In a sur­prise set­back, Mer­ck has slammed the brakes on the de­vel­op­ment of an ex­per­i­men­tal HIV drug — in­clud­ing a Phase II tri­al — af­ter in­ves­ti­ga­tors flagged a drop in im­mune cell counts that an ex­ter­nal com­mit­tee de­ter­mined was re­lat­ed to treat­ment.

The Phase II study that first sound­ed the alarm, dubbed IMAG­INE-DR, was test­ing the once-week­ly com­bi­na­tion of MK-8507 (a non-nu­cle­o­side re­verse tran­scrip­tase in­hibitor) and is­la­travir, or ISL, a nu­cle­o­side re­verse tran­scrip­tase translo­ca­tion in­hibitor.

Where­as Mer­ck is paus­ing all pro­grams in­volv­ing MK-8507, the com­pa­ny says it “re­mains con­fi­dent in is­la­travir’s over­all pro­file” and will car­ry on with it.

For Mizuho an­a­lyst Mara Gold­stein, that of­fers a glass half full sit­u­a­tion.

“MRK’s lead an­ti-HIV can­di­date is is­la­travir (ISL), which we see as undis­turbed at this point,” she wrote. “Based on a larg­er body of clin­i­cal da­ta for ISL’s an­ti-HIV ef­fi­ca­cy in­clud­ing the re­cent pos­i­tive top-line up­date (see NOTE), we are not fore­cast­ing changes in the broad­er ISL-based HIV stud­ies, and our mod­el re­mains the same.”

Is­la­travir is al­so one of the two cen­ter­pieces of Mer­ck and Gilead’s joint ef­fort to de­vel­op a long-act­ing HIV ther­a­py, along­side Gilead’s cap­sid in­hibitor lenaca­pavir.

Joan But­ter­ton

Joan But­ter­ton, VP of in­fec­tious dis­eases glob­al clin­i­cal de­vel­op­ment at Mer­ck Re­search Lab­o­ra­to­ries, not­ed Mer­ck re­mains “res­olute” in its pledge to help end the HIV pan­dem­ic and high­light­ed that all clin­i­cal stud­ies pro­vide im­por­tant “learn­ings.”

In IMAG­INE-DR, study par­tic­i­pants ran­dom­ized to re­ceive ISL+MK-8507 saw a de­crease in to­tal lym­pho­cyte and CD4+ T cell counts. The great­est drops were ob­served in the arms of the study re­ceiv­ing the high­est dos­es of MK-8507, name­ly 200 mg and 400 mg.

The ex­ter­nal da­ta mon­i­tor­ing com­mit­tee con­clud­ed that the ad­verse ef­fect had to do with the treat­ment and rec­om­mend­ed stop­ping the tri­al. Mer­ck oblig­ed, and re­viewed all of its tri­als in­volv­ing ISL with a spe­cial eye to those met­rics.

Here’s what they found:

• The on­go­ing Phase II tri­al (MK-8591-016) is eval­u­at­ing month­ly ISL for PrEP in par­tic­i­pants with low risk of HIV-1 in­fec­tion. Among this un­in­fect­ed group, there was a dose-de­pen­dent de­crease in lym­pho­cyte counts but mean de­creas­es were in the nor­mal range, and there was no in­crease in clin­i­cal ad­verse events re­lat­ed to in­fec­tion.
• IL­LU­MI­NATE SWITCH A and IL­LU­MI­NATE SWITCH B (MK-8591A-017 and MK-8591A-018) are two Phase III tri­als eval­u­at­ing do­ravirine in com­bi­na­tion with ISL dai­ly (DOR/ISL) in HIV-1 vi­ro­log­i­cal­ly sup­pressed par­tic­i­pants. Here, Mer­ck found a small, treat­ment re­lat­ed mean de­crease in CD4+ T cell counts through week 48, but no in­creased in­ci­dence of AEs re­lat­ed to in­fec­tion.

Mer­ck re­cent­ly re­port­ed pos­i­tive da­ta from the IL­LU­MI­NATE stud­ies, sug­gest­ing the DOR/ISL com­bo has com­pa­ra­ble ef­fi­ca­cy as ex­ist­ing an­ti­retro­vi­ral ther­a­pies.

“In­ves­ti­ga­tors for these tri­als have been in­formed and the tri­als are con­tin­u­ing,” the com­pa­ny wrote.

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.