Al­ny­lam spot­lights just how good the ef­fi­ca­cy da­ta are for givosir­an — tamp­ing down on safe­ty con­cerns

Al­ny­lam $AL­NY took an­oth­er turn on its tran­si­tion lap to a ful­ly fledged com­mer­cial biotech to­day, post­ing its de­tailed — and very promis­ing — ef­fi­ca­cy da­ta for their RNAi drug givosir­an while hop­ing to tamp down the fret­ting over safe­ty is­sues that spoiled their ear­li­er top-line an­nounce­ment.

We knew go­ing in­to the Eu­ro­pean As­so­ci­a­tion for the Study of the Liv­er meet­ing in Vi­en­na that the drug had a great p val­ue — now backed up by a 90% me­di­an re­duc­tion in at­tacks of acute he­pat­ic por­phyr­ia, a painful and de­bil­i­tat­ing ill­ness with no cur­rent­ly ap­proved ther­a­pies. Half of the pa­tients end­ed at­tack free, which would make this a no-brain­er for reg­u­la­tors.

What rat­tled some of the an­a­lysts last time was that the rate of se­ri­ous ad­verse events in the drug arm was more than twice what was seen in the place­bo group. A se­ri­ous safe­ty sig­nal could ham­per or tor­pe­do any drug, and in­deed we learned that sev­er­al of the pa­tients ex­pe­ri­enced se­ri­ous is­sues trig­gered by the ther­a­py. Specif­i­cal­ly, this in­volved cas­es of chron­ic kid­ney dis­ease, pyrex­ia and ab­nor­mal liv­er func­tion test.

Al­ny­lam CEO John Maraganore, though, says that with this drug for this dis­ease in these pa­tients, it will pass muster to soon be­come Al­ny­lam’s sec­ond ap­proved ther­a­py — a land­mark event for a com­pa­ny that has be­come a stan­dard-set­ter for many of the de­vel­op­ment-stage com­pa­nies hop­ing to tran­si­tion in­to mar­ket­ing one day.

Al­ny­lam CEO John Maraganore Get­ty Im­ages

Click on the im­age to see the full-sized ver­sion

“This is a dis­ease that’s about as bad as it gets,” Maraganore told me in a pre­view of to­day’s pre­sen­ta­tion. “It is a ter­ri­ble, ter­ri­ble dis­ease, and ob­vi­ous­ly when you look at the ben­e­fit it’s pret­ty over­whelm­ing.”

Maraganore knows that 2 cas­es of CKD won’t go un­no­ticed by any­one, but in bal­anc­ing the risk/ben­e­fit, he says there’s no doubt that the drug will get a green light. Be­sides, he adds, these pa­tients typ­i­cal­ly have a high risk of kid­ney dis­ease and liv­er is­sues, which reg­u­la­tors will cer­tain­ly take in­to ac­count.

As for pa­tients, he says, the da­ta speak for them­selves, with 93 of 94 pa­tients go­ing on to en­roll in the ex­ten­sion pe­ri­od of the study.

“We couldn’t be more hap­py about the da­ta,” he adds. “If my daugh­ter had this dis­ease I wouldn’t hes­i­tate for a nanosec­ond” to get her on the drug. And then he threw his moth­er and him­self in­to that sce­nario. 

Every­body gets the drug.

That has Jef­feries? Mau­ry Ray­croft fore­cast­ing $600 mil­lion in peak sales by 2030. He adds:

For us, there were no sur­pris­es at EASL, and as a re­sult we are more con­fi­dent in gi­vo’s over­all pro­file and po­ten­tial. The ph.III in­ves­ti­ga­tor and AL­NY be­lieve the drug can be used broad­ly in AHP; add’ly, both AL­NY and the in­ves­ti­ga­tor an­tic­i­pate re­sults will con­tin­ue to im­prove.

Some of the ob­servers ear­li­er al­so weren’t too hap­py about a mixed set of sec­ondary end­points, with the ther­a­py scor­ing for sev­er­al bio­mark­ers of the dis­ease but falling short of sta­tis­ti­cal sig­nif­i­cance on sec­on­daries like pain and fa­tigue and nau­sea, what pa­tients are feel­ing.

Maraganore con­ced­ed those points but coun­tered that you don’t have to hit every sec­ondary to get an ap­proval — true enough — and that a set of pa­tient-re­port­ed out­comes in­di­cat­ed that 89% re­port­ed an im­prove­ment on ther­a­py com­pared to 37% on place­bo.

Maraganore is like­ly right about the caveats. No ther­a­py is per­fect, and reg­u­la­tors will bend over back­wards on side ef­fects if they can get a treat­ment for this dis­ease. That leaves Al­ny­lam com­ing out of EASL with a time­line that an­tic­i­pates an ap­proval by this time next year.

As of now, they’re odds-on fa­vorites for an ap­proval.

Im­age: Kristof­fer Trip­plaar for SIPA AP

A New Fron­tier: The In­ner Ear

What happens when a successful biotech venture capitalist is unexpectedly diagnosed with a chronic, life-disrupting vertigo disorder? Innovation in neurotology.

That venture capitalist was Jay Lichter, Ph.D., and after learning there was no FDA-approved drug treatment for his condition, Ménière’s disease, he decided to create a company to bring drug development to neurotology. Otonomy was founded in 2008 and is dedicated to finding new drug treatments for the hugely underserved community living with balance and hearing disorders. Helping patients like Jay has been the driving force behind Otonomy, a company heading into a transformative 2020 with three clinical trial readouts: Phase 3 in Ménière’s disease, Phase 2 in tinnitus, and Phase 1/2 in hearing loss. These catalysts, together with others in the field, highlight the emerging opportunity in neurotology.
Otonomy is leading the way in neurotology
Neurotology, or the treatment of inner ear neurological disorders, is a large and untapped market for drug developers: one in eight individuals in the U.S. have moderate-to-severe hearing loss, tinnitus or vertigo disorders such as Ménière’s disease.1 With no FDA-approved drug treatments available for these conditions, the burden on patients—including social anxiety, lower quality of life, reduced work productivity, and higher rates of depression—can be significant.2, 3, 4

Joe Jimenez, Getty

Ex-No­var­tis CEO Joe Jimenez is tak­ing an­oth­er crack at open­ing a new chap­ter in his ca­reer — and that in­cludes a new board seat and a $250M start­up

Joe Jimenez is back.

The ex-CEO of Novartis has taken a board seat on Century Therapeutics, the Versant and Bayer-backed startup focused on coming up with a brand new twist on cell therapies for cancer — a field where Jimenez made his mark backing the first personalized CAR-T approved for use.

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Can we make the an­tibi­ot­ic mar­ket great again?

The standard for-profit model in drug development is straightforward. Spend millions, even billions, to develop a medicine from scratch. The return on investment (and ideally a tidy profit) comes via volume and/or price, depending on the disease. But the string of big pharma exits and slew of biotech bankruptcies indicate that the model is sorely flawed when it comes to antibiotics.

The industry players contributing to the arsenal of antimicrobials are fast dwindling, and the pipeline for new antibiotics is embarrassingly sparse, the WHO has warned. Drugmakers are enticed by greener pastures, compared to the long, arduous and expensive path to antibiotic approval that offers little financial gain as treatments are typically priced cheaply, and often lose potency over time as microbes grow resistant to them.

Top Har­vard chemist caught up in FBI’s 'T­hou­sand Tal­ents' drag­net, ac­cused of ly­ing about Chi­nese con