Dan Menichella (AP Photo/Andrew Harnik)

UP­DAT­ED: Food or drug? FDA blasts Flag­ship-backed mi­cro­bio­me play­er’s ‘non-IND’ Covid-19 tri­al

When Kalei­do Bio­sciences un­veiled re­sults from a mul­ti-cen­ter, open la­bel, con­trolled clin­i­cal study test­ing its mi­cro­bio­me prod­uct in Covid-19 pa­tients back in March, the biotech tout­ed it as a “non-IND” tri­al that yield­ed pos­i­tive re­sults and paved the way for an IND.

But it turned out that the FDA was not im­pressed with that tac­tic.

The agency has is­sued a warn­ing let­ter to Kalei­do blast­ing its “fail­ure to sub­mit INDs for the con­duct of clin­i­cal in­ves­ti­ga­tions with an in­ves­ti­ga­tion­al new drug” that falls un­der sec­tion 505 of the fed­er­al Food, Drug, and Cos­met­ic Act. Kalei­do now has 15 days to ex­plain it­self or re­port the ac­tions it’s tak­en to pre­vent sim­i­lar vi­o­la­tions — or else face reg­u­la­to­ry ac­tion.

“We are re­view­ing the let­ter cur­rent­ly and look for­ward to pro­vid­ing a re­sponse with­in the giv­en time­frame and con­tin­u­ing our dis­cus­sions with the FDA,” CEO Dan Menichel­la, to whom the let­ter was di­rect­ly ad­dressed, said in an emailed state­ment.

Kalei­do was well aware of the FDA’s ob­jec­tions, ac­cord­ing to the let­ter, which stat­ed that in­spec­tor Kent Con­for­ti had pre­sent­ed a Form 483 and dis­cussed it with staff in ear­ly March.

Reg­u­la­tors re­ceived a re­sponse on March 23, the eve of Kalei­do’s study re­sult an­nounce­ment, in which Kalei­do ar­gued that KB109, the syn­thet­ic gly­can be­ing test­ed in the study, was in fact “a food rather than a drug.”

Specif­i­cal­ly, Kalei­do ar­gued that the in­ves­ti­ga­tions were con­duct­ed “to eval­u­ate the ef­fect of KB109 on the mi­cro­bio­me[,] as well as to de­ter­mine the safe­ty and tol­er­a­bil­i­ty of KB109 in the dis­eased pop­u­la­tion[,]” that is, hu­man sub­jects with mild to mod­er­ate COVID-19, and thus it in­ves­ti­gat­ed KB109 for use as a food rather than a drug.

To sup­port this ar­gu­ment, Kalei­do as­sert­ed that it did not in­tend for these “food stud­ies” to eval­u­ate whether KB109 would be an ef­fec­tive treat­ment or mit­i­ga­tion for COVID-19; rather, Kalei­do ar­gued that the sec­ondary end­points in these stud­ies were de­ter­mi­na­tive of safe­ty and tol­er­a­bil­i­ty. For this rea­son, Kalei­do stat­ed that KB109 was a food in­ter­ven­tion, and con­sis­tent with Agency guid­ance, it was ap­pro­pri­ate to con­duct these stud­ies with­out an IND in a pop­u­la­tion with COVID-19.

The pro­to­col, dubbed Pro­to­col K031-120 and Pro­to­col K032-120, and Kalei­do’s press re­leas­es sug­gest­ed oth­er­wise, the FDA said. Not on­ly was Kalei­do’s ob­jec­tive to com­pare the safe­ty and ef­fi­ca­cy of KB109 in com­bi­na­tion with sup­port­ive self-care un­der quar­an­tine against sup­port­ive self-care alone, the biotech al­so mea­sured par­tic­i­pants’ symp­toms and health­care uti­liza­tion among oth­er things like bio­mark­ers and their gut mi­cro­bio­me struc­ture.

To the FDA, that sounds a lot like the ef­fi­ca­cy end­points it has rec­om­mend­ed in its guid­ances to help spon­sors nav­i­gate de­vel­op­ing Covid-19 treat­ments.

