The FDA's in­sid­er re­view on ad­u­canum­ab was all about pol­i­tics, not sci­ence, and it threat­ens pa­tients and the bio­phar­ma in­dus­try alike

Bioreg­num Opin­ion Col­umn by John Car­roll

The FDA de­serves ku­dos for draw­ing a line in the sand over their re­view of Covid-19 vac­cines. They’ve made it clear — af­ter deep skep­ti­cism be­gan to ap­pear fol­low­ing the de­ba­cle over con­va­les­cent plas­ma — just what they will need to see be­fore hand­ing out an EUA, thus sav­ing the agency’s rep for en­forc­ing stan­dards es­sen­tial to main­tain­ing pub­lic trust in drugs.

That same in­tegri­ty, though, has gone miss­ing from the FDA’s stance on Bio­gen’s Alzheimer’s drug ad­u­canum­ab. De­spite a sta­tis­ti­cal analy­sis that high­lights the con­flict­ing na­ture of the Bio­gen $BI­IB da­ta, a post hoc dump­ster dive op­er­a­tion to find sup­port­ive da­ta and a move to shine up small co­hort re­sults as back­up proof of ef­fi­ca­cy, the FDA di­vi­sion re­spon­si­ble for Alzheimer’s chose to en­dorse adu for use among mil­lions of pa­tients.

We’ve been here be­fore. The Sarep­ta ap­proval lead­ing to mar­ket­ing au­tho­riza­tion — with a la­bel that clear­ly states their first, very ex­pen­sive, Duchenne MD drug re­mains ex­per­i­men­tal — is a per­ma­nent black eye when it comes to in­dus­try stan­dards. What fol­lowed just made it all much, much worse — and ap­pears to be about ready to hap­pen again in an in­fi­nite­ly larg­er pa­tient pop­u­la­tion.

At the time, as I found out fair­ly re­cent­ly, the FDA’s Janet Wood­cock re­peat­ed­ly told col­leagues that an ap­proval for Sarep­ta was a once-off de­ci­sion. She signed off on bio­mark­er da­ta from a tiny study one time. The next time Sarep­ta would have to do some­thing like a walk test with more boys. She want­ed re­al da­ta.

On­ly that nev­er hap­pened. What did hap­pen: The FDA reg­u­la­tors in charge adopt­ed the bio­mark­er da­ta on dy­s­trophin pro­duc­tion as a low bar for an ap­proval, and once they got a naysay­er out of the way who hand­ed out a CRL for their sec­ond app, the new reg­u­la­tors in charge waved it through.

So we shouldn’t con­sid­er this some sort of once-off just to give Alzheimer’s pa­tients a drug they can use un­til some­thing bet­ter comes along.

This is a prece­dent that can be used again and again, low­er­ing the bar on Alzheimer’s da­ta that oth­ers can jump over as well.

What else did we learn from Sarep­ta?

One, when you catch a ‘Hail Mary’ pass, there’s no need to do some­thing like ac­tu­al­ly meet FDA time­lines for a full piv­otal tri­al to con­firm the weak signs of ef­fi­ca­cy you’re see­ing. The biotech drug their heels on that for­got­ten front for years, and the FDA did noth­ing about it.

We see this sort of thing reg­u­lar­ly. Once a drug wins any kind of quick OK, it doesn’t al­ways just dis­ap­pear once the re­quired Phase III fol­lowup — in­evitably re­quir­ing years — turns out to be a flop.

An un­met med­ical need like Alzheimer’s is a ter­ri­ble thing. But when FDA stan­dards go in the trash bin on the way in­to an ad­vi­so­ry pan­el meet­ing, it hurts every­one — pa­tients and in­dus­try alike. If you de­stroy pa­tients’ trust in reg­u­la­to­ry de­ci­sions, as the FDA ap­pears de­ter­mined to do here, you un­der­mine all mar­ket­ed ther­a­peu­tics.

We’ll find out what the FDA pan­el thinks of ad­u­canum­ab lat­er to­day. Most drug de­vel­op­ers al­ready know that the FDA is be­ing pushed by po­lit­i­cal rea­sons here. The sci­ence sim­ply doesn’t back it up.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

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S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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FDA re­view­ers en­dorse J&J sin­gle-dose shot, lay­ing path for 3rd US vac­cine

J&J’s single-dose vaccine may not have produced quite the stellar numbers of the mRNA shots, but it still won a ringing endorsement from FDA reviewers, who argued in briefing documents that it could provide robust protection against the still-raging virus.

The FDA confirmed that across just under 40,000 volunteers, the vaccine proved 66% effective at preventing symptomatic Covid-19, including 72% effective in the United States. Although that’s short of the 95% figures put up by Moderna and Pfizer-BioNTech, the shot was still 85% effective at stopping severe disease 28 days after administration. There were seven deaths in the placebo group — zero in the vaccine group.

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Biden is look­ing be­yond Wood­cock or Sharf­stein for FDA com­mis­sion­er — re­port

Neither Janet Woodcock nor Joshua Sharfstein is likely to be nominated as the permanent FDA commissioner, Steve Usdin at BioCentury reports.

The White House is looking for alternatives to Woodcock, the acting chief and longtime CDER director, after opposition from several Democratic senators who are calling on others to block her nomination if her name is put forth, according to Usdin. Sharfstein, the former principal deputy FDA commissioner and current Johns Hopkins professor, is out of the running altogether.