Pfiz­er ax­es a key Duchenne MD pro­gram af­ter PhII flop, rais­ing new doubts for a drug cat­e­go­ry that at­tract­ed Roche and Bio­gen

Pfiz­er is jet­ti­son­ing an­oth­er dis­ap­point­ing drug that’s been in the clin­ic for Duchenne mus­cu­lar dy­s­tro­phy. The phar­ma gi­ant says it’s ax­ing work on do­ma­grozum­ab (PF-06252616) — rais­ing the odds against one R&D fo­cus in the field that has at­tract­ed some mar­quee play­ers around the world.

The drug is one of sev­er­al de­signed to in­hib­it myo­statin, which flopped against a one-year test of mus­cle strength, fail­ing to help pa­tients to any sig­nif­i­cant de­gree. By sup­press­ing myo­statin, which blunts mus­cles, the the­o­ry is that a prop­er ther­a­py can help slow the mus­cle-wast­ing ail­ment that in­evitably proves fa­tal to the boys who in­her­it this dis­ease.

Seng Cheng

The fail­ure elim­i­nates one of sev­er­al an­ti-myo­statin ther­a­pies, in­clud­ing BMS-986089, a drug which Bris­tol-My­ers sold to Roche in the spring of 2017 for $170 mil­lion in cash and $205 mil­lion in mile­stones. That drug — now called RG6206 (RO7239361) — is in a Phase II/III study.

Just a month ago Bio­gen al­so got in­to the myo­statin game, pay­ing $27 mil­lion in cash to grab a Phase Ia drug called ALG-801 (BI­IB110) and a pre­clin­i­cal drug ALG-802 from Alive­G­en. Bio­gen not­ed at the time that the two drugs “rep­re­sent nov­el ways of tar­get­ing the myo­statin path­way, which is one of the most thor­ough­ly stud­ied ap­proach­es for mus­cle en­hance­ment.” These ther­a­pies are de­signed to tar­get the nys­tatin path­way, which Bio­gen be­lieves could work bet­ter than oth­er drugs in the clin­ic.

There’s noth­ing un­usu­al about fail­ure in this field, though, where Duchenne MD has proven a tough ob­jec­tive. No­var­tis ex­pe­ri­enced a late-stage set­back with their myo­statin drug bima­grum­ab (BYM338) in 2016. Atara–an Am­gen ($AMGN) spin­off–saw its clin­i­cal can­di­date PIN­TA 745 fail a Phase II study for pro­tein en­er­gy wast­ing in pa­tients with end-stage re­nal dis­ease, forc­ing the biotech to halt de­vel­op­ment ef­forts and switch fo­cus to can­cer. Back in 2011, Ac­celeron ($XL­RN) and Shire ($SH­PG) al­so halt­ed clin­i­cal work on ACE-031, an­oth­er myo­statin drug with big dreams in fight­ing mus­cle wast­ing, then de­cid­ed to scrap it al­to­geth­er in 2013 af­ter run­ning some ad­di­tion­al pre­clin­i­cal tests.

It’s just as bad in oth­er re­lat­ed mus­cle drug fields. Two months ago shares of Sum­mit were crushed in the wake of their failed Phase II for a utrophin mod­u­la­tor, ezutro­mid.

Duchenne MD has al­so been a mine field of con­tro­ver­sy in R&D. Sarep­ta gained an ap­proval for eteplirsen, with­out con­vinc­ing reg­u­la­tors it ac­tu­al­ly works. Now the biotech has been shift­ing at­ten­tion to its gene ther­a­py — put on hold re­cent­ly due to im­pu­ri­ties found in a third-par­ty pro­vid­ed plas­mid — which has looked promis­ing at the very ear­li­est stages of track­ing pa­tient re­spons­es. PTC, mean­while, has been pur­su­ing an FDA OK for ataluren, ap­proved in Eu­rope de­spite re­peat­ed fail­ures in the clin­ic. 

Not to be over­looked is Schol­ar Rock, where the ex­ec­u­tive team be­lieves they can find suc­cess by tar­get­ing la­tent rather than ac­tive myo­statin. The biotech, though, felt the heat Thurs­day morn­ing, with its shares plung­ing 12% on the news. That set­back trig­gered a flur­ry of de­fen­sive posts from an­a­lysts de­fend­ing Schol­ar Rock and bur­nish­ing their chances, with one less ri­val to wor­ry about.

Pfiz­er hasn’t quite giv­en up on its drug, leav­ing the door open to fu­ture tri­als in mus­cu­lar dis­eases. But its big re­main­ing ef­fort in DMD is in a gene ther­a­py pro­gram it has un­der­way for PF-06939926, an AAV de­liv­ered treat­ment which car­ries a short­ened ver­sion of the hu­man dy­s­trophin gene (mi­ni-dy­s­trophin).

“We are dis­ap­point­ed by these re­sults and while we are not pro­gress­ing with the stud­ies, the da­ta will con­tribute to a greater un­der­stand­ing of this dis­ease and we will eval­u­ate the to­tal da­ta set to see if there is a place for this med­i­cine in mus­cu­lar dis­eases,” said Seng Cheng, the CSO for the Pfiz­er Rare Dis­ease Re­search Unit.

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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