It’s an­other step in the phar­ma­ceu­ti­cal in­dus­try’s long game in grow­ing its mar­ket by wid­en­ing the di­ag­nos­tic net to pull in lots of per­fectly nor­mal folks. Mak­ing peo­ple wor­ried that they’re sick when they’re prob­a­bly not is an ef­fec­tive busi­ness strat­egy for sell­ing the drug that may cure the dis­ease they prob­a­bly don’t have.

In this case, it’s the Alz­hei­mer’s mar­ket. Eli Lilly aims to cre­ate a sense of ur­gency for Ki­s­unla (also known as donan­e­mab), its new anti-amy­loid treat­ment for early Alz­hei­mer’s dis­ease. But while early treat­ment of, say, di­a­be­tes, can avoid long-term health risks, “early” treat­ment of Alz­hei­mer’s dis­ease with the class of drugs that in­cludes Ki­s­unla can only hurt peo­ple.

Un­proven hy­poth­e­sis

When Lilly first de­vel­oped anti-amy­loid drugs de­cades ago, the com­pany pro­moted the idea that amy­loid (sticky plaque in older brains) was the “bad guy” in Alz­hei­mer’s dis­ease. That un­proven hy­poth­e­sis took hold.

In fact, there is no ev­i­dence that amy­loid plaque in the brain is as­so­ci­ated with cog­ni­tive func­tion or that re­mov­ing it will im­prove clin­i­cal out­comes. One in three cog­ni­tively nor­mal el­ders over 70 have amy­loid plaque; by age 95 over half do. Most amy­loid car­ri­ers will never de­velop de­men­tia.

Ne­ver­the­less, Lilly’s cur­rent mar­ket­ing mes­sage is that there’s no time to wait to re­move amy­loid plaques from brains. “Time is Hid­ing Some­thing,” an un­branded web­site tar­get­ing health care pro­vid­ers, en­cour­ages early di­ag­no­sis of Alz­hei­mer’s dis­ease through the use of blood tests and PET scans that iden­tify amy­loid. Lilly is pitch­ing the same mes­sage to the pub­lic.

Olym­pic view­ers saw ads fea­tur­ing a Par­a­lym­pian warn­ing of the signs of early symp­tom­atic Alz­hei­mer’s dis­ease and en­cour­ag­ing them to visit “More Than Nor­mal Aging.”

The web­site raises con­cerns about mem­ory is­sues such as mis­placed keys and en­cour­ages a trip to the doc­tor for any­one ex­pe­ri­enc­ing symp­toms that are re­ally as­so­ci­ated with nor­mal aging. Con­ve­niently, Lilly of­fers a se­ries of ques­tions to ask the doc­tor, with half of them fo­cused on amy­loid.

Phar­ma­ceu­ti­cal com­pa­nies can make money off the tests, too: Lilly makes Amyvid and Tau­vid im­ag­ing agents for PET scans, and is de­vel­op­ing a blood test with Roche.

As soon as Ki­s­unla was ap­proved, branded web­sites ap­peared. The pre­scriber site pro­motes the drug with a mar­ket­ing-friendly pre­sen­ta­tion of clin­i­cal data and, for those who pre­fer video, reg­is­tra­tion for talks by Lilly-funded phy­si­cians.

A head­line boasts, “Ki­s­unla gives you the power to help slow cog­ni­tive and func­tional de­cline in pa­tients with early symp­tom­atic AD.” In fact, while the rate of cog­ni­tive de­cline in the group treated with donan­e­mab was statis­ti­cally less than pla­cebo, the dif­fer­ence was not clin­i­cally mean­ing­ful and would not be enough for a pa­tient or fam­ily mem­ber to no­tice.

Lilly’s plan

The branded con­sumer web­site warns of the con­se­quences of amy­loid plaque, as­so­ci­at­ing amy­loid build up with dif­fi­culty re­mem­ber­ing ap­point­ments, find­ing the right names, or re­tain­ing new in­for­ma­tion — all is­sues that can cer­tainly be as­so­ci­ated with nor­mal aging.

If all goes ac­cord­ing to Lilly’s plan, peo­ple with com­pletely nor­mal cog­ni­tion will be el­i­gi­ble for donan­e­mab. The mere pres­ence of amy­loid plaques in cog­ni­tively nor­mal peo­ple will be suf­fi­cient to di­ag­nose Alz­hei­mer’s dis­ease.

Donan­e­mab does re­move amy­loid plaque, and as long as peo­ple think that clear­ing amy­loid plaque im­proves cog­ni­tion, that’s all Lilly needs for a mar­ket­ing mes­sage. If these drugs were harm­less, these cam­paigns would be less im­por­tant, but donan­e­mab comes with se­ri­ous risks.

Three donan­e­mab-treated clin­i­cal trial par­tic­i­pants died from brain bleed­ing or swell­ing, an ad­verse ef­fect ex­pe­ri­enced by more than one in three par­tic­i­pants in the clin­i­cal tri­als. Even when these brain in­ju­ries were asymp­tom­atic, mod­er­ate or se­vere cases re­quire stop­ping donan­e­mab un­til the bleed or swell­ing re­solves.

Will pa­tients on these drugs get the reg­u­lar MRIs that were done in the trial to de­tect bleed­ing or swell­ing be­fore it’s too late? Donan­e­mab treated par­tic­i­pants also showed an ac­cel­er­at­ing rate of brain shrink­age in com­par­i­son to pla­cebo. Re­duc­tion in brain vol­ume can be ex­pected to worsen cog­ni­tion over time.

Those with a gene linked to Alz­hei­mer’s dis­ease, ApoE ε4, are at much greater risk for brain bleed­ing and swell­ing. Ac­cord­ing to the la­bel, “test­ing for ApoE ε4 sta­tus should be per­formed prior to ini­ti­a­tion of treat­ment” to de­ter­mine risk of brain bleed­ing and swell­ing. How­ever, the la­bel con­tin­ues on to ex­plain that there are no FDA-au­tho­rized tests for this sta­tus, so this in­for­ma­tion is use­less.

Wrong ap­proval

The FDA should not have ap­proved donan­e­mab. The Euro­pean Med­i­cines Agency re­cently re­jected le­can­e­mab, an­other anti-amy­loid drug ap­proved in the U.S. with a sim­i­lar risk-ben­e­fit pro­file as donan­e­mab, be­cause the safety con­cerns of brain bleed­ing and swell­ing out­weighed the small im­pact on slow­ing of cog­ni­tive de­cline. Donan­e­mab is cur­rently be­ing con­sid­ered by EMA.

An­drew Lech­leiter, Lilly’s vice pres­i­dent of Alz­hei­mer’s dis­ease mar­ket­ing, de­scribes a mar­ket­ing push with a goal to “light a fire at the ear­li­est stages in pri­mary care.” Now’s the time to douse that fire and pro­tect el­ders from the risks of anti-amy­loid treat­ments.

Judy Butler is a research fellow at PharmedOut. Adriane Fugh-Berman is professor at the Georgetown University Medical Center, where she also directs PharmedOut.

First Published: August 20, 2024, 9:30 a.m.