor Prof. Masao Mori
Kazuo Naoi, Chief Executive
Happy New Year!
I sincerely wish you all happiness.
It takes time to be able to appreciate ordinary things.
That a gift you can receive only when you become mature.
“Born in the big rest,
We keep going taking small and sometimes medium rests,
Until the last when we return to the big rest.”
Michio Mado, a Japanese poet who received the Hans Christian Andersen in his life of 104 years
We look forward to your continued support.
Kazuo Naoi, Chief executive, Dementia Improved Support Association of Japan
Prof. Masao Mori, Scientific Research Advisor
Happy New Year!
I hope you had a good time in the turn of the year.
This year, we will keep going with extra momentum.
With COVID-19 becoming under control, things will get better.
I have a feeling that our plan will go right.
We are ready to put more focus on depression and dementia.
Let me finish this message with my wish for the world peace and development of our country.
Best wishes for your good health, long life and much success.
Prof. Masao Mori, Scientific Research Advisor, Dementia Improved Support Association of Japan
〇 Aduhelm rejected in EU reflecting future of dementia treatment
DECEMBER 20, 2021
Biogen Inc. (Nasdaq: BIIB) today announced that, effective January 1, 2022, it will reduce the wholesale acquisition cost (WAC) of ADUHELM® (aducanumab-avwa) 100 mg/mL injection for intravenous use in the United States by approximately 50%.
For a patient of average weight (74 kg), the yearly cost at the maintenance dose (10 mg/kg) will be $28,200.
Do you think this is a good news or not?
September 6, 2021
The U.S. Food and Drug Administration (FDA) approved Aduhelm (aducanumab) for a treatment of Alzheimer’s.
In Japan, a committee in the Ministry of Health, Labour and Welfare (MHLW) had a meeting to decide if the medicine should be approved or not on December 22, 2021, after a series of discussion during the year.
The First Committee on New Drugs (NDC) of the Pharmaceutical Affairs and Food Sanitation Council that advises MHLW decided to continue deliberations on the application for the manufacturing and marketing approval of aducanumab for the treatment of Alzheimer’s disease.
NDC concluded that they need to reexamine the efficacy and safety of the medicine and reconsider this matter according to the result, as clear judgement on the efficacy from current data is difficult.
■ Points of controversy
1. Two multicenter international phase III trials cited as the evidence are inconsistent.
2. Decrease of amyloid beta plaques in the brain, which is an exploratory outcome measure, has no established clinical significance.
3. Administration of Aduhelm caused cerebral edema and bleeding.
U.S. FDA ‘s approval for Aduhelm
The FDA’s decision was based on the drug’s ability to remove amyloid plaques, rather than any proven ability to slow the symptoms of Alzheimer’s.
Aduhelm is in a different league from previous products that came through accelerated approval, in terms of the number of potential patients and cost to the healthcare system.
The FDA’s approval ignored the recommendation of its outside advisors, who said Biogen did not provide enough evidence of clinical benefit.
Three of the advisory panel’s members have resigned in protest since the FDA decision was announced on June 7, 2021.
This action was an expression of their will against the decision ignoring patient’s safety and security along with malignant intentions (actually the stock price soared).
Fair and impartial data examination process
Any drug approval requires submission of data from clinical trials that shows efficacy and safety.
There are three phases in clinical trials:
– Phase I to examine safety through administration to healthy individuals
– Phase II to examine safety through administration to limited patients
– Phase III to examine efficacy through participation of many patients, comparing symptom progression of those who take the drug and not.
On Aduhelm, two phase III trials, ENGAGE and EMERGE, were conducted respectively from August and September in 2015.
In both trials, the drug was administered to those with mild dementia or mild cognitive dysfunctions for a year and a half.
Through the trials, the difference in long term progression between those who were administered and not was evaluated.
The evaluation forced the trial into suspension in March 2019, well before the completion.
The reason for the discontinuation was that the data didn’t showed clear difference between those administered and not.
To prevent unnecessary burden on trialists and risk of side effects, the drug makers decided to renounce their plan.
November 2020
FDA’s outside advisory panel concluded that Biogen did not provide enough evidence of clinical benefit.
The panel recommended FDA not to approve the drug, because of questions about efficacy emerged in data analysis and some danger signs.
Biogen and Eisai reclaimed that the drug should be approved because data on some groups showed the drug’s ability to prevent decline of the brain.
Accelerated approval program
The US drug approval system has a program called accelerated approval instituted in 1992.
According to this program, any drug can be used as a medical treatment if the possibility of the efficacy is shown, even if the efficacy itself isn’t shown.
