Recently CNN.co.jp reported the following:
アルツハイマー新薬、臨床試験で進行抑える効果 安全性に懸念も
2022.12.01 Thu posted at 14:31 JST
（ＣＮＮ） 米バイオジェンと日本のエーザイが開発しているアルツハイマー病治療薬「レカネマブ」の臨床試験で、認知機能の低下を抑える効果がみられたことを示すデータが発表された。一方で安全性への懸念も浮上している。
これに先立つ第２相試験では、レカネマブを１年間投与したグループとプラセボ（偽薬）のグループの間に意味のある差はみられなかった。
米アルツハイマー協会は２９日、第３相試験の詳細なデータに勇気づけられているとの声明を発表。レカネマブによって患者が日常生活に参加し、自立した暮らしを続けられる期間は延びることが示されたと述べた。
第３相試験は北米、欧州、アジアの計２３５カ所で、２０１９年３月から２１年３月までの間、アルツハイマー病初期の軽度認知障害（ＭＣＩ）などが認められる５０～９０歳の成人１９７５人を対象に実施された。
参加者のうち無作為に選んだ約半数には、２週間ごとに点滴でレカネマブが投与され、残りの半数には偽薬が与えられた。
試験を開始した時点で、臨床的認知症尺度（ＣＤＲ―ＳＢ）のスコアは両グループとも約３．２だった。このスコアが１年半後、偽薬のグループで１．６６ポイント上昇したのに対し、レカネマブを投与したグループは１．２１ポイントの上昇にとどまった。
研究チームのメンバーが２９日、米サンフランシスコでの学会で報告したところによると、グループ間の差は半年後の時点から目立っていた。
レカネマブは、アルツハイマー病患者の脳内に蓄積されるたんぱく質「アミロイド・ベータ」と結合し、これを取り除くことによって効果を発揮する。
試験開始時に患者の脳内にたまっていたアミロイド・ベータの量の平均は、レカネマブ組が７７．９２センチロイド、プラセボ組が７５．０３センチロイドだった。
これに対して１年半後の平均は、レカネマブ組が５５．４８センチロイドも減少したのに対し、プラセボ組は３．６４センチロイド増えていた。
期間中の有害事象で試験を中止した参加者の割合は、レカネマブ組が６．９％、プラセボ組が２．９％だった。
全体としてはレカネマブ組の１４％、プラセボ組の１１．３％で重大な有害事象が報告された。レカネマブ組で多かったのは点滴への反応と、脳浮腫や微小出血などのアミロイド関連画像異常（ＡＲＩＡ）。いずれも数カ月で回復した。
ＡＲＩＡのうち、出血はレカネマブ組の１７．３％に対してプラセボ組の１２．６％、脳浮腫はレカネマブ組の１２．６％に対してプラセボ組の１．７％にみられた。
ＡＲＩＡは、アポリポたんぱく質（ＡＰＯ）Ｅ４という遺伝子を持つ患者で多く発生していた。ＡＰＯＥ４はアルツハイマー病をはじめとする認知症自体の危険因子でもある。
死亡した参加者はレカネマブ組で６人、プラセボ組で７人。参加者全体に占める割合はそれぞれ０．７％、０．８％で、レカネマブの投与やＡＲＩＡとは無関係と考えられる。
研究チームは、初期のアルツハイマー病に対するレカネマブの有効性と安全性を検証するために、より長期にわたる試験が必要だと結論付けている。
米食品医薬品局（ＦＤＡ）には来年３月までに承認申請することを目指す。
エーザイによると、ＦＤＡは今年７月、迅速承認制度に基づくレカネマブのライセンス申請を受理した。迅速承認を認めるかどうかの判断は来年１月６日までに下される見通し。今後の検証試験で臨床的に有益だと確認されれば本承認となるが、そうでない場合は回収の指示が出る可能性もある。
Translation
(CNN) Regarding clinical trials of the Alzheimer's drug Lecanemab developed by US-based Biogen and Japan's Eisai, data released shown that it could slow down cognitive decline. At the same time, concerns about safety also emerged.
On November 29, Biogen and Eisai announced in the New England Journal of Medicine data on the final stage of Phase 3 clinical trials of an antibody drug Lecanemab. About two months ago, the two companies announced that a Phase 3 trial had confirmed the effect of suppressing cognitive decline by 27%.
An earlier phase II trial found no meaningful difference between the group using Lecanemab and the using placebo group in a one year trial.
The Alzheimer's Association of America issued a statement on Monday saying it was encouraged by the detailed data from the Phase 3 trial. It was said that Lecanemab showed to increase the length of time that patients were able to participate in daily life and remained independent.
Phase 3 trials were conducted at 235 locations in North America, Europe and Asia between March 2019 and March 2021 on adults aged 50 to 90 with mild cognitive impairment (MCI) in the early stages of Alzheimer's disease.
Approximately half of the participants were randomly selected to receive Lecanemab by infusion every two weeks, and the other half received a placebo.
At the start of the study, clinical dementia scale (CDR-SB) scores were approximately 3.2 in both groups. After a year and a half, the score increased by 1.66 points in the placebo group, compared with only 1.21 points in the Lecanemab group.
Members of the research team reported at an academic conference in San Francisco on the 29th that the difference between the groups was noticeable even after half a year.
Lecanemab worked by binding itself to amyloid-beta, a
protein that accumulated in the brains of Alzheimer's disease patients, and
after binding they were removed.
The mean amount of amyloid-beta accumulated in the brains of patients at the start of the study was 77.92 centroids in the Lecanemab group and 75.03 centroids in the placebo group.
In contrast, after 18 months, the Lecanemab group had a mean reduction of 55.48 centroids, while the placebo group had an increase of 3.64 centroids.
The percentage of participants who discontinued the trial due to adverse events during period was 6.9% in the Lecanemab group and 2.9% in the placebo group.
Overall, 14% of Lecanemab groups and 11.3% of placebo groups reported serious adverse events. In the Lecanemab group, reactions to infusion and amyloid-related imaging abnormalities (ARIA) such as cerebral edema and microhemorrhage were common. Both could recover within a few months.
Among ARIAs, hemorrhage occurred in 17.3% of Lecanemab versus 12.6% of placebo groups, and cerebral edema occurred in 12.6% of Lecanemab versus 1.7% of placebo groups.
ARIA occurred more frequently in patients carrying the gene apolipoprotein (APO) E4. APOE4 was also a risk factor for dementia itself including Alzheimer's disease as an example.
Six participants in the lecanemab group and seven in the placebo group died. The percentages of all participants were 0.7% and 0.8% respectively, and were considered unrelated to the administration of Lecanemab and ARIA.
The researchers concluded that longer-term trials were needed to test the efficacy and safety of Lecanemab in early Alzheimer's disease.
The company aimed to submit an application for approval to the US Food and Drug Administration (FDA) by March next year.
According to Eisai, the FDA accepted a license application for Lecanemab under the accelerated approval system in July this year. A decision on whether to approve accelerated approval was expected to be made by January 6 next year. If it could be confirmed that there could be clinically beneficial in future verification tests, it might be officially approved; but if it is not, it might be instructed to withdraw.
So, clinical trials of the
Alzheimer's drug Lecanemab show that it has the ability to slow cognitive
decline. At the same time, concerns about safety have also emerged. A decision
on approval is expected to be made by January 6 next year in the US. Many
people are looking forward to know the fate of Lecanemab.
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