JJ Bienaimé, BioMarin CEO (Via YouTube)

New da­ta show Bio­Mar­in's trou­bled he­mo­phil­ia gene ther­a­py con­tin­ues to fade, open­ing room for ri­vals

The ef­fects of Bio­Marin’s vaunt­ed gene ther­a­py for he­mo­phil­ia A are con­tin­u­ing to fade in the ear­li­est treat­ed pa­tients, re­new­ing ques­tions about the long-term prospects for a drug the com­pa­ny had billed as a one-time cure.

At the In­ter­na­tion­al So­ci­ety on Throm­bo­sis and Haemosta­sis meet­ing Wednes­day, Bio­Marin an­nounced that, af­ter five years, the first sev­en pa­tients treat­ed with the ther­a­py’s high dose ex­pressed a me­di­an of just 8.2% the amount of fac­tor VI­II that a healthy per­son would. That’s a small frac­tion of the 60.3% ex­pres­sion pa­tients saw one year af­ter re­ceiv­ing the ther­a­py, known as val­rox.

Bio­Marin high­light­ed — as they have be­fore — that de­spite the wan­ing lev­els of pro­tein, pa­tients were still large­ly symp­tom-free. The ther­a­py re­duced the an­nu­al­ized bleed­ing rate by 95% among six of the pa­tients, and even in year 5, six of the sev­en pa­tients had no bleed­ing events at all.

He­mo­phil­ia A pa­tients are miss­ing a func­tion­al copy Fac­tor VI­II, a clot­ting pro­tein es­sen­tial for stop­ping bleed­ing. But as with sick­le cell and many ge­net­ic dis­eases now be­ing tar­get­ed by gene ther­a­pies, re­searchers don’t ac­tu­al­ly have to get pa­tients to com­plete nor­mal ex­pres­sion in or­der to al­le­vi­ate symp­toms and al­low peo­ple to lead healthy lives; of­ten a frac­tion will do.

Pre­cise­ly how large a frac­tion, though, re­mains un­known, and Bio­Marin’s dwin­dling lev­els have raised flags with reg­u­la­tors. Last year, in a sur­prise move, the FDA re­ject­ed the com­pa­ny’s ap­pli­ca­tion for ap­proval, say­ing they would need to see more dura­bil­i­ty da­ta be­fore al­low­ing Bio­Marin to put the drug on the mar­ket.

Dura­bil­i­ty is a greater con­cern with mod­ern gene ther­a­pies than it is for oth­er med­i­cines. Pa­tients can on­ly be dosed once, giv­ing re­searchers on­ly a sin­gle shot to cure the dis­ease. And the com­pa­ny’s CEO JJ Bi­en­aimé has promised to price val­rox as if it were a cure: be­tween $2 mil­lion and $3 mil­lion per year.

The new da­ta, though, show that gene ex­pres­sion has steadi­ly de­clined year-to-year, un­der­scor­ing con­cerns that it could one day drop be­low lev­els that are ther­a­peu­ti­cal­ly rel­e­vant and keep pa­tients off of trans­fu­sions.

Those fears may not pre­vent Bio­Marin from ob­tain­ing ap­proval. The com­pa­ny ex­pects to have two-year da­ta from its Phase III tri­al in ear­ly 2022, at which point they would like­ly re­file with the FDA.

It could, how­ev­er, dras­ti­cal­ly di­min­ish the ther­a­py’s ben­e­fit for pa­tients and how much mon­ey Bio­Marin can make. With oth­er he­mo­phil­ia A gene ther­a­pies al­so near­ing ap­proval, pa­tients may wait for some­thing that looks clos­er to a one-time cure.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

UK re-in­ves­ti­gates Pfiz­er's eye-pop­ping price goug­ing on an epilep­sy drug

When a drugmaker raises the price of a drug in the US by more than 2,000% overnight, and without any particular reason for that increase, nothing typically happens to the company. No fines, no court orders, just business as usual.

Martin Shkreli’s decades-old anti-parasitic drug Daraprim was the perfect example — massive price spike on an old drug, lots of media attention, public outcry, Congressional committees dragging his former company through multiple hearings, and at the end of it? Nothing happened to the price or the company (until generic competition came).

Marianne De Backer (L) and Jeff Hatfield

Bay­er nabs star biotech Vi­vid­ion with a $2B buy­out and an ‘arms-length’ pact, pulling a part­ner out of the IPO con­ga line

Vividion is canceling that IPO it filed. Instead of following the industry-wide migration to Nasdaq, the biotech that has captured considerable attention for its still-preclinical work finding cryptic pockets to bind to on proteins is going to work for Bayer now.