However, further clinical trials need to be conducted after the approval to prove the efficacy.
The approval can be canceled if the efficacy isn’t proved afterward.
Accelerated approval was instituted for new drugs potentially effective to treat serious conditions including cancers that can’t wait for the completion of normal approval process.
Aduhelm failed to prove the preventative efficacy against Alzheimer’s, but succeeded in showing the ability to reduce amyloid beta.
That made FDA determine that the product met the requirement.
December 16, 2021
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the refusal of the marketing authorization for Aduhelm.
EMA noted that although Aduhelm reduces amyloid beta in the brain, the link between this effect and clinical improvement had not been established.
The committee also pointed out that two phase III trials were conflicting.
In addition, it decided that the studies didn’t show the medicine was sufficiently safe, as some patients showed Amyloid Related Imaging Abnormalities (ARIA).
Committee concluded that the benefits of Aduhelm did not outweigh its risks and recommended refusing marketing authorization.
This news made Biogen’s and Eisai’s stock prices fall by more than 40% since their peak in June.
https://www.bloomberg.com/news/articles/2021-12-17/biogen-alzheimer-s-drug-gets-negative-opinion-from-eu-regulator
On 17th, Biogen and Eisai announced that they would request redeliberations.
Although Japan and Europe have similar systems to the accelerated approval, there is much difference in the process, which made EU deny the claim by Biogen and Eisai.
The news above was followed by Eisai’s announcement on 20th, saying Biogen cut the price almost in half in the US.
This seems to be a tactic to get approval in Japan.
No treatment for dementia
June 1, 2018
The French Ministry of Health and Welfare (the Ministry of Social Issues and Health) announced that they would exclude medicines for Alzheimer’s treatment from health insurance.
The French Ministry of Health and Welfare announced that they would take out medicines for Alzheimer’s treatment from health insurance
The Ministry announced that Donepezil, Galantamine, Rivastigmine and Memantine would be excluded from the coverage of the country’s health insurance from August 1, 2018.
The four drugs were determined to be ineffective for treatment of dementia.
In Japan, those medicines are still widely administered in 2022, because they are the only approved medications.
On the other hand, we know many people whose peripheral symptoms became milder after quitting these drugs on their own discretion.
Clearly, those medicines have strong side effects rather than working as curatives for their mind and body.
November 2, 2019
Chinese authority conditionally approved Green Valley’s Oligomannate
Despite reported as a new hope for dementia treatment, Oligomannate hasn’t provided further news for so long.
At the release of the approval, our scientific advisor Prof. Masao Mori shared his view.
“Simply put, Oligomannate is a compound of oligosaccharide and sodium.
For about 20 years, Japanese medical community has also studied those substances causing physiological effects that help prevent lifestyle-related diseases.
It is clear that the compound is not harmful to human body.
Oligomannate is unlikely to have side effects like Donepezil, Galantamine, Rivastigmine and Memantine that actually boost BPSD rather than ameliorating it.
So it has low risk for Alzheimer’s patients with mild or moderate symptoms.
However, I presume it is difficult to prove that the drug suppresses the symptoms.”
2022 will be the year of KOUKA
FDA granted approval while EMA denied.
Anyway, Aduhelm should be able to reduce amyloid beta as demonstrated in the trials.
Prof. Mori shares his idea one step ahead.
“Microcirculation convey oxygen and nutrients to every part of human body, while helping excretion by gathering waste products.
Aduhelm might remove amyloid beta, but how is it gathered and where does it go?
It’s about ameliorating microcirculation that regulates overall physiological functions for improve cognitive functions.”
Prof. Mori’s insight is showing a way to true improvement of cognitive functions.
KOUKA is a processed food patented as a composition of matter to ameliorate cognitive dysfunctions, containing edible linseed oil, extract essence from Ganoderma lucidum, beer yeast (containing selenium), mackerel peptide DHA, EPA and fungus carbon powder.
We are sure that KOUKA would free modern society from threats of aged population and dementia.
We will never stop going for the goal.
〇 Introduction of Matrix
Contains 50/100mg of coenzyme Q10 per capsule essential for your health and beauty.
4 main features of Matrix
1. The world’s first mixture of the coenzyme and peanut oil
2. The Japan’s first food to contain 50/100mg of ubiquinone per capsule
3. Great safety of bio-fermented ubiquinone
4. The world’s first food to utilize new soft capsule
■ CoQ10 is a coenzyme that exists in every cell of human body.
It is essential for your body to generate energy.
A human body (60kg) has 700 mg of CoQ10.
The amount is decreased with age and making up the loss only with meals is difficult, so a good option is to benefit from a high quality supplement.
