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.

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

The notorious drug testing company Valisure, which has made a name for itself by forcing FDA’s hand with some of its safety-related uncoverings, received a letter this week after the FDA uncovered violations at its Connecticut-based testing lab in 2021.

The letter, which was sent on Dec. 5, stated that the FDA is “concerned” that Valisure was not aware of  drug supply chain security requirements.

Republicans have taken a stand against the pandemic era habit of lax work-from-home schedules. Now that they’ve wrestled control of the House majority, the FDA’s leadership is playing ball, sending many of the agency’s more than 18,000 employees back to their desks early next year.

Whether this exodus back to White Oak in Silver Spring, MD (many staff will still be allowed to work from home for multiple days per week) will mean more defections to industry and elsewhere remains to be seen.

The generics manufacturer Lupin has been given another Form 483 from the FDA this year.

US regulators inspected Lupin’s pharmaceutical manufacturing site in the town of Mandideep, India from Nov. 14 through Nov. 23, with the 14-page report marking 16 observations.

The inspection report stated that the site did not have the appropriate controls over its computer systems to ensure that changes in “master production” or records are only done by authorized personnel, along with written procedures not being established to conduct annual reviews of records associated with drug batches.

The FDA is struggling to remove drugs from the marketplace that don’t show effectiveness in late stage trials, new JAMA analyses found, thanks to the persistent tension between speed and confidence in early clinical data.

Congress, regulated industry and patients have urged the FDA to shorten the amount of time that the market has to wait for drugs to become available that may help severe and prevalent diseases – and the FDA has listened, offering up a quick accelerated approval pathway that’s frequently used by new cancer drugs.