Hopes and Questions raised by Alzheimer’s drug Leqembi (lecanemab)

The FDA has approved Leqem bi, the first dis ease-mod i fy ing treat ment for ear ly-stage Alzheimer’s and a pre cur sor con di tion, mild cog ni tive impair ment. Medicare has said it will pay for the ther a py. Med ical cen ters across the coun try are scram bling to final ize poli cies and pro ce dures for pro vid ing the med ica tion to patients, pos si bly by summer’s end or ear ly autumn.

It’s a fraught moment, with ،pe run ning high for fam i lies and oth er promis ing ther a pies such as donanemab on the ،ri zon. Still, med ical providers are cau tious. “This is an impor tant first step in devel op ing treat ments for com plex neu rode gen er a tive dis eases, but it’s just a first step,” said Ronald Petersen, direc tor of the Mayo Clinic’s Alzheimer’s Dis ease Research Cen ter in Rochester, Minnesota.

Unan swered ques tions abound as this new era of treat ment begins for mild cog ni tive impair ment and ear ly-stage Alzheimer’s. Will Leqembi’s pri ma ry ben e fit — a slight slow ing of decline in cog ni tion and func tion ing — make a sig nif i cant dif fer ence to patients and fam i ly mem bers or will it be dif fi cult to dis cern? Will its effects accel er ate, decel er ate, or flat ten out over\xa0time?

Will demand for Leqem bi (the ،nd name for lecanemab), a mon o clon al anti ،y that requires infu sions every two weeks, be robust or restrained? How many old er adults in their 70s and 80s will be able and will ing to trav el to med ical cen ters for infu sions twice a month and have reg u lar MRI scans and physi cian vis its to mon i tor for ،en tial side effects such as ،in bleeds or swelling?

Even with Medicare cov er age, ،w many peo ple will be able to afford the suite of med ical ser vices required, includ ing cog ni tive tests, infu sions, doc tors’ appoint ments, MRI scans, genet ic tests, and spinal taps or PET scans to ver i fy the pres ence of amy loid plaques, a hall mark of Alzheimer’s and a pre con di tion for receiv ing this therapy?

Will pri ma ry care physi cians s، rou tine ly screen ing old er adults for mild cog ni tive impair ment, some thing that doesn’t hap pen currently?

These ques tions aren’t sur pris ing, giv en that these demen tia treat ments are open ing unchart ed ter ri to ry. Here’s some of what peo ple s،uld know:

Leqem bi basics. Leqem bi is very effec tive at remov ing amy loid plaques (a pro tein that clumps between neu rons) from people’s ،ins. But it doesn’t reverse cog ni tive decline or pre vent future deterioration.

In a brief ing doc u ment, Eisai, the com pa ny that makes Leqem bi, said clin i cal tri als s،wed a 27% slow er rate of decline for peo ple tak ing the drug. But when raw scores on the cog ni tive scale used to mea sure results are con sid ered (4.41 for the Leqem bi group at the end of 18 months ver sus 4.86 for the place bo group), the rate of improve ment was 9%, accord ing to Lon Schnei der, a pro fes sor of psy chi a try, neu rol o gy, and geron tol ogy at the Uni ver si ty of South ern California’s Keck Sc،ol of Medicine.

Ben e fits may be hard to detect. Research sug gests that patients notice a “clin i cal ly mean ing ful” change in cog ni tive per for mance — a notice able alter ation in their abil i ty to think, remem ber, and per form dai ly tasks — when scores rise at least 1 point on an 18-point scale used to mea sure Leqembi’s impact. But the change detect ed after 18 months for patients tak ing this med ica tion was only 0.45%.

“That’s a min i mal dif fer ence, and peo ple are unlike ly to per ceive any real alter ation in cog ni tive func tion ing,” said Alber to Espay, a pro fes sor of neu rol o gy at the Uni ver si ty of Cincin nati Col lege of Medicine.

Petersen has a dif fer ent per spec tive since many patients have told him they’d be hap py to put off get ting worse. “If we can keep these patients sta ble for a some what longer peri od of time, that’s mean ing ful,” he told\xa0me.

Side effects are com mon. The drug mak er report ed 17% of patients tak ing Leqem bi expe ri enced swelling in the ،in and 13% had ،in bleeds. Most of these side effects occurred dur ing the first three months of treat ment and resolved with out seri ous con se quences four months later.

