CDC, NIH, FDA lead­ers call for US-based clin­i­cal tri­al of small­pox drug in treat­ing mon­key­pox

With the ris­ing num­ber of mon­key­pox cas­es, lead­ing re­searchers at the CDC, FDA and NIH are call­ing on a ran­dom­ized clin­i­cal tri­al to see if an ap­proved small­pox drug is ef­fec­tive at treat­ing mon­key­pox.

No mon­key­pox treat­ments are ap­proved in the US, so pa­tients look­ing to get re­lief for their le­sions and oth­er symp­toms from the virus must go through a set of hur­dles to get the small­pox drug through a gov­ern­ment ex­pand­ed ac­cess pro­gram. Ap­proved for small­pox in 2018, the drug is mar­ket­ed as TPOXX by the biotech SIGA. The Eu­ro­pean Union ap­proved it for mon­key­pox in ad­di­tion to small­pox ear­li­er this year and the UK fol­lowed suit in Ju­ly.

In an opin­ion piece pub­lished in the New Eng­land Jour­nal of Med­i­cine on Wednes­day, gov­ern­ment re­searchers said the NIH’s Na­tion­al In­sti­tute of Al­ler­gy and In­fec­tious Dis­eases is work­ing with the AIDS Clin­i­cal Tri­als Group, which has over­seen stud­ies of HIV meds since the 1980s, to set up a clin­i­cal tri­al to test TPOXX for mon­key­pox.

But while NI­AID, ACTG and SIGA all con­firmed to End­points News via email that a US-based clin­i­cal tri­al of the drug is be­ing planned, they de­clined to say when it would start. Ac­tivists ar­gue the tri­al should have tak­en place be­fore mon­key­pox be­came a glob­al out­break be­cause the virus has been en­dem­ic in some coun­tries in Africa for years.

“Adults with mon­key­pox in­fec­tion, in­clud­ing peo­ple liv­ing with HIV, would be el­i­gi­ble to en­roll. NI­AID will share more in­for­ma­tion as it be­comes avail­able,” the NI­AID said in an emailed state­ment.

“Those tri­als should have been ob­vi­ous­ly planned for well be­fore a cur­rent out­break. This is what the job of pan­dem­ic pre­pared­ness is. We ob­vi­ous­ly had mil­lions of dos­es stock­piled for this pur­pose and it is in­sane that the fed­er­al gov­ern­ment didn’t ac­tu­al­ly have ef­fi­ca­cy tri­als planned for it,” James Krel­len­stein, strat­e­gy & pol­i­cy man­ag­ing di­rec­tor for the or­ga­ni­za­tion PrEP4All, told End­points in a phone in­ter­view.

The re­searchers analo­gize the lack of ap­proved meds for the cur­rent mon­key­pox out­break to the ear­ly years of the HIV epi­dem­ic in the 1980s, when ther­a­pies had been de­vel­oped, but the process for ap­prov­ing their use in hu­mans was “painful­ly slow.” An eth­i­cal bal­ance was need­ed to en­sure pa­tients had ac­cess while al­so “up­hold­ing the re­spon­si­bil­i­ty” of en­sur­ing they were safe and ef­fec­tive, the re­searchers wrote Wednes­day in NE­JM.

“Now, 34 years lat­er, we are faced with an un­can­ni­ly sim­i­lar sit­u­a­tion,” they wrote. The au­thors of the piece in­clude John Brooks, CMO for the CDC’s Di­vi­sion of HIV Pre­ven­tion; De­bra Birnkrant, di­rec­tor of the Di­vi­sion of An­tivi­rals with­in the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search; and Pe­ter Kim, deputy di­rec­tor of the Ther­a­peu­tic Re­search Pro­gram in the Di­vi­sion of AIDS at NI­AID.

Or­ga­ni­za­tions such as PrEP4All have called for the re­moval of re­stric­tions to the drug so pa­tients can get the med quick­er and more eas­i­ly as mon­key­pox case counts climb past 25,000 across 83 coun­tries. The US is one of the biggest out­break re­gions and three states — Illi­nois, New York and Cal­i­for­nia — have de­clared it a pub­lic health emer­gency.

Pri­or to the cur­rent glob­al out­break, the NIH had be­gun plan­ning for a ran­dom­ized clin­i­cal tri­al of the drug in the De­mo­c­ra­t­ic Re­pub­lic of the Con­go, but in their NE­JM piece, the re­searchers cite the need for a US-based tri­al since cur­rent world­wide cas­es are of a dif­fer­ent clade than what is seen in the DRC.

The US has ac­cess to about 1.7 mil­lion cours­es of the drug through the Strate­gic Na­tion­al Stock­pile, and BAR­DA has a con­tract with SIGA to re­plen­ish the cours­es when they ex­pire, ac­cord­ing to the com­pa­ny. As of last week, 10,000 cours­es of the drug had been sent to states and cities up­on re­quest, the De­part­ment of Health and Hu­man Ser­vices told NPR.