CoQ10 provides antioxidant action to keep your cells young and fresh.
It is the only antioxidant that can penetrate into mitochondria.
CoQ10 exists especially in the heart, lever, lungs and kidneys with the amount that decreases with age.
One of the two essential function of CoQ10 is the ignition to promote energy generation.
The efficiency of our energy generation system is known to be lower without the substance.
The other is antioxidant action, which protects cells from active oxygen and keep the body young and fresh.
CoQ10 is the only antioxidant that can penetrate into mitochondria.
Trade Name: Matrix 50
Name: Processed food of coenzyme Q10
Ingredients: Peanut oil, Coenzyme Q10, Beeswax, (Encapsulant) Gelatin, Glycerin, Caramel
Content:
[Large bottle] 192g (320mg × 600 capsules), 100,000JPY
[Box] 4 capsules × 30 packets, 22,000JPY
[Small bottle] 9.6g (320mg × 30 capsules), 5,800JPY
– Contains 50mg of CoQ10 per capsule
– Excellent safety by the bio-fermentation method
– Increased absorption by newly developed soft capsule
– Patent-pending blending process with peanut oil
– Higher absorption of CoQ10 than VE or rice germ oil
Trade Name: Matrix 100
Boosts combustion efficiency of your body
Content: 16.7g (525mg × 30 capsules), 9,800JPY
– Contains 100mg of CoQ10 per capsule
– Excellent safety by the bio-fermentation method
– Increased absorption by newly developed soft capsule
– More efficiency by 100mg of CoQ10 per capsule
Higher absorption of CoQ10 than VE or rice germ oil achieved by a newly developed blending process with peanut oil
Ubiquinone is known as coenzyme Q10.
It is also called vitamin Q, because it acts like a vitamin in human body.
This crucial material for generating energy is produced in lever, and decreased with age or unbalanced diet.
Being sensitive to heat or direct sunlight, ubiquinone is prone to shortage in modern diet with lots of processed food.
The organ that needs it the most is the heart, followed by the lever, adrenal gland, kidneys, testicles, ovaries and muscles.
Ubiquinone is used as medicine to enhance myocardial metabolism in Japan, while used for following diseases in the world because it promotes ATP generation in entire body:
1. Heart diseases
2. Lever diseases
3. Immunity deficiencies
4. Neoplasm (adjuvant treatment of tumor)
5. Chronic fatigue syndrome
6. Muscular dystrophy
7. Prevention of drug side effects
8. Periodontal diseases
9. Other diseases.
Ubiquinone is contained in supplements commonly used in the US and Europe for a variety of purposes, such as diet (by metabolic activation), muscle building (by energy replenishment), beauty (by antioxidant action), aging prevention, revitalization and cancer prevention.
It has gathered attention as the members of the British Olympic team took it.
◎ The history of study on ubiquinone
1957 Prof. Frederick Crane and his team in the University of Wisconsin succeeded to isolate an orange-yellow crystal from mitochondria of bovine myocardium and named it “CoQ10”.
1950’s R. A. Morton et al. of the University of Liverpool found a new quinone compound in the liver of vitamin A-deficient rats and named it “ubiquinone”. Later on, CoQ10 and ubiquinone were found to be the same.
1974 CoQ10 was approved as a “myocardial metabolism improving drug” in Japan.
2001 CoQ10 was approved to be sold as “food”.
〇 Latest news on dementia and its prevention
– Artificial intelligence accurately predicts who will develop dementia in two years
Artificial intelligence can predict which people who attend memory clinics will develop dementia within two years with 92 per cent accuracy, a largescale new study has concluded. Using data from more than 15,300 patients in the US, researchers found that a form of artificial intelligence called machine learning can accurately tell who will go on to develop dementia.
https://www.sciencedaily.com/releases/2021/12/211216145926.htm
– Researchers identify sildenafil as candidate drug for Alzheimer’s disease
A new study has identified sildenafil — an FDA-approved therapy for erectile dysfunction (Viagra) and pulmonary hypertension (Ravatio) — as a promising drug candidate to help prevent and treat Alzheimer’s disease. Researchers determined that sildenafil is associated with 69% reduced incidence of Alzheimer’s.
https://www.sciencedaily.com/releases/2021/12/211206113001.htm
– How meditation can help you make fewer mistakes
Meditating just once proves to make a difference
If you are forgetful or make mistakes when in a hurry, a new study from Michigan State University — the largest of its kind to-date — found that meditation could help you to become less error prone.
https://www.sciencedaily.com/releases/2019/11/191111124637.htm
〇 100 things by Dr. Hasegawa, the developer of HDS-R
This is the last installment of a series of articles to introduce what Dr. Hasegawa found.
