Ex­pert pan­el re­view on Alzheimer’s drug ad­u­canum­ab be­comes a one-day tri­al by fire as crit­ics turn their guns on Bio­gen — and the FDA

Two days af­ter an en­thu­si­as­tic FDA in­sid­er re­view of Bio­gen’s ad­u­canum­ab pro­vid­ed a $15 bil­lion pop for the big biotech’s mar­ket cap, a pan­el of out­side ex­perts pro­vid­ed some fresh fire­works on the de­bate, with a big ma­jor­i­ty turn­ing thumbs down on the con­tro­ver­sial pitch that there are da­ta to prove the drug is ef­fec­tive — as well as the agency’s per­plex­ing en­dorse­ment.

Most of the ex­perts slapped down 3 ques­tions re­gard­ing whether there was any ev­i­dence to back the ef­fi­ca­cy of the drug — with a lone vote in fa­vor on one of the ques­tions.

The mon­ey ques­tion:

Con­sid­er­ing all the tri­al da­ta, the FDA asked, is it rea­son­able to con­sid­er the pos­i­tive study 302 “as pri­ma­ry ev­i­dence of ef­fec­tive­ness” for the treat­ment of Alzheimer’s dis­ease?

Ten said no, none said yes and there was one ab­sten­tion. Sev­er­al said the FDA pre­sen­ta­tion was heav­i­ly weight­ed in Bio­gen’s fa­vor, with no dis­cus­sion from the agency of the harsh­ly crit­i­cal sta­tis­ti­cal re­view from FDA staffers.

Any­one ex­pect­ing a dry and dis­pas­sion­ate re­view of the da­ta for Bio­gen’s Alzheimer’s drug ad­u­canum­ab at the FDA pan­el meet­ing Fri­day was in for a rude awak­en­ing.

Bil­ly Dunn

Both Bio­gen ex­ecs as well as Bil­ly Dunn, the head of the agency’s neu­ro­sciences di­vi­sion, of­fered a full-throat­ed en­dorse­ment of the drug, out­lin­ing the rea­sons why they found the da­ta back­ing the con­tro­ver­sial ap­pli­ca­tion “com­pelling.”

That ar­gu­ment, though, in­vit­ed a sharp shove back from mem­bers of the ad­vi­so­ry pan­el asked to weigh in on the ap­pli­ca­tion, es­pe­cial­ly from the sta­tis­ti­cians who re­peat­ed­ly probed why Dunn was so sup­port­ive when the FDA’s sta­tis­ti­cal re­view took the com­plete­ly op­pos­ing view, con­clud­ing that the da­ta were con­flict­ing, of­fered clear ev­i­dence that the drug doesn’t work and that Bio­gen’s ar­gu­ment in its fa­vor was hol­low.

“We brought in­no­v­a­tive think­ing to this un­usu­al sit­u­a­tion,” ar­gued Dunn, con­struct­ing sup­port for ad­u­canum­ab that dis­count­ed the ear­ly ter­mi­na­tion of the study due to fu­til­i­ty, of­fer­ing rea­sons why the 1 pos­i­tive late-stage study of­fered “ex­treme­ly per­sua­sive” rea­sons for an ap­proval, why the oth­er failed study could be ex­plained as pro­vid­ing sup­port­ing da­ta and why a small co­hort in an ear­li­er study al­so pro­vid­ed en­cour­age­ment for an OK — es­pe­cial­ly as Covid-19 de­mand­ed reg­u­la­tors to work co­op­er­a­tive­ly in sal­vaging tri­als.

Sev­er­al mem­bers of the pan­el were clear­ly out­raged by that.

G. Caleb Alexan­der, a Johns Hop­kins pro­fes­sor, blast­ed the FDA’s re­view as “strik­ing­ly in­con­gru­ous” which of­fered con­clu­sions that were at best com­pelling­ly con­flict­ed, rais­ing ques­tions on how the FDA could de­ter­mine there was ev­i­dence of ef­fec­tive­ness.

“It just feels like the au­dio and the video on the TV are out of sync,” he said.

For every point that sug­gests sup­port for the drug, he added, there are more that raise con­cerns.

At sev­er­al points, Alexan­der harsh­ly crit­i­cized Dunn’s team for skew­ing the brief­ing doc­u­ments and ques­tions in Bio­gen’s fa­vor. “I’m call­ing out the fact … that this ques­tion is open to elic­it­ing se­lec­tive in­for­ma­tion,” he not­ed at one point.

The Uni­ver­si­ty of Wash­ing­ton’s Scott Emer­son was an­oth­er per­sis­tent crit­ic with point­ed crit­i­cism of the drug and the da­ta used to back the ap­pli­ca­tion.

And Joel Perl­mut­ter, a pro­fes­sor of neu­rol­o­gy, warned the pan­el that if the FDA ap­proved some­thing with­out strong ev­i­dence of ef­fi­ca­cy they would pre­vent a good and ef­fec­tive treat­ment from be­ing ap­proved “for more than a cou­ple of years, for many years.”

