FDA up­dates Covid-19 clin­i­cal tri­als guid­ance to ad­dress se­ri­ous ad­verse events

The FDA last week up­dat­ed its guid­ance on con­duct­ing clin­i­cal tri­als amid the coro­n­avirus dis­ease pan­dem­ic to ad­dress how and when spon­sors and ap­pli­ca­tion hold­ers should re­port se­ri­ous ad­verse events (SAE).

The lat­est up­date to the guid­ance comes just days af­ter FDA added new ques­tions and an­swers to the doc­u­ment ad­dress­ing the use of al­ter­nate lab­o­ra­to­ry or imag­ing cen­ters, video con­fer­enc­ing and post­mar­ket­ing stud­ies.

Se­ri­ous ad­verse events

The up­dat­ed guid­ance in­cludes two new ques­tions and an­swers on se­ri­ous ad­verse event re­port­ing re­quire­ments in dif­fer­ent cir­cum­stances.

The first ques­tion ad­dress­es sit­u­a­tions where a com­pa­ny study­ing an al­ready ap­proved drug to treat COVID-19 un­der an in­ves­ti­ga­tion­al new drug ap­pli­ca­tion (IND) re­ceives a spon­ta­neous re­port of a se­ri­ous ad­verse event stem­ming from the prod­uct’s off-la­bel use in clin­i­cal prac­tice to treat Covid-19.

FDA ex­plains that se­ri­ous ad­verse events that oc­cur in clin­i­cal prac­tice “must be re­port­ed in ac­cor­dance with the ap­plic­a­ble post-mar­ket­ing re­port­ing re­quire­ments,” whether or not the ad­verse event is in­clud­ed in la­bel­ing to the ap­pro­pri­ate FDA data­base, the Vac­cine Ad­verse Event Re­port­ing Sys­tem (VAERS) for vac­cines and the FDA Ad­verse Event Re­port­ing Sys­tem (FAERS) for drugs and bi­o­log­ics.

When the se­ri­ous ad­verse event oc­curs dur­ing a clin­i­cal tri­al, FDA says the event “must be re­port­ed as an IND safe­ty re­port … if they are un­ex­pect­ed and the spon­sor de­ter­mines that there is a rea­son­able pos­si­bil­i­ty that the drug caused the SAE.”

“Re­gard­less of whether an SAE oc­curs in the course of clin­i­cal prac­tice or dur­ing a clin­i­cal tri­al, and re­gard­less of where it is first re­port­ed, [a new drug ap­pli­ca­tion or bi­o­log­ics li­cense ap­pli­ca­tion] hold­er who is al­so the spon­sor of an IND in­ves­ti­gat­ing the same drug for COVID-19 is re­spon­si­ble for mon­i­tor­ing the safe­ty of its drug and eval­u­at­ing all ac­cu­mu­lat­ing safe­ty da­ta,” FDA writes, adding that if that da­ta in­di­cat­ed there may be a new se­ri­ous risk as­so­ci­at­ed with the drug that an IND safe­ty re­port must be filed.

In the sec­ond ques­tion, FDA ex­plains how spon­sors study­ing drugs for non-Covid-19 in­di­ca­tions should han­dle re­port­ing se­ri­ous ad­verse events as­so­ci­at­ed with Covid-19 dur­ing the tri­al.

FDA again ex­plains that spon­sors are re­quired to re­port any se­ri­ous ad­verse events that are un­ex­pect­ed and could rea­son­ably have been caused by the drug.

As such, FDA says that spon­sors must de­ter­mine whether the in­ves­ti­ga­tion­al drug “might be causal­ly re­lat­ed to a SAE as­so­ci­at­ed with COVID-19,” though the agency ac­knowl­edges that do­ing so “like­ly re­quires more than sin­gle or even a few cas­es.”

For ran­dom­ized con­trolled tri­als, FDA says spon­sors should com­pare the rate of ob­served se­ri­ous ad­verse events in par­tic­i­pants with Covid-19 in the in­ves­ti­ga­tion­al to those in the con­trol arm of the study. Be­cause such as­sess­ments would in­volve un­blind­ed da­ta, FDA says they should on­ly be done by a da­ta mon­i­tor­ing com­mit­tee or a “fire­walled” and in­de­pen­dent spe­cial­ly con­sti­tut­ed safe­ty com­mit­tee.

For non­ran­dom­ized stud­ies, FDA says spon­sors should com­pare the rate of se­ri­ous ad­verse events and mor­tal­i­ty for tri­al par­tic­i­pants di­ag­nosed with Covid-19 to a sim­i­lar ex­ter­nal pop­u­la­tion.

“If the dif­fer­ence in SAEs across treat­ment arms or com­pared to an ex­ter­nal pop­u­la­tion sug­gests a causal re­la­tion­ship be­tween the in­ves­ti­ga­tion­al prod­uct and the SAEs in sub­jects di­ag­nosed with COVID-19, this find­ing must be sub­mit­ted to FDA as an IND safe­ty re­port,” FDA writes.


For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

Endpoints Premium

Premium subscription required

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

Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Caught in a stand­off with its con­tract man­u­fac­tur­er over Covid-19 vac­cine, In­ovio files suit in an at­tempt to break free while ri­vals race ahead

Inovio was one of the first vaccine developers to snag attention for a jab that their execs said promised to end the Covid-19 pandemic. Using their own unique DNA tech, CEO Joseph Kim said it took just 3 hours to work it out.

But while rivals are racing to the finish line with ambitious plans to make vast quantities of their vaccines with billions of dollars of deals, Inovio is still stuck at the starting line on manufacturing.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.