A SIGA spokesper­son said the com­pa­ny is “aware of the plans for a clin­i­cal tri­al and is work­ing with NI­IAD [sic] to ad­vance a place­bo-con­trolled study of tecovir­i­mat in the treat­ment of mon­key­pox.” SIGA re­ports quar­ter­ly earn­ings on Thurs­day.

SIGA can­celed a sched­uled in­ter­view be­tween sci­ence chief Den­nis Hru­by, CEO Phillip Gomez and End­points, say­ing that it “would pre­fer to wait for pub­li­ca­tion of the full ar­ti­cle in NE­JM be­fore com­ment­ing much fur­ther on any specifics.”

Hru­by told NBC News last month that plans for large clin­i­cal tri­als were in ad­vanced stages in Cana­da, the UK and the EU. Hru­by told the news out­let that SIGA might not re­ly on US tri­al da­ta to sub­mit to the FDA, but rather look to com­bined find­ings in oth­er coun­tries and safe­ty da­ta from glob­al com­pas­sion­ate-use pro­grams.

In their NE­JM piece, the CDC, FDA and NIH re­searchers wrote that they “an­tic­i­pate that these tri­als will pro­vide da­ta need­ed for clin­i­cal and reg­u­la­to­ry de­ci­sion mak­ing in the Unit­ed States.”

SIGA’s drug was ap­proved in the US in 2018 un­der the “An­i­mal Rule,” which al­lows drugs for se­ri­ous or life-threat­en­ing con­di­tions to be green­lit when hu­man stud­ies are deemed un­eth­i­cal. Ef­fi­ca­cy is es­tab­lished in an­i­mal mod­els of the hu­man dis­ease. The drug was ap­proved based on ef­fi­ca­cy da­ta gath­ered from in­fect­ing non­hu­man pri­mates with mon­key­pox virus and rab­bits with rab­bit­pox virus, as well as safe­ty da­ta from more than 400 healthy adult vol­un­teers.

As the mon­key­pox out­break spreads to more than 6,000 re­port­ed cas­es in the US, peo­ple at high­est risk have been scram­bling to get vac­ci­nat­ed against the virus. There is one jab ap­proved in the US, Bavar­i­an Nordic’s Jyn­neos, which is in lim­it­ed sup­plies in the US af­ter a na­tion­al stock­pile large­ly evap­o­rat­ed in re­cent years. A small­pox vac­cine, ACAM2000, is al­so be­ing used in cer­tain in­stances.

Mean­while, Mod­er­na lead­ers said Wednes­day that the pan­dem­ic-in­fa­mous biotech is look­ing in­to a po­ten­tial mon­key­pox pro­gram.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,600+ biopharma pros reading Endpoints daily — and it's free.

Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

Endpoints Premium

Premium subscription required

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

Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,600+ biopharma pros reading Endpoints daily — and it's free.

CBER Director Peter Marks (Susan Walsh/AP Images)

FDA ad­vi­so­ry com­mit­tee votes unan­i­mous­ly in fa­vor of bi­va­lent Covid shots re­plac­ing pri­ma­ry se­ries

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all current vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

The vote marks an effort to clear up confusion around varying formulations and dosing schedules for current primary series and booster vaccines, as well as “get closer to the strains that are circulating,” according to committee member Paul Offit, professor of pediatrics at the Children’s Hospital of Philadelphia.

FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

No­var­tis' ap­proved sick­le cell dis­ease drug fails to beat place­bo in PhI­II

Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

The Swiss pharma giant unveiled early data from the ongoing STAND Phase III study on Friday, saying that crizanlizumab showed no statistically significant difference between the drug at two different dose levels compared to placebo in annualized rates of vaso-occlusive crises that lead to a healthcare visit over the first year since being randomized into the trial.

Post-hoc analy­sis: EMA's CHMP re­jects Ipsen's po­ten­tial drug for rare ge­net­ic dis­ease

The European Medicines Agency’s Committee for Medicinal Products for Human Use on Friday rejected Ipsen Pharma’s potential treatment for a rare genetic disease known as fibrodysplasia ossificans progressiva (FOP), which causes extra bone to form outside the skeleton.

The EMA said on its website that it could not draw any firm conclusions on the benefits of the French biopharma’s Sohonos (palovarotene), which selectively targets the retinoic-acid receptor gamma (RARγ), “as the applicant’s conclusion was based on a post-hoc analysis which was neither scientifically nor clinically justified and pre-specified study objectives were not met.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,600+ biopharma pros reading Endpoints daily — and it's free.

Steve Harr, Sana Biotechnology CEO

Four years in, Sana gets first FDA go-ahead to bring can­cer treat­ment in­to the clin­ic

Sana Biotechnology is finally headed to the clinic.

Thursday afternoon, the biotech announced the FDA had cleared its application to start a clinical trial for its allogeneic, or “off-the-shelf,” CAR-T cell therapy targeting the antigen CD19 for patients with B-cell lymphomas and leukemias. Sana said its therapy, dubbed SC291, was designed to evade the immune system, which could help cell therapy produce a more durable response in patients, a concern that has followed such off-the-shelf therapies that use donor cells as opposed to a patient’s own cells.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,600+ biopharma pros reading Endpoints daily — and it's free.