Buoyed by he­mo­phil­ia A gene ther­a­py up­date, Bio­Marin switch­es to head-to-head study -- but shares slide on dura­bil­i­ty con­cerns

With its he­mo­phil­ia A gene ther­a­py poised to go through a piv­otal pro­gram by the end of next year, Bio­Marin $BM­RN set out to boost hopes for its suc­cess with a new batch of Phase I/II da­ta for its val­rox pro­gram (val­oc­toco­gene rox­a­parvovec/BMN 270). But the biotech’s shares turned wob­bly and start­ed to slide on con­cerns that the new num­bers may have re­vealed some longterm weak­ness on ef­fi­ca­cy.

Hank Fuchs

Re­searchers at a con­fer­ence in Glas­gow are point­ing to one of the dosage arms where they tracked a 97% cut in an­nu­al­ized bleed­ing rate. And the biotech now plans to boost the num­ber of pa­tients in a reg­is­tra­tion study so they can pro­vide clear ev­i­dence of the gene ther­a­py’s abil­i­ty to beat the cur­rent stan­dard of care us­ing fac­tor re­place­ment ther­a­py.

The com­pa­ny will in­crease en­roll­ment by 90, tak­ing 130 pa­tients in­to the piv­otal pro­gram af­ter see­ing ev­i­dence of a durable abil­i­ty over 2 years to slash bleed rates in pa­tients..

“In or­der to make this op­tion avail­able with the ur­gency and da­ta sup­port that peo­ple with se­vere he­mo­phil­ia A de­serve, we plan to raise the sam­ple size of our reg­is­tra­tional study, Gen­er8-1 with the 6e13 dose to demon­strate ben­e­fits well be­yond pro­phy­lac­tic fac­tor use.” said Hank Fuchs, pres­i­dent, world­wide re­search and de­vel­op­ment at Bio­Marin.

The 6e13 vg/kg co­hort saw no spon­ta­neous bleeds and elim­i­na­tion of all bleeds in tar­get joints in the sec­ond year. And 71% and 86% of par­tic­i­pants had ze­ro bleeds re­quir­ing Fac­tor VI­II in­fu­sions in years 1 and 2 re­spec­tive­ly com­pared to 14% who had ze­ro bleeds re­quir­ing Fac­tor VI­II in­fu­sions for a year at base­line. There was a 96% re­duc­tion in mean FVI­II us­age through week 104. Qual­i­ty of life as mea­sured by the six-do­main Haemo-QoL-A in­stru­ment rapid­ly im­proved across all do­mains by up to 17.3 points in mean over base­line through the sec­ond year. 

Not­ed Bio­Marin: “This is well above the 5.2 point in­crease con­sid­ered to be the min­i­mal clin­i­cal­ly im­por­tant dif­fer­ence.”

An­a­lysts, though, high­light­ed some con­cerns with the ther­a­py’s abil­i­ty to keep fac­tor lev­els run­ning at a con­sis­tent lev­el, some­thing no gene ther­a­py de­vel­op­er wants to see. Leerink’s Joseph Schwartz picked out some sore points:

In the midst of to­day’s up­date, we be­lieve in­vestors will take is­sue with at least 2 points in the da­ta – 1) the grad­ual de­cline in FVI­II lev­els (breach­ing low­er bound of nor­mal on me­di­an FVI­II), and 2) Haemo-QoL gap down – gap up both be­fore and af­ter week 52. To the first point, mgmt. ref­er­enced pre­clin­i­cal ev­i­dence as well as the bi­ol­o­gy of gene ex­pres­sion to sug­gest a sta­ble plateau may have been achieved. Up­on fur­ther ob­ser­va­tion, it ap­pears the ma­jor gap down oc­curred be­tween weeks 78 and 91 lead­ing to the ma­jor­i­ty of pts. ex­hibit­ing nor­mal lev­els of FVI­II (50-150 IU/dL) by week 104. It is not ex­act­ly clear what trig­gered the drop, or whether this de­crease was an anom­aly (e.g., dri­ven by 1-2 pts.); how­ev­er, we would ex­pect to see con­tin­ued per­sis­tence of ~50 IU/dL lev­el in sub­se­quent up­dates po­ten­tial­ly at the Amer­i­can So­ci­ety of Hema­tol­ogy (ASH) by YE18. As for the sud­den drop in Haemo-QoL, mgmt. clar­i­fied that the week 52-78 dy­nam­ic was dri­ven by ex­tra­or­di­nary cir­cum­stances in 1 pt. (in­clud­ing job loss and a pre-planned knee re­place­ment). Over­all, dri­ven by a broad im­pact (i.e., across all six do­mains of the as­sess­ment), mgmt. is op­ti­mistic that the pos­i­tive ef­fects seen across clin­i­cal end­points are al­so ben­e­fit­ing pt. QoL.

Bio­Marin’s shares slid 4% mid-day on the wor­ries.

Bio­Marin has high hopes for this ther­a­py, a bell­wether treat­ment in a mix of drugs be­ing po­si­tioned to take the he­mo­phil­ia mar­ket by storm. Its progress on he­mo­phil­ia A comes a year af­ter Pfiz­er struck a pricey deal with Sang­amo to use its zinc fin­ger tech to make a ri­val — though Bio­Marin re­mains well in front. The Sang­amo team dosed their first pa­tient last fall, while Bio­Marin has two years of da­ta on some pa­tients.

In the mean­time, Bio­Marin is wait­ing out the clock on its May 25 PDU­FA dead­line for peg­valiase, which it hopes will soon be­come its 7th mar­ket­ed drug.


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


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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