Roger Perlmutter, Merck

Catch­ing up with Roche, Mer­ck racks up pos­i­tive da­ta in front­line triple neg­a­tive breast can­cer

Mer­ck’s Keytru­da may not have qual­i­fied as a sec­ond- or third-line treat­ment of triple neg­a­tive breast can­cer, but the PD-1 in­hibitor is show­ing promise for the first-line set­ting in a Phase III tri­al.

In­ves­ti­ga­tors for the KEYNOTE-355 study re­port that Keytru­da plus chemother­a­py sig­nif­i­cant­ly im­proved pro­gres­sion-free sur­vival for pa­tients with metasta­t­ic TNBC whose tu­mors ex­press PD-L1 com­pared to chemo alone, hit­ting a co-pri­ma­ry end­point.

The topline re­sult was from an in­ter­im analy­sis. The oth­er pri­ma­ry end­point, over­all sur­vival, is still be­ing eval­u­at­ed.

Front­line triple neg­a­tive breast can­cer — a par­tic­u­lar­ly hard to treat form of the dis­ease that ac­counts for 10% to 20% of all breast can­cer cas­es — is one of the rare fields in which Roche’s PD-L1 Tecen­triq has en­joyed a head start over Keytru­da and Op­di­vo, the lead­ers in the check­point race. Tecen­triq is ap­proved in com­bi­na­tion with Abrax­ane for this in­di­ca­tion.

It didn’t help when Mer­ck con­ced­ed fail­ure in KEYNOTE-119, where Keytru­da failed to help pre­vi­ous­ly treat­ed pa­tients live longer.

But things soon took a turn for the bet­ter, as the com­pa­ny found that a neoad­ju­vant reg­i­men of Keytru­da and chemo — fol­lowed by Keytru­da monother­a­py af­ter surgery — in­duced a high­er patho­log­i­cal com­plete re­sponse rate. The con­trol arm, which re­ceived chemo alone, saw a pCR of 51.2% ver­sus 64.8% for the Keytru­da group.

That’s a key mark­er for pro­gres­sion and re­cur­rence, ex­ecs said.

But SVB Leerink an­a­lysts are less op­ti­mistic. In a note, Daina Gray­bosch point­ed out that the tri­al had six pri­ma­ry end­points, not all of which ap­peared to have been met. On­ly pa­tients with PD-L1 Com­bined Pos­i­tive Score (CPS) ≥ 10 ben­e­fit­ed, but not those whose CPS was high­er than or equal to 1.

Though they re­port­ed pos­i­tive topline da­ta for Keytru­da (pem­brolizum­ab) with chemother­a­py in PD-L1 high pa­tients, the reg­i­men failed to show ben­e­fit in a broad­er TNBC pop­u­la­tion. By the time Mer­ck en­ters the mar­ket, Roche will have a two-year lead, in ad­di­tion to a more pre­dic­tive bio­mark­er for clin­i­cal ben­e­fit (im­mune-cell (IC) PD-L1). A launch for Keytru­da in neo-ad­ju­vant TNBC would mit­i­gate this mar­ket risk, but we do not ex­pect this un­til 2021 at the ear­li­est, await­ing more ma­ture dis­ease-free sur­vival da­ta.

Roger Perl­mut­ter, who over­sees Keytru­da’s ex­pan­sive de­vel­op­ment pro­gram, high­light­ed that tri­al — KEYNOTE-522 — to­geth­er with the new Phase III as he talked up the po­ten­tial of reg­is­tra­tion.

While tar­get­ed ther­a­pies have ben­e­fit­ed a num­ber of breast can­cer pa­tients, the fact that TNBC is nei­ther fu­eled by the hor­mones es­tro­gen and prog­es­terone nor by the HER2 pro­tein ren­ders it es­pe­cial­ly hard to treat.

“While de­tail da­ta has yet to be an­nounced, a PFS hit in this pop­u­la­tion is im­por­tant giv­en the lack of avail­able ther­a­pies in this dis­ease, and fur­ther in­di­cates a role of check­point in­hibitors in a sub­set (of) TNBC pa­tients,” Mara Gold­stein of Mizuho not­ed about KEYNOTE-355.

Roche is look­ing to ex­pand its suc­cess with the Tecen­triq and Abrax­ane reg­i­men by adding their PI3K/AKT path­way drug ipatasert­ib to the mix — with some en­cour­ag­ing ear­ly da­ta.

Oth­er small­er play­ers have ze­roed in on new tar­gets, such as pro­tein ki­nase C, Lipocalin 2 and CD24.