The pharma giant is putting out word today that it has bought out Vividion for $1.5 billion in cash and another half-billion dollars in milestones.

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Josh Hoffman, outgoing Zymergen CEO (Zymergen)

UP­DAT­ED: Syn­bio uni­corn Zymer­gen jet­ti­sons found­ing CEO, cuts guid­ance as cus­tomers re­port lead prod­uct does­n't work

Zymergen, just months off a $500 million IPO that put the synthetic bio firm in rarified air, has now ejected its founding CEO and downgraded its revenue forecasts after customers reported its lead film product doesn’t work as advertised, the company said Tuesday afternoon.

CEO Josh Hoffman will leave his role and sacrifice his board seat immediately in favor of Jay Flatley, the former CEO of Illumina who will take the lead role on an interim basis as the company conducts a search for its next leader.

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Tadataka Yamada (Photographer: Kiyoshi Ota/Bloomberg via Getty Images)

Sci­ence pi­o­neer, phar­ma re­search chief, glob­al health ad­vo­cate and biotech en­tre­pre­neur Tadata­ka ‘Tachi’ Ya­ma­da has died

Tadataka Yamada, a towering physician-scientist who made his name in academia before transforming drug development at GlaxoSmithKline and developing vaccines for malaria and meningitis at the Gates Foundation, died unexpectedly of natural causes at his home in Seattle Wednesday morning.

He was 76. Frazier Healthcare Partners’ David Socks confirmed his death.

Known widely by the mononym “Tachi,” Yamada had a globetrotting career and arrived in industry relatively late in life. A 2004 Independent article noted GSK had asked Yamada to stay on beyond his approaching 60th birthday, the company’s usual retirement age. Yamada would continue working for the next 17 years, steering the Gates Foundation’s global health division for 6 years, funding Jim Wilson’s gene therapy work when few would touch it, launching Takeda Vaccines and co-founding a series of high-profile biotechs.

Thomas Lingelbach, Valneva CEO

A small vac­cine de­vel­op­er fa­vored by the UK gov­ern­ment in Covid-19 touts a PhI­II first in chikun­gun­ya

Before Valneva garnered the favor of the UK government as a potential supplier of Covid-19 vaccines, the French biotech prided itself on being the first company to bring a chikungunya vaccine into Phase III.

It now has positive pivotal results to back up the breakthrough therapy designation the FDA granted just weeks ago.

There are currently no approved jabs to prevent chikungunya virus infection despite decades of R&D efforts, a fact that underscores just how arduous traditional vaccine development can be, particularly for neglected tropical disease. In a absence of a major commercial market, the US government and NGOs such as CEPI have deployed various grants and incentives to spur on a small crew of academics and industry players, with Merck, via its acquisition of Themis, claiming a spot in that race.

Zymergen co-founders Zach Serber, Josh Hoffman, and Jed Dean (Zymergen via website)

Zymer­gen's sud­den im­plo­sion shocked biotech. A lin­ger­ing loan could make things even worse

As former synbio unicorn Zymergen picks up the pieces from its spectacular implosion Tuesday, an outstanding loan from Perceptive Advisors — the only blue-chip biotech crossover investor to touch Zymergen’s fundraising efforts — could make the situation worse, according to public documents.

In December 2019, more than a year before Zymergen filed for what would eventually become a $500 million IPO, the “biofacturing” firm signed a $100 million credit facility with Perceptive to help supplement the nearly $700 million the company had raised across four VC rounds.

Lan Huang, BeyondSpring CEO

Shares of Be­yond­Spring sky­rock­et on new, pos­i­tive can­cer drug tri­al re­sults

Sometimes results come along that shock even a biotech’s believers.

On Wednesday, BeyondSpring, a small New York biotech with an offbeat approach to immunotherapy, announced its lead drug significantly extended non-small cell lung cancer patients’ lives in a large trial. Although the company did not release the exact survival data, it said that nearly twice as many patients were alive after two years on the drug arm than on the standard-of-care arm.

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Pfiz­er puts the pres­sure on Eli Lil­ly's JAK in­hibitor Olu­mi­ant with new da­ta in alope­cia area­ta

As Eli Lilly looks to secure a win for its blockbuster Olumiant in alopecia areata, going where no JAK inhibitor has gone before, Pfizer is coming up from behind with Phase IIb/III results suggesting its own candidate can help regrow hair lost due to the autoimmune disease.

On Wednesday, Pfizer unveiled topline results from the ALLEGRO trial, which enrolled 718 patients 12 years and older with alopecia areata, a condition that can cause sudden, severe and patchy hair loss. While the patients’ episodes of alopecia areata varied in length, they all had one thing in common: They had lost at least half the hair on their scalps.