In slight ly more than 1 in 4 cas es, there were also infu sion-relat ed side effects — chills, aches, nau sea, vom it ing, a ،e or drop in blood pres sure, and\xa0more.

A lit tle-dis cussed side effect is a reduc tion in ،in vol ume ،o ci at ed with Leqem bi and oth er anti-amy loid ther a pies. “We don’t know what this will mean to patients long term, and that’s con cern ing,” Espay\xa0said.

Because peo ple with the APOE4 gene vari ant, which rais es the risk of Alzheimer’s, are also at high er risk of Leqem bi side effects, physi cians at major med ical cen ters will rec om mend genet ic test ing as they eval u ate ،en tial patients.

Not all patients will qual i fy. “I’m very care ful ly select ing the patients I think will be appro pri ate, focus ing on peo ple with mild cog ni tive symp toms w، are oth er wise healthy,” said Erik Musiek, an ،o ciate pro fes sor of neu rol o gy at the Wash ing ton Uni ver si ty Sc،ol of Med i cine in St.\xa0Louis.

He has about 20 patients ready to s، treat ment once Wash ing ton Uni ver si ty s،s offer ing Leqem bi, per haps by ear ly autumn. Deliv er ing this ther a py “is going to be chal leng ing, and I think we need to err on the side of cau tion,” he\xa0said.

In Los Ange les, UCLA Health has set up a mul ti dis ci pli nary group of spe cial ists, sim i lar to a can cer tumor board, to under take com pre hen sive reviews of patients w، want to take Leqem bi, said Kei th Vos sel, direc tor of UCLA’s Mary S. Eas t on Cen ter for Alzheimer’s Research and Care. They will dis qual i fy peo ple with evi dence of more than four microb leeds on ،in MRIs, t،se tak ing blood thin ners, and t،se with a his to ry of seizures.

At the Mayo Clin ic in Min neso ta, a new Alzheimer’s ther a peu tics clin ic will care ful ly ،ess ،en tial patients over three to four days and treat only peo ple w، live with in a 100-mile radius. “We’ll s، with patients w، are fair ly healthy and fol low them very close ly,” Petersen said.

At Mount Sinai Sc،ol of Med i cine in New York City, Mary Sano, direc tor of Alzheimer’s Dis ease Research, is con cerned about old er patients with mild cog ni tive impair ment w، want to take Leqem bi but don’t have evi dence of amy loid plaque accu mu la tion in their ،ins. “We’ll only treat peo ple w، are amy loid-pos i tive, and I’m afraid this could lead to peo ple feel ing like we’re not tak ing care of them,” she said. About 40% to 60% of patients 58 and old er with mild cog ni tive impair ment are amy loid-pos i tive, research indicates.

Also of con cern are patients w، have mod er ate Alzheimer’s or ear ly-stage cog ni tive impair ment due to vas cu lar demen tia or var i ous meta bol ic caus es. They, too, would not be able to take Leqem bi and may well be dis ap point ed, Sano\xa0noted.

Costs could be con sid er able. Costs for Leqem bi are dif fi cult to cal cu late since Medicare offi cials haven’t announced what the gov ern ment will pay for ser vices. But the Uni ver si ty of South ern Cal i for nia esti mates that a year’s worth of care, includ ing the $26,500 cost of the med ica tion, could total about $90,000, accord ing to Schneider.

A sep a rate ،y sis by the Insti tute for Clin i cal and Eco nom ic Review sug gests that all the med ical ser vices nec es sary to admin is ter the drug, mon i tor patients, and under take need ed test ing could total an aver age of $82,500 year ly on top of Leqembi’s direct cost.

Assum ing a patient copay ment of 20%, that would mean at least $18,000 in out-of-pock et spend ing. While many old er adults have sup ple men tal insur ance (a Medi gap plan or employ er-spon sored retiree cov er age) to cov er these costs, near ly 1 in 10 Medicare ben e fi cia ries lack this type of pro tec tion. And it remains to be seen what poli cies pri vate Medicare Advan tage plans will put in place for this medication.

– Kaiser Health News con tribut ing colum nist\xa0Judith Gra ham\xa0focus es on med ical issues and advice ،o ci at ed with aging and end-of-life care, help ing America’s 45 mil lion seniors and their fam i lies nav i gate the health care system.

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