At home and abroad, Dr. Kazuo Hasegawa enormously contributed to establishment of the groundwork for diagnosis of dementia.
Dr. Hasegawa dedicated his life as a psychiatrist, holding various positions including a director emeritus in the Center for Dementia Care Study and Training in Tokyo.
Unfortunately, on November 13, he died of old age at 92.
The funeral was held by relatives.
Back in 2017, at the age of 88, he disclosed his disease.
He had argyrophilic grain dementia.
After spending many years studying dementia, Dr. Hasegawa became one of those living with dementia.
He decided to make it public, because he wanted to let people know that anybody can have dementia.
And also, he wanted to make society more open to the disease.
Hoping to make it easier for those living with dementia to talk about the disease openly, he published a book titled I’m Enjoying my Spiritual Life with Dementia.
In the book Dr. Hasegawa shares 100 things he found.
91. 65 is still young. That recognition will be more common in the future.
92. People can live almost for a hundred years today. More than half of those who are 90 or older have dementia.
93. Japan needs to take immediate anti-dementia action, in addition to countermeasure against the aging population and declining rate of birth.
94. I think dementia medical care is to give thought to the journey of life together with a person with the disease and his/her family to support them, from the first medical examination to the last of that person’s life.
95. Dr, Hayao Kawai (psychologist, EdD, died in 2007) said “patients bring their episodes to hospitals only to get disease names” to describe the situation of dementia medical care. I was really ashamed to hear these words.
96. It is important for doctors and caregiving professionals to avoid instant denial to what a family member does for a person with dementia, even if the approach raises some questions.
97. Medical and caregiving professionals need to behave as “2.5th person”, sometimes getting very close to a patient’s heart, other times keep a distance from a patient or his/her family to respect medical perspectives.
98. A dementia-friendly town must be easy place to live for anyone.
99. Each of us can build new bonds to support all the people including those with dementia. We need the effort to realize such society.
100. If we can spread the light of affection and kindness to others, this world will be enfolded by a glow of hope.
Prof. Masao Mori, who is a friend of Dr. Hasegawa’s son’s, had a plan to have a collaborative action with Dr. Hasegawa on improvement of cognitive functions.
It is very regrettable that the plan will never become reality.
We offer our sincere prayers for the repose of Dr. Hasegawa’s soul.
〇 What is KOUKA?
KOUKA is a processed food of Ganoderma lucidum. The ingredients are edible linseed oil, extract essence from Ganoderma lucidum, beer yeast (containing selenium), mackerel peptide DHA, EPA, fungus carbon powder (enzymatic decomposition product), dextrin (encapsulant), gelatin, glycerin, glycerol ester of fatty acid, and pullulan.
KOUKA is chemical free food. It is designed to deliver reishi essence and other substances that positively effect on cognitive functions to the brain through the blood-brain barrier. By improving microcirculation, it enhances oxygen and nutrition supply to the brain, as well as excretion of waste products from the brain.
Aduhelm might be able to remove brain plaques, but they might not be excreted.
KOUKA has a physiological function to carry waste out of the brain.
〇 International mail delivery of KOUKA
Every overseas order for one package costs the total amount of 42,000JPY including the product’s price (39,000JPY) and EMS charge (3,000JPY).
We accept PayPal payment.
Don’t forget to check on the custom duty for your country before ordering.
Please be advised that the custom duty, if any, will be charged to the recipient.
https://dis-shop.info/product/kouka/
Thank you very much for your understanding and support to our activities.
We greatly appreciate medical professionals in the world for their dedicated work against the treats of COVID19.
Our association aims to bring more smiles in families, by supporting cognitive function’s recovery.
For the recovery, normalizing microcirculation is highly efficacious.
We found dosing proper amount of reishi, a gift of nature, is essential for better microcirculation.
KOUKA is a processed food product of Ganoderma Lucidum (reishi), patented in Japan as a composition of matter to ameliorate cognitive dysfunctions.
Almost 100% of KOUKA users who took it for 3 months experienced alleviation of cognitive dysfunctions and life style diseases.
We strongly believe cognitive functions can be recovered and there is no need to give up even after the onset of dementia.
With this conviction, our association has conducted physiological studies for more understanding of the nature of human body, as well as offering a wide range of awareness campaigns.
We are always open to share what we found with many people as possible.
We deliver further information at the official website.
DISAJP distributes valuable information on the 4th of each month to the world.
We welcome your feedback.
You can purchase the high quality reishi supplement KOUKA efficacious for improving cognitive functions at DIS SHOP.