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.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

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Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

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Maralixibat’s roots trace back to Lumena, which was snapped up by Shire for $260 million-plus back in 2014. While the candidate had failed mid-stage studies at Shire, Mirum believes better trial design and patient selection will deliver the wins it needs. The drug is currently in development for Alagille syndrome (a condition called ALGS in which bile builds up in the liver), progressive familial intrahepatic cholestasis (PFIC, which causes progressive liver disease) and biliary atresia (a blockage in the ducts that carry bile from the liver to the gallbladder).

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a specific market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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