For Pro­to­col K032-120, while some end­points could be con­sid­ered safe­ty out­comes that might be eval­u­at­ed on­ly to en­sure that treat­ment with KB109 was not wors­en­ing the course of COVID-19, oth­er end­points (for ex­am­ple, pro­por­tion of sub­jects ex­pe­ri­enc­ing hos­pi­tal ad­mis­sion dur­ing the fol­low-up pe­ri­od, mea­sures of health­care uti­liza­tion, and pro­por­tion of sub­jects with oxy­gen sat­u­ra­tion be­low nor­mal) clear­ly as­sessed the use of KB109 in com­bi­na­tion with SCC for the treat­ment or mit­i­ga­tion of COVID-19.

The ar­gu­ment for de­scrib­ing KB109 as a med­ical food fails be­cause no dis­tinc­tive nu­tri­tion­al re­quire­ments have been es­tab­lished for Covid-19, which is a pre­req­ui­site for defin­ing med­ical food, the FDA wrote. Be­sides, the stud­ies went be­yond “di­etary man­age­ment” and eval­u­at­ed a host of oth­er ef­fects on Covid-19 in­fec­tion.

“As Kalei­do not­ed in its re­sponse to the Form FDA 483, whether an in­ves­ti­ga­tion­al ar­ti­cle is a drug or a food de­pends on the in­tent of the in­ves­ti­ga­tion,” its let­ter read. And KB109 was used in these clin­i­cal in­ves­ti­ga­tions as a drug be­cause it was “stud­ied for use in the mit­i­ga­tion and treat­ment of COVID-19.”

The FDA asked Kalei­do to get in line, ad­dress the de­fi­cien­cies and set up pro­ce­dures to en­sure com­pli­ance with reg­u­la­tions in the fu­ture.

Ed­i­tor’s Note: This sto­ry has been up­dat­ed to in­cor­po­rate a com­ment from Kalei­do.

Why it Works: Man­u­fac­tur­ing a Vac­cine in a Mul­ti-Prod­uct Fa­cil­i­ty.

COVID-19 launched the pharmaceutical industry to the frontline in the battle against the fast-spreading global pandemic. The goal: distribute a safe, effective vaccine as quickly as possible. Major players in the vaccine market needed to partner with contract development and manufacturing organizations (CDMOs) to achieve the goal of mass vaccine quantities under expedited timelines. With CDMOs stepping up to play a critical role in the vaccine manufacturing process, multi-product CDMO facilities took the spotlight. Partnerships quickly formed as the race to save lives and fight a pandemic was on.

Habib Dable, Acceleron CEO

Days of heat­ed ru­mors cul­mi­nate in a re­port that Ac­celeron is in ad­vanced buy­out talks

Days of frothy rumors about possible M&A discussions at Acceleron were capped late Friday with a Bloomberg report asserting that the biotech company is in advanced talks for an $11 billion buyout deal.

Bloomberg was unable to identify any bidders in the deal, but speculation has been running rampant that the surging value of Acceleron stock had to be the result of leaks around the auction of the company. As of early Monday morning, we’re still awaiting the final word.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 118,600+ biopharma pros reading Endpoints daily — and it's free.

Merck CEO Rob Davis

Mer­ck emerges as lead bid­der in po­ten­tial Ac­celeron buy­out with deal pos­si­ble this week — re­port

With rumors swirling about a potential buyout of biotech Acceleron and its lead PAH drug sotatercept, market watchers have been keeping close tabs on industry movers and shakers due up for an expensive bolt-on. According to a new report, it appears Merck may be the one.

Merck is in “advanced talks” on a deal to acquire Cambridge, MA-based Acceleron in what previous reports pegged as a potential $11 billion buyout, the Wall Street Journal reported Monday. A deal could come as early as this week, according to the Journal.