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.

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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Sanofi, Re­gen­eron boast PhI­II win with Dupix­ent in COPD, clear­ing first bar for ex­pan­sion

Dupixent, the blockbuster anti-inflammatory drug from Sanofi and Regeneron, has cleared a high-stakes Phase III study in chronic obstructive pulmonary disease, the companies announced Thursday morning.

If they hold up in a second, identical trial, the data pave the way for Dupixent to become the first biologic to treat patients whose COPD remains uncontrolled despite being on maximal standard-of-care inhaled therapy — the patient population studied in the pivotal program. The companies had spotlighted this as a key readout as they look to expand the Dupixent franchise and explore its full potential.

Chat­G­PT with phar­ma da­ta de­buts for med­ical meet­ings, be­gin­ning with AACR

What do you get when you combine ChatGPT generative AI technology with specific pharma and clinical datasets? A time-saving tool that can answer questions about medical conference abstracts and clinical findings in seconds in one new application from ZoomRx called FermaGPT.

ZoomRx is debuting a public version of its generative AI product specifically for medical conferences beginning this week for the upcoming American Association for Cancer Research (AACR) annual meeting that runs April 14-19.

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Alaa Halawa, executive director at Mubadala’s US venture group

The ven­ture crew at Mubadala are up­ping their biotech cre­ation game, tak­ing care­ful aim at a new fron­tier in drug de­vel­op­ment

It started with a cup of coffee and a slow burning desire to go early and long in the biotech creation business.

Wrapping up a 15-year discovery stint at Genentech back in the summer of 2021, Rami Hannoush was treated to a caffeine-fueled review of the latest work UCSF’s Jim Wells had been doing on protein degradation — one of the hottest fields in drug development.

“Jim and I have known each other for the past 15 years through Genentech collaborations. We met over coffee, and he was telling me about this concept of the company that he was thinking of,” says Hannoush. “And I got immediately intrigued by it because I knew that this could open up a big space in terms of adding a new modality in drug discovery that is desperately needed in pharma.”

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FDA re­jects Ab­b­Vie's in­fu­sion ther­a­py for Parkin­son's, re­quests more in­fo on pump de­vice

The FDA rejected AbbVie’s 24-hour infusion therapy for Parkinson’s, saying it needs more information on a device used to administer the treatment before it can clear it.

The Chicago-area drugmaker said in a press release that the complete response letter from the agency didn’t include any requests for more efficacy or safety trials related to the drug, known as ABBV-951. The company said it aims to “resubmit the NDA as soon as possible.”

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Genen­tech to stop com­mer­cial man­u­fac­tur­ing at Cal­i­for­nia head­quar­ters

Genentech is halting commercial manufacturing at its California headquarters — and laying off several hundred employees.

The move is the result of a decision Genentech made in 2007 to relocate manufacturing operations from its South San Francisco headquarters location to other facilities or move the work to CDMOs, said Andi Goddard, Genentech’s SVP of quality and compliance for pharmaceutical technical operations, in an interview with Endpoints News. Genentech has made changes in capabilities and invested more in technology, so it doesn’t need as many large-scale manufacturing facilities as it did in the past, she said.

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In­cyte wins ac­cel­er­at­ed ap­proval for PD-1 in rare skin can­cer

Incyte touted an accelerated approval for its PD-1 retifanlimab in a rare skin cancer on Wednesday, roughly a year and a half after the drug suffered a rejection in squamous cell carcinoma of the anal canal (SCAC).

Retifanlimab, marketed as Zynyz, was approved for metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), a fast-growing skin cancer typically characterized by a single, painless nodule. It’s roughly 40 times rarer than melanoma, according to the nonprofit Skin Cancer Foundation — but incidence is growing, particularly among older adults, Incyte said in its announcement.

A new study finds that many patient influencers are sharing prescription drug experiences along with health information.

So­cial me­dia pa­tient in­flu­encers ‘danc­ing in the gray’ of phar­ma mar­ket­ing, more clar­i­ty need­ed, re­searcher says

It’s no surprise that patient influencers are talking about their health conditions on social media. However, what’s less clear is what role pharma companies are playing, how big the patient influencer industry is, and just how is information about prescription drugs from influencers relayed — and received — on social media.

While University of Colorado associate professor Erin Willis can’t answer all those questions, she’s been researching the issue for several years and recently published new research digging into the communication styles, strategies and thinking of patient influencers, many of whom partner with pharma companies.

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