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.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Justin Klee (L) and Joshua Cohen, Amylyx co-CEOs (Cody O'Loughlin/The New York Times; courtesy Amylyx)

Ad­vo­cates, ex­perts cry foul over Amy­lyx's new ALS drug, cit­ing is­sues with price, PhI­II com­mit­ment

Not 24 hours after earning the first ALS drug approval in five years, Amylyx Pharmaceuticals’ Relyvrio is already drawing scrutiny. And it’s coming from multiple fronts.

In an investor call Friday morning, Amylyx revealed that it would charge about $158,000 per year, a price point that immediately drew backlash from ALS advocates and some outside observers. The cost reveal had been highly anticipated in the immediate hours after Thursday evening’s approval, though Amylyx only teased Relyvrio would cost less than previously approved drugs.

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Up­dat­ed: Al­ny­lam re­in­forces APOL­LO-B patisir­an da­ta be­fore head­ing to the FDA

Weeks after uncorking some mostly positive data for patisiran in transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, Alnylam is bolstering its package with new exploratory and subgroup data before shipping it off to regulators.

The RNAi drug maintained “generally consistent” benefits in efficacy and quality of life across several prespecified subgroups at month 12, Alnylam announced on Friday afternoon, including age, baseline tafamidis use, ATTR amyloidosis type, baseline six-minute walk test score and others.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Hubertus von Baumbach, EFPIA president (Credit: EFPIA via YouTube)

Eu­ro­pean phar­ma group wants to cre­ate PRV-like sys­tem to spur an­tibi­otics R&D

New research funded by a European pharma industry group is looking to reinvigorate antimicrobial R&D with a system that’s similar to the priority review voucher systems in the US, which spurs new research in rare pediatric diseases, rare tropical diseases and medical countermeasures.

As the need for novel antibiotics is urgent, EFPIA is calling for a Transferable Exclusivity Extension (TEE) voucher system where developers of novel antibiotics can win a voucher that can then be used to extend the exclusivity of another drug for a period of time, or sold to another company, thereby paying for the antibiotic research.

Jerome Durso, Intercept Pharmaceuticals CEO

In­ter­cep­t's OCA fails a PhI­II NASH tri­al, rais­ing fresh doubts about its years­long quest for an OK

Intercept Pharmaceuticals has run into another big setback in its yearslong quest to win an approval for OCA in NASH. The biotech put out word Friday morning that its Phase III REVERSE study failed the primary endpoint for the liver disease, sending its share price into a tailspin.

There was no significant improvement in fibrosis among the patients suffering from cirrhosis who were treated with obeticholic acid, with investigators hunting for a minimum 1-stage histological improvement in the disease after 18 months of therapy.

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Some­one old, some­one new: Mod­er­na pro­motes CTO, raids No­var­tis for re­place­ment amid pipeline push

Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in the cockpit.

The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.

Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

George Church (courtesy EnPlusOne BioSciences)

George Church, Wyss sci­en­tists and North­pond chal­lenge con­ven­tion­al RNA man­u­fac­tur­ing with new biotech

RNA medicine has been at the forefront for the past few years, with the first RNA silencing therapy approved in 2018, and mRNA Covid vaccines following after. But flying under the radar has been the process of actually making RNA for these treatments.

That’s what Daniel Wiegand and Jonathan Rittichier have been working on in George Church’s lab for the past six years.

Friday morning, they unveiled EnPlusOne Biosciences, a biotech built on their RNA synthesis platform. Wiegand will serve as the Watertown, MA-based biotech’s CEO, and Rittichier will be CSO. And no different from his other startups, Church will be acting as scientific advisor. Its fourth co-founder, Dan Ahlstedt, joined through a Harvard Business School program, and will be COO.

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