Joan Butterton, Merck Research Laboratories VP of global clinical development, infectious diseases (Merck)

Mer­ck­'s ex­per­i­men­tal HIV drug is­la­travir hits with a PhI­II com­bo win and FDA fil­ing plans

Back in March, Mer­ck and Gilead agreed to a part­ner­ship to chal­lenge Glax­o­SmithK­line on long-act­ing HIV meds — by com­bin­ing one drug from both Mer­ck and Gilead that had shown po­ten­tial. While Gilead brought its cap­sid in­hibitor lenaca­pavir, Mer­ck brought is­la­travir in­to the deal — a small mol­e­cule that the phar­ma ac­quired in 2012 from a small Japan­ese firm.

While that part­ner­ship is on­go­ing, is­la­travir is com­ing out of 2 Phase III piv­otal tri­als with back-to-back suc­cess­es and plans to beat a quick ad­vance to the FDA.

The phar­ma gi­ant re­vealed top-line re­sults this morn­ing from its piv­otal Phase III tri­als of a once-dai­ly oral pill com­bin­ing Mer­ck’s FDA-ap­proved an­ti-HIV treat­ment Pifel­tro with is­la­travir. The par­tic­i­pants, who are adults with HIV-1 in­fec­tion who are on two dif­fer­ent an­ti­retro­vi­ral ther­a­py pro­to­cols, in­clud­ing a bicte­gravir/emtric­itabine/teno­fovir triple, were com­pared at 48 weeks.

Mer­ck has main­tained a steady run­ner-up rep in HIV, a field dom­i­nat­ed by Gilead and then Vi­iV, ma­jor­i­ty owned by GSK. And no mat­ter what hap­pens with the Mer­ck com­bo now that it’s head­ed to reg­u­la­tors, an­a­lysts don’t ex­pect any­thing to beat out Gilead’s mar­ket leader. A few months ago Bern­stein’s Ron­ny Gal as­sessed the al­liance be­tween Mer­ck and Gilead, con­clud­ing:

For HIV treat­ment it will be hard to un­seat Bik­tarvy. HIV treat­ments have ef­fec­tive­ly reached the up­per-lim­it on ef­fi­ca­cy and tol­er­a­bil­i­ty. From here, new prod­ucts will try to dif­fer­en­ti­ate based on qual­i­ty-of-life en­hance­ments like less fre­quent dos­ing and low­er as­so­ci­at­ed weight gain. These val­ue propo­si­tions are re­al, but pa­tient turnover in HIV is rel­a­tive­ly low and we be­lieve it would a tough sell to switch vi­ral­ly sup­pressed pa­tients of Bik­tarvy. As a re­sult, we mod­el on­ly 30% peak mar­ket share for ISL/LEN com­bi­na­tions – ma­te­r­i­al, but less than Bik­tarvy.

Both of the Mer­ck tri­als met their pri­ma­ry end­point on the per­cent­age of par­tic­i­pants with HIV-1 RNA lev­els at or be­low 50 copies/mL — show­ing that an­tivi­ral ef­fi­ca­cy was com­pa­ra­ble be­tween the drug com­bo and an­ti­retro­vi­ral ther­a­pies, ac­cord­ing to a com­pa­ny state­ment.

For ref­er­ence, any lev­el of HIV-1 RNA be­low 50 copies/mL is con­sid­ered op­ti­mal for pa­tients — some­times that num­ber is con­sid­ered un­de­tectable in a blood test. A “low­er vi­ral load” is any num­ber be­low 10,000 copies/mL — and a high vi­ral load is con­sid­ered to be any­where from 100,000 to a mil­lion copies of RNA/per mL of blood.

The safe­ty and tol­er­a­bil­i­ty of the com­bi­na­tion drug were con­sis­tent with da­ta from Phase II stud­ies, ac­cord­ing to Mer­ck — and these re­sults will lead the way for “glob­al reg­u­la­to­ry ap­pli­ca­tions.”

“We are en­cour­aged by the re­sults from the Phase 3 IL­LU­MI­NATE SWITCH A and B tri­als, in which the DOR/ISL dual reg­i­men ef­fi­ca­cy was com­pa­ra­ble to cer­tain com­mon­ly used three-drug reg­i­mens,” said Joan But­ter­ton, VP of glob­al clin­i­cal de­vel­op­ment, in­fec­tious dis­eases at Mer­ck Re­search Lab­o­ra­to­ries. “We will con­tin­ue to study do­ravirine/is­la­travir in di­verse pop­u­la­tions of peo­ple liv­ing with HIV and look for­ward to shar­ing da­ta from these tri­als.”

Spe­cial re­port: Meet 20 ex­tra­or­di­nary women who are su­per­charg­ing bio­phar­ma R&D

Even though many biopharma leaders have come together in recent years to address its gender gap, the consensus is clear: We still have a long way to go.

Companies this year were 2.5 times more likely than last year to have a diversity and inclusion program in place, according to a recent BIO survey, but women are still largely absent from executive roles. Getting women to enter the industry isn’t the problem — studies show that they represent just under half of all biotech employees around the world. But climbing through the ranks can be challenging, as women still report facing stereotypes, and, unfortunately, harassment.

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Op­ti­miz­ing Oral Drug De­liv­ery us­ing Zy­dis® Oral­ly Dis­in­te­grat­ing Tablet Tech­nol­o­gy to Ad­dress Pa­tient Chal­lenges

KEY POINTS

Patients prefer oral dosing, but swallowing tablets can be a challenge for many patients.
The Zydis® orally disintegrating tablet (ODT) platform addresses challenges associated with oral dosing, expanding benefits for patients and options for healthcare providers.
A strong growth trajectory is expected for ODTs given therapeutic innovation and continued technology development.