The friend­liest ques­tion the pan­el faced con­cerned whether tri­al 302, count­ed as the on­ly pos­i­tive study of the 2 Phase III ef­forts, pro­vid­ed strong ev­i­dence of ef­fi­ca­cy — if you al­so ig­nore 301, the failed tri­al.

That went down hard, with 8 ‘no’ votes, 1 ‘yes’ and 2 ab­sten­tions. Even the ab­stain­ers, though, of­fered ob­jec­tions.

How about the small­er study 103, the Phase II tri­al Dunn cit­ed for of­fer­ing some sup­port­ive da­ta for the drug? Was it sup­port­ive in some way?

The ex­perts shot that one down as well, by a vote of 7 no, 0 yes and 4 un­cer­tain.

The one up­beat re­sult was on patho­phys­i­ol­o­gy, but sev­er­al not­ed ques­tions whether the drug’s abil­i­ty to re­duce amy­loid would ever trans­late in­to ef­fi­ca­cy or an im­pact on symp­toms. That earned some sup­port: 5 yes and 6 un­cer­tain.

“I view the ques­tion nar­row­ly,” said Chia­di Onyike, say­ing there was clear ev­i­dence it mopped up amy­loid be­ta. And oth­ers not­ed ques­tions whether that was enough to gain clin­i­cal ef­fi­ca­cy, or if it’s the cor­rect bio­mark­er to use at all.

The FDA doesn’t have to con­sid­er the pan­el vote in mak­ing its de­ci­sion. In this case, giv­en the heat­ed ob­jec­tions, it would be hard to ig­nore. But giv­en Dunn’s ear­li­er de­ci­sions sup­port­ing Sarep­ta, there is still a dis­tinct pos­si­bil­i­ty of an ap­proval.

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Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

David Baker working with a student on their protein design (Jason Mast)

Sci­en­tists are fi­nal­ly learn­ing how to de­sign pro­teins from scratch. Drug de­vel­op­ment may nev­er be the same

SEATTLE — It’s a cloudy Thursday afternoon in mid-July and David Baker is reclining into the futon in his corner office at the University of Washington, arms splayed out like a daytime talk show host as he coaches another one of his postdocs through the slings and arrows of scientific celebrity.

“Be jealous of your time,” he says, before plotting ways of sneaking her out of Zooms. “It’s this horrible cost to science that you’re tied up in some stupid meeting.”

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Patty Murray, D-WA (Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­ate user fee reau­tho­riza­tion bill omits ac­cel­er­at­ed ap­proval re­forms, shows wide gaps with House ver­sion

The Senate health committee on Tuesday released its first version of the bill to reauthorize all the different FDA user fees. But unlike the House version, there are only a few controversial items in the Senate’s version, which does not address either accelerated approval reforms or clinical trial diversity (as the House did).

While it’s still relatively early in the process of finalizing this legislation (the ultimate statutory deadline is the end of September), the House and Senate, at least initially, appear to be starting off in different corners on what should be included.

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Pre­sent­ing a live End­points News event: Man­ag­ing a biotech in tur­bu­lent times

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

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The case in question from last October saw a US appeals court overturn a prior FDA court win, saying that the agency never should’ve approved a rare disease drug because a previously approved but more expensive drug with the same active ingredient has orphan drug exclusivity barring such an approval.

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Fast forward two years later, and bluebird has withdrawn Zynteglo, the beta thal drug, along with the rest of its gene therapy portfolio from Europe, which the company said is generally unwilling to pay a fair price for the treatment.

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A DC appeals court clerk and researchers from Harvard and the University of Calgary dug through all the patents and regulatory exclusivities granted to inhalers approved by the FDA between 1986 and 2020, finding that of the 62 inhalers approved, 53 (or 85%) were brand-name products, with a median of 16 years of protection from generic competition.

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Berk­shire Hath­away pulls out of Ab­b­Vie, Bris­tol My­ers Squibb in­vest­ments

It looks like Warren Buffett is sticking to ice cream and railroads for the moment.

The billionaire CEO of Berkshire Hathaway backed out of two major holdings in the pharma industry, Forexlive first reported, including a $410 million investment in AbbVie and a $324.4 million stake in Bristol Myers Squibb.

The move comes after Berkshire abandoned its Teva shares just last quarter, Bloomberg reported.

Long-ex­pect­ed UK lay­offs im­mi­nent for No­var­tis fol­low­ing sale

Nearly a year ago, more than 200 workers at Novartis’ Grimsby, UK, facility were able to hang on to their jobs after the pharma closed a Switzerland site as a part of its workforce restructuring plan. Now, it looks like those employees’ time is up, as the site has been sold, Grimsby Telegraph reported today.

The manufacturing site has been sold to Humber Industrials, a subsidiary of International Process Plants. None of the current staff members will be working with the new owners, however.