Search­ing for HIV cure, Gilead­'s new 'shock and kil­l' com­bo swats back lethal virus in mon­keys

A promi­nent group of sci­en­tif­ic in­ves­ti­ga­tors has tak­en an­oth­er step to­ward a pos­si­ble even­tu­al cure for HIV — one of the longest and most dif­fi­cult trails in drug R&D — us­ing a com­bo drug from Gilead.

While com­bi­na­tion ther­a­pies have long proven able to keep HIV locked in­to hid­den cel­lu­lar reser­voirs, elim­i­nat­ing those vi­ral pock­ets has proven to be dev­il­ish­ly dif­fi­cult. In a new an­i­mal study in­volv­ing rhe­sus mon­keys, though, re­searchers at Har­vard work­ing at Beth Is­rael Dea­coness Med­ical Cen­ter ad­vanced a lengthy ef­fort in pur­su­ing a “shock and kill” strat­e­gy us­ing a toll-like re­cep­tor com­bined with a killer an­ti­body.

Gilead’s ex­per­i­men­tal TLR7 ag­o­nist GS-9620 did the shock­ing, and the an­ti­body PGT121 did the killing. And while they weren’t able to erad­i­cate the reser­voirs, the re­searchers were able to do a good enough job to al­low close to half the mon­keys in the com­bo arm of the study to go with­out an­ti­retro­vi­ral for a lengthy stretch, rais­ing the promise that the same might be ac­com­plished in a large sub­set of hu­man pa­tients.

Dan Barouch

To test this ap­proach, in­ves­ti­ga­tors took 44 mon­keys in­fect­ed with a simi­an form of the virus and di­vid­ed them in­to 4 groups. They left one group in the place­bo arm, di­vid­ing the rest in­to two groups which were treat­ed with one of the two treat­ments alone and one group tak­ing a com­bi­na­tion. Then they took them off ther­a­py.

While the virus in most of the mon­keys in the place­bo or two monother­a­py arms quick­ly re­bound­ed, ready to kill as ever, 5 of the 11 pri­mates in the com­bo arm were able to go at least 168 days with­out re­bound­ing, with the oth­er 6 re­bound­ing but then able to sup­press the virus with­out an­ti­retro­vi­ral ther­a­py (ART).

Gilead has now ad­vanced the two treat­ments in Phase I stud­ies as they start to test how hu­mans will re­spond. Non­hu­man pri­mates have long been con­sid­ered an ide­al mod­el for an­tivi­ral ther­a­pies.

Why is this im­por­tant?

While pa­tients re­spond to longterm cock­tail ther­a­pies, they al­so ex­pe­ri­ence greater vul­ner­a­bil­i­ty to a va­ri­ety of mal­adies that can short­en their lives. The prospect of go­ing off ART for lengthy pe­ri­ods would hold the promise of sig­nif­i­cant­ly re­duc­ing those risks.

“New HIV ther­a­pies that aim to wake up and tar­get the vi­ral reser­voir have the po­ten­tial to play an im­por­tant role in long-term vi­ral sup­pres­sion with­out ART,” said Har­vard pro­fes­sor Dan Barouch, the di­rec­tor at the Cen­ter for Vi­rol­o­gy and Vac­cine Re­search, Beth Is­rael Dea­coness Med­ical Cen­ter.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

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No­vo Nordisk oral semaglu­tide tri­al shows re­duc­tion in blood sug­ar, plus weight loss

Novo Nordisk is testing higher levels of its oral version of its GLP-1, semaglutide, and its type 2 diabetes trial results released today show reductions in blood sugar as well as weight loss.

In the Phase IIIb trial, Novo compared its oral semaglutide in 25 mg and 50 mg doses with the 14 mg version that’s currently the maximum approved dose. The trial looked at how the doses compared when added to a stable dose of one to three oral antidiabetic medicines in people with type 2 diabetes who were in need of an intensified treatment.

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Ly­me vac­cine test com­ple­tion is pushed back by a year as Pfiz­er, Val­ne­va say they'll ad­just tri­al

Valneva and Pfizer have adjusted the end date for the Phase III study of their investigational Lyme disease vaccine, pushing it back by a year after issues at a contract researcher led to thousands of US patients being dropped from the test.

In a March 20 update to, Valneva and Pfizer moved the primary completion date on the trial, called VALOR, from the end of 2024 to the end of 2025.

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Stuart Peltz, former PTC Therapeutics CEO

Stu­art Peltz re­signs as PTC Ther­a­peu­tics CEO af­ter 25 years

Stuart Peltz, the longtime CEO of PTC Therapeutics who’s led the rare disease drug developer since its founding 25 years ago, is stepping down.

Succeeding him in the top job is Matthew Klein, who joined PTC in 2019 and was promoted to chief operating officer in 2022. In a call with analysts, he said the CEO transition has been planned for “quite some time” — in fact, as part of it, he gave the company’s presentation at the JP Morgan healthcare conference earlier this year.

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Bet­ter Ther­a­peu­tics cuts 35% of staff while await­ing dig­i­tal ther­a­peu­tic ap­proval

Digital therapeutics company Better Therapeutics announced on Thursday that it’s cutting 35% of its staff as it awaits FDA clearance for its first product.

The company, which launched eight years ago, is one of a growing group of companies seeking a digital alternative to traditional medicine. The space saw a record $7.5 billion in investments in 2021, according to Chris Dokomajilar at DealForma, with uses spanning ADHD, PTSD and other indications. However, private insurers have been slow to hop on board.

FDA spells out how can­cer drug de­vel­op­ers can use one tri­al for both ac­cel­er­at­ed and full ap­provals

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

Zhi Hong, Brii Biosciences CEO

Brii Bio­sciences stops man­u­fac­tur­ing Covid-19 an­ti­body com­bo, plans to with­draw EUA re­quest

Brii Biosciences said it will stop manufacturing its Covid-19 antibody combination, sold in China, and is working to withdraw its emergency use authorization request in the US, which it started in October 2021.

The Beijing and North Carolina biotech commercially launched the treatment in China last July but is now axing the work and reverting resources to other “high-priority programs,” per a Friday update. The focus now is namely hepatitis B viral infection, postpartum depression and major depressive disorders.

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FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

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