Many patients prefer conventional tablets for the administration of medications, but some geriatric and pediatric patients and those with altered mental status and physical impairments find swallowing tablets to be difficult. Orally disintegrating tablets (ODTs), which dissolve completely without chewing or sucking, offer a patient-friendly dosage form for the administration of small-molecule drugs, peptides and proteins. With the potential for multiple sites of drug absorption, often faster onset action for the active pharmaceutical ingredient (API), and potentially greater bioavailability, ODTs are an attractive option for drug developers considering first-to-market formulations or product line extensions of existing drugs with compatible API. In this report, we look at how innovation in the industry-leading Zydis ODT platform is expanding oral formulation options and bringing benefits to patients.

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Geoffrey Porges (SVB Leerink)

The 2022 wave com­ing? Top an­a­lyst says Big Phar­ma will have more than $1T avail­able to sat­is­fy its grow­ing ap­petite for biotech M&A

All through this year you could practically feel the frustration of the biotech investor class as M&A activity continued to drag behind expectations — or desires. Buyouts of public companies provide the essential juice for keeping stocks lively, and there’s been a notable lack of juice in 2021.

So is all that about to change, big time?

SVB Leerink’s Geoffrey Porges, a longtime student of biotech M&A, thinks so. In a lengthy analysis he put out last week, Porges totted up the cash flow of the major pharmas and determined that there was a good long list of industry buyers who would have around a half trillion dollars of cash to play with in 2022. Leverage that up with added debt and you could get that deal cache to $1.6 trillion.

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Mer­ck pumps the brakes on two more PhI­II tri­als for its lead an­ti-HIV drug

After trial investigators flagged a drop in immune cell counts that an external committee determined was related to treatment last month, Merck has been pausing HIV-related Phase II and III trials ever since.

On Monday, the biopharma company announced it’s pausing enrollment in two of its Phase III trials evaluating its leading anti-HIV drug candidate, which is the once-monthly, oral islatravir.

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Bolt Bio CEO Randy Schatzman

Bolt Bio goes bust as in­vestors boo sin­gle re­sponse in ear­ly test against HER2-ex­press­ing tu­mors

Bolt Bio’s BDC-1001, an antibody conjugate drug designed to amp up the body’s innate immune system response to tumors, posted a single partial response in a Phase I/II study in patients with HER2-expressing solid tumors after a year of dosing. Just 13 of 40 evaluable patients showed any signs of “clinical activity,” the biotech said Monday.

BDC-1001 links a HER2-targeting biosimilar of Herceptin with a TLR7/8 agonist, which is designed to activate myeloid cells in the innate immune system and drive tumor cytotoxicity, Bolt said. But the early results paint the picture of a drug with little effect on HER2 tumors, one of the most highly validated tumor targets in drug development.

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Biohaven CEO Vlad Coric (Photo Credit_ Andrew Venditti)

Bio­haven shakes up lead­er­ship team as it feels the heat from mi­graine com­peti­tors

As Biohaven Pharma comes off a rollercoaster pipeline year, its CEO will take on more responsibility in a full C-suite makeover.

Vlad Coric was unanimously elected to the role of chairman of the board of directors, after Declan Doogan’s retirement. Matthew Buten will take over the role of CFO after James Engelhart’s retirement, and director Michael Heffernan has been appointed lead independent director. All of the appointments are effective immediately, a company press release said.

Chen Schor, Adicet CEO

Adicet un­veils ear­ly re­spons­es for off-the-shelf drug lever­ag­ing rare T cells. Will dura­bil­i­ty hold up?

On the hunt for the next generation of “off-the-shelf” cell therapies, biotech players like Adicet Bio have looked to leverage some of the less-obvious members of the immune system as potent cancer fighters. In Adicet’s case, scarce gamma delta T cells are on the menu, and an early cut of data is showing some promise.

Adicet’s AD-001, an off-the-shelf cell therapy developed by engineering a CD20-targeting chimeric antigen receptor (CAR) onto a donor’s gamma delta T cells, posted two complete responses across four patients in an early Phase I study testing the drug in patients with heavily pretreated B cell non-Hodgkin’s lymphoma, the biotech said Monday.

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Mar­ket­ingRx Matchup: How Ab­b­Vie and Bio­haven ads rank in head-to-head mi­graine chal­lenge

Are you ready to rumble? DTC brands that is. MarketingRx is launching a new monthly feature today called MarketingRx Matchup. We’re pitting two pharma brands’ DTC advertising in the same therapeutic category against each other to find out what consumers and patients really think.

Market research company Leger is handling the polling and analysis each month, and I’ll be writing up the results — along with my own take — inside MRx on the first Tuesday of the month.

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Wendy Lund, Organon chief communications officer

Q&A: Organon chief com­mu­ni­ca­tions of­fi­cer Wendy Lund talks about the Mer­ck spin­off, women’s health and why it mat­ters

One of Wendy Lund’s earliest jobs was head of marketing at Planned Parenthood. As the youngest person on its management team, she introduced them to emerging new technologies, and in return, she learned the importance of fighting for what you believe in.

Now as chief communications officer at Organon, the women’s health company recently spun off by Merck, Lund is keeping that point top of mind. That’s in part because women’s health hasn’t been a spotlight therapy area for Big Pharma in years. Several companies have spun off, sold or at least considered selling women’s health assets to focus on “core” products.

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