Biogen/Eisai AD new drug approval has high expectations, efficacy, safety, and payment price have attracted much attention!

The hallmark feature of AD is the deposition of β amyloid (Aβ) in the patient's brain, and the Aβ hypothesis (β amyloid overproduction and aggregation into amyloid plaques) is thought to be the initiation of the pathophysiology of AD
.

Leqembi is an anti-β amyloid (Aβ) antibody, which can bind to soluble and poorly soluble Aβ polymers, and promote their clearance, with the ability to change the pathology of the disease and alleviate the progression of the disease, so as to achieve the purpose
of treating Alzheimer's disease.

The FDA's accelerated approval is based on the results of a Phase IIb proof-of-concept clinical trial (BAN2401-G000-201), which included a total of 856 patients with mild cognitive impairment (MCI) and confirmed amyloid lesions
in patients with early-stage AD.

The trial results showed that Leqembi (10 mg/kg) once every two weeks reduced cerebral amyloid by 0.
306 SUVr (baseline mean 1.
37)
at 18 months of treatment.
With visual readings, more than 80% of subjects were negative
for amyloid.
And the degree of amyloid reduction is associated with
slower clinical decline in ADCOMS, CDR-SB, and ADAS-cog.
That is, amyloid in patients treated with Leqembi showed a dose- and time-dependent decrease, compared with amyloid levels in the placebo group
.

In addition, at the Alzheimer's Disease Clinical Trial Conference held at the end of 2022, Eisai/Biogen announced Clinical III As a result, Leqembi met the primary and secondary endpoints of the study and significantly slowed disease progression
in patients with early-stage Alzheimer's disease.

Phase III trial data showed that Leqembi treatment was at 18 compared to the placebo group Statistically significant differences
were shown at months.
It clinically showed lower cognitive and functional scale outcome data, and the subject's cognitive and functional decline was reduced 27% (a higher CDR-SB score means lower clinical function of the patient) and reduced amyloid deposition levels by approximately 70%
over 18 months.

And the condition of the Leqembi group was about the same as that of the placebo group at 18 months at 25.
5 months, which means that the drug slowed the progression of the disease by 7.
5 months
.

In this regard, the industry questioned that Leqembi is still based on the Aβ hypothesis, but the Aβ hypothesis itself still has a lot of unknowns, and the pathogenic mechanism of multiple other hypotheses has never been clear
.
Therefore, there is an opinion that Aβ-targeted antibodies act as AD There is great uncertainty
about the important direction of new drug development.
In addition, the significance of Leqembi's 27% improvement for Alzheimer's patients remains to be observed
in real-world clinical treatment.

In fact, the experts' wariness of Leqembi stems in large part from what happened
to Aduhelm.

June 2021, U.
S.
FDA Accelerated approval of Aduhelm despite little evidence that it actually slowed the development of AD, no committee members voted in favor, and experts raised concerns
about inconsistencies in clinical data on the drug.
In this regard, the FDA Several experts of the Expert Council publicly resigned in protest
.
Later that month, two congressional committees announced the launch of investigations into the FDA's decision to accelerate approval of
Aduhelm.

Late last year, the U.
S.
House Oversight and Reform Committee and the Energy and Commerce Committee released a 46-page staff report
after an 18-month investigation into the FDA's regulatory review and approval process for the Alzheimer's drug Aduhelm and Biogen's pricing of Aduhelm.

The report reveals the following information:

The FDA's interactions with Biogen were atypical and did not follow the agency's own documentation protocols
.

The FDA and Biogen did not cooperate properly
in a joint briefing document on a key advisory committee.

The FDA turned to using Aduhelm's accelerated approval pathway
on a vastly shorter timeline.

FDA approved, Biogen received a broad label indication for Aduhelm, and Biogen also had reservations despite the lack of clinical data for all stages of Alzheimer's disease
.

Biogen initially set an unreasonably high price tag of $56,000 a year for Aduhelm, "making history" for the company, despite the implications
for patients and health insurance plans.

Biogen expects Aduhelm to become a burden on health insurance, with high costs
for patients.

On the other hand, the excessively expensive price is also one of the
popular controversies.
According to Eisai, after considering and estimating many factors, Leqembi's price in the United States is $26,000 per year
.

John, Professor Emeritus of Neurosurgery at the University of California, San Francisco Dr.
Forsayeth is skeptical
.
Forsayeth said in an interview: "I don't think it's in the interest
of the health care system to spend that much money for a 27 percent improvement.
" ”

Aduhelm had been controversial for its overpriced $56,000 per year, even though Biogen cut Aduhelm's wholesale price in the U.
S.
in half in
December.

Market analysis, in June 2022, Eisai released an analysis that concluded that the cost-effectiveness of Leqembi is between $10,000 and $10,000 per year Between $35,000 seems to be paving
the way for this pricing.
However, the price of $26,000/year is still very expensive
.

Not long ago, the non-profit organization Institute for Clinical and Economic Evaluation (ICER) released a report that according to the clinical trial results that Leqembi has released so far, based on quantifiable value indicators for improving quality of life, the annual product price should be between
$8,500 and $20,600.

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