FDA and Bio­gen dis­cussed Aduhelm's ac­cel­er­at­ed ap­proval as ear­ly as 2019 — re­port

Top FDA neu­ro­science of­fi­cial Bil­ly Dunn has been a vo­cal ad­vo­cate for Bio­gen and its Alzheimer’s drug Aduhelm through­out the en­tire re­view process all the way up to the drug’s di­vi­sive ac­cel­er­at­ed ap­proval. That en­thu­si­asm — which had drawn the ire of ad­vo­ca­cy groups and the ad­comm of out­side ex­perts — seems to stem from a se­ries of meet­ings be­tween the com­pa­ny and Dunn dat­ing back as far as 2019, STAT re­ports, when the Cam­bridge, MA drug­mak­er launched a se­cret cam­paign dubbed Pro­ject Onyx to win ap­proval for ad­u­canum­ab.

Aaron Kessel­heim

Those meet­ings led to dis­cus­sions with of­fi­cials in Dunn’s of­fice about the use of the ac­cel­er­at­ed ap­proval path­way to move Aduhelm through the line. The use of that path­way is what Har­vard med­ical school pro­fes­sor and ad­comm mem­ber Aaron Kessel­heim at­trib­uted to his de­par­ture from the FDA com­mit­tee. By June 2019, just a month af­ter Bio­gen ex­ec­u­tives met with Dunn, of­fi­cials in his of­fice pro­posed the ac­cel­er­at­ed ap­proval route — de­spite doc­u­ments from the FDA that said the agency first dis­cussed the pos­si­bil­i­ty of ac­cel­er­at­ed ap­proval on March 31, ac­cord­ing to the STAT re­port.

Bil­ly Dunn

“It was clear that Bil­ly Dunn was an al­ly, so the job for Bio­gen be­came fig­ur­ing out how to sup­port his ef­forts with­in the FDA,” a for­mer Bio­gen em­ploy­ee anony­mous­ly told STAT.

The FDA grant­ed ad­u­canum­ab — now mar­ket­ed as Aduhelm — ap­proval in ear­ly June, as the first drug to slow the pro­gres­sion of Alzheimer’s. In the years lead­ing up to the OK, near­ly every ef­fort to treat Alzheimer’s had failed, even as the num­ber of Amer­i­cans liv­ing with the dis­or­der grew to more than 6 mil­lion. The last ap­proved drug came in 2003 and on­ly tem­porar­i­ly boosts mem­o­ry. The ap­proval re­mains high­ly con­tro­ver­sial as the FDA ig­nored the near-unan­i­mous rec­om­men­da­tion of its ad­vi­so­ry com­mit­tee, which said Bio­gen cher­ry-picked da­ta af­ter the drug failed two clin­i­cal tri­als.

Al San­drock

Ad­u­canum­ab seemed dead in the wa­ter in 2019 when da­ta from those two clin­i­cal tri­als showed a flop on the pri­ma­ry end­points. Bio­gen’s stock dropped 30% and the com­pa­ny lost $16 bil­lion in mar­ket val­ue. When sci­en­tists lat­er found in post hoc analy­ses that the drug did demon­strate ef­fec­tive­ness against Alzheimer’s, Bio­gen reached out to Dunn and asked for his help. Near­ly im­me­di­ate­ly af­ter, chief sci­en­tist Al San­drock met with Dunn in Philadel­phia for an off-the-record, off-the-books meet­ing, STAT re­port­ed.

Dunn, now the di­rec­tor of the FDA’s of­fice of neu­ro­science, laid out a red car­pet for the com­pa­ny, of­fer­ing a hearty en­dorse­ment of the drug de­spite what Caleb Alexan­der, an epi­demi­ol­o­gist at Johns Hop­kins Uni­ver­si­ty and ad­comm mem­ber, called “dozens of red flags” in the da­ta in front of a room filled with skep­tics.

Dur­ing that No­vem­ber 2020 pan­el dis­cus­sion, Dunn brushed aside an FDA sta­tis­ti­cian’s con­cerns about the lack of ef­fi­ca­cy. His tone was deemed pro­mo­tion­al.

“At times, Dunn was ad­vo­cat­ing more strong­ly for Aduhelm than [Saman­tha] Budd Hae­ber­lein, the Bio­gen ex­ec­u­tive pre­sent­ing the com­pa­ny’s clin­i­cal da­ta,” the STAT sto­ry reads. “When she strug­gled to an­swer ques­tions posed by the pan­el, Dunn stepped in to re­spond.”

Three mem­bers of the FDA’s Pe­riph­er­al and Cen­tral Ner­vous Sys­tem Drugs Ad­vi­so­ry Com­mit­tee re­signed af­ter the ap­proval, with Kessel­heim call­ing it “prob­a­bly the worst drug ap­proval de­ci­sion in re­cent U.S. his­to­ry.”

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

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US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

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CMS spent more than $18B in four years on ac­cel­er­at­ed ap­provals with in­com­plete con­fir­ma­to­ry tri­als, in­spec­tor gen­er­al finds

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Some­one old, some­one new: Mod­er­na pro­motes CTO, raids No­var­tis for re­place­ment amid pipeline push

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The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.

Sens. Rand Paul (R-KY) and Cory Booker (D-NJ) (Olivier Douliery/Sipa USA (Sipa via AP Images)

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The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.