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.

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.

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.