New Drug, New hope.
On January 6th, FDA released a statement affirming their approval of a drug called Lecanemab for the treatment of Alzheimer’s disease. Through an accelerated method, this drug was approved as medication for patients with this brain disease as the disease currently has no definitive treatment options.
What is Alzheimer’s disease?
Alzheimer’s disease was discovered by Alois Alzheimer. It is a brain disease that starts with mild memory loss. It eventually progresses with symptoms of confusion, severe forgetfulness, lack of coordination followed by dementia-related symptoms such as complete lack of response to the environment, behavioral changes, severe deterioration of motor skills and finally secondary infections and organ failures.
Why does it happen? – The Biology
Two proteins called Tau and Amyloid are key drivers in Alzheimer’s disease. There is an abnormal build up of these proteins within the brain which becomes sticky deposits called “Plaques”. These accumulate over time to disrupt the functioning of the brain by blocking out communication and signals within the brain cells. We do not know how this initiates in the brain. Over a period of time, the brain itself starts to shrink and deteriorate. Parts of the brain responsible for memory is usually the first areas that are affected. These plaques are very sticky and difficult to surgically remove as damage to the brain is almost certain if one was to try. The approach that scientists have taken is to find and use a drug that must slowly “digest” and degrade only the plaque thus leaving the brain unaffected. And this is where the challenge lies.
Why do we need a new drug?
As of date, there exists very minimal number of drugs used in the treatment of this disease. Aducanumab, is a drug made by Biogen (an American MNC) that was approved on June 07, 2021, almost 20 years after the last approval of a drug for Alzheimer’s disease! With a lot of controversies related to its use (such as brain swelling and bleeding in some cases), there is a constant search for more effective treatment options with minimal side effects. Moreover, it is not a one-step treatment for the disease which makes patients’ lives difficult as insurers do not approve claims related to this very expensive drug. Finally, some researchers and medical professions also question the effectiveness of this drug. They do not believe it should be prescribed. All in all, this drug was a flop in the market, making very less in sales and profits.
How is the new drug better?
The main problem with Aducanumab (sold under the name “Aduhelm”) is its extremely high cost of 56,000 USD (approx 50 Lakh rupees) and lack of clear effectiveness. Lecanemab (marketed as LEQEMBI) is a drug that is developed by Eisai, a Japanese company (partnered with Biogen). Research shows that it binds more effectively to these plaques and allows for better clearance of these proteins from the brain compared to the previous drugs. Moreover, Eisai states that the launch price of this drug would be 26,000 USD as they want it to be more affordable to the society and those who need it.
So it is ACTUALLY better?
Research-wise, YES. It definitely shows more effective results in experiments. The FDA decision was based on phase II results which shows the effective decrease in plaques of 856 patient brains. Phase III, a more recent result, shows that the double-blinded clinical studies have a success rate of 27% in a sample group of almost 1800 patients. One significant point is that the previous drug Aducanumab seemed to have had worse side effects. Lecanemab usage is termed “less serious or fatal” although medical supervision is required post administration. In practice, it is too soon to say.
Controversy and gossip.
Honestly, I am always skeptical of accelerated approval of drugs as they do not allow for the deep investigation of these drugs in the overall well being of the patient. Here is an excellent way of understanding the importance of this, taken from an article on Nature
The controversy around aducanumab, which the FDA granted accelerated approval on 7 June 2021, has cast a shadow over lecanemab. Many researchers thought that aducanumab, which also goes by the brand name Aduhelm, did not show a strong signal of cognitive decline. The FDA’s own scientific advisory panel recommended against approving the antibody in an 8–1 vote, and three panel members resigned after the FDA authorized it anyway. The FDA did not hold a public advisory meeting for lecanemab before approving it.
And here is what the director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, Billy Dunn, has to say:
“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones. This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease.”
The Take-Away point
Here is a drug that is “more-affordable”. It is used in patients with initial stage of AD showing mild cognitive disturbances. Research shows that it has a 27% success rate. It is the best shot as of now in drug development space of Alzheimer’s disease.