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.

After the FDA lambasted their PD-1 ahead of an adcomm earlier this week, Incyte ran into new trouble Thursday as ODAC panelists voted against an accelerated OK by a wide margin.

Members of the Oncologic Drugs Advisory Committee recommended with a 13-4 vote to defer a regulatory decision on Incyte’s retifanlimab until after more data can be collected from a placebo-controlled trial. The PD-1 therapy is due for a PDUFA date in late July after receiving priority review earlier this year.

The FDA on Thursday called to include those with incurable cancers (when there is no potential for cure or for prolonged/near normal survival) in appropriate clinical trials, regardless of whether they have received existing alternative treatments.

Historically, many cancer clinical trials have required that participating patients previously received multiple therapies, according to Richard Pazdur, director of the FDA’s Oncology Center of Excellence.

Gene therapy companies have faced huge hurdles trying to deliver healthy genes into muscular dystrophy patients’ muscle cells, so here’s an idea: Why don’t we just replace the muscle cells themselves?

Over the last two years, Vita Therapeutics has been exploring that possibility, building on early stem cell work from Johns Hopkins professor Peter Andersen. And on Tuesday they announced a $32 million Series A to begin to move their first therapy into the clinic, where they hope it will help rebuild muscle in patients with a type of dystrophy that afflicts the arms and legs.