Alexander Lefterov/Endpoints News

The coro­n­avirus vac­cine that the world for­got could still help save it

Back at the beginning of the pandemic — back when we still called the virus “novel” and a single case in Washington state could make headlines — there emerged the story of the coronavirus vaccine that the world forgot.

It was an allegory for our pandemic ill-preparedness. At a time when the world had been caught so flat-footed, there were a pair of scientists who had seen the crisis coming, lab-coated Cassandras with an antidote if only the world had listened sooner.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Peter Marks (Jim Lo Scalzo/Pool via AP Images)

Tur­moil at CBER: Pe­ter Marks grabs con­trol of FDA's Of­fice of Vac­cines ahead of 2 key ca­reer leader de­par­tures

FDA’s top vaccine official Peter Marks is pulling the plug on a months-long transition for two top career vaccine officials who abruptly called it quits in late August.

Marion Gruber, director of the FDA’s Office of Vaccines Research & Review and 32-year veteran of the agency, her deputy director Phil Krause, announced their departures and then raised concerns with Covid-19 booster shots ahead of and during a recent Covid-19 booster vaccine advisory committee.

Safe­ty fears force Pfiz­er to change piv­otal DMD gene ther­a­py tri­al pro­to­col

As one of the biggest players in an increasingly packed gene therapy space, Pfizer has taken an early lead over specialists like Sarepta in taking a Duchenne muscular dystrophy (DMD) candidate into late-stage testing. But new safety fears have led Pfizer to scale back that trial, cutting out patients with certain genetic mutations.

Pfizer has amended its enrollment protocol for a Phase III test for gene therapy fordadistrogene movaparvovec in DMD after investigators flagged severe side effects tied to specific mutations, according to a letter the drugmaker sent to Parent Project Muscular Dystrophy, a patient advocacy group.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 118,600+ biopharma pros reading Endpoints daily — and it's free.

Albert Bourla, Pfizer CEO (John Thys, Pool via AP Images)

Covid-19 roundup: Pfiz­er/BioN­Tech sub­mit vac­cine da­ta to FDA for younger chil­dren; Doc­tors kept pre­scrib­ing hy­drox­y­chloro­quine

Pfizer and BioNTech said Tuesday they submitted to FDA positive data from a Phase II/III trial of their Covid-19 vaccine in children aged 5 to less than 12 years old.

A formal EUA submission for the vaccine in these children is expected to follow “in the coming weeks,” the companies said in a statement.

The trial of 2,268 healthy participants aged 5 to less than 12 years old showed the vaccine was safe and elicited robust neutralizing antibody responses using a two-dose regimen of 10 μg doses, which is one-third the dose that’s administered to adults.

Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Ciaran McCrickard)

Seiz­ing Aduhelm prece­dent, Bio­gen, Ei­sai get the ball rolling on an­oth­er ac­cel­er­at­ed Alzheimer's ap­proval

Biogen — together with partners at Eisai — will be the first to breeze down that Alzheimer’s trail it blazed with the FDA’s historic and controversial accelerated approval of Aduhelm.

Eisai disclosed it’s initiated a rolling BLA submission for lecanemab, or BAN2401, the anti-amyloid beta antibody that Biogen has long touted as a follow-on to Aduhelm (then aducanumab). Following the precedent that the agency has now set, the two companies are gunning for an OK based on data suggesting that the drug could lower amyloid beta plaques.

Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Ciaran McCrickard)

New ARIA cas­es dog Bio­gen's Aduhelm launch in an­oth­er po­ten­tial blow to block­buster hopes — an­a­lyst

Perhaps anticipating a walkover with an FDA approval in hand, Biogen has instead faced a wall of pushback over its controversial Alzheimer’s med Aduhelm. With payers and clinics largely staying away, Biogen’s drug is posting some troubling safety signals that could derail the launch even further.

In a note to clients Friday, analysts from Baird revealed new safety data from the FDA’s Adverse Event Reporting System (FAERS) showing a troubling recurrence of ARIA in a crop of patients who have been dosed with Aduhelm.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 118,600+ biopharma pros reading Endpoints daily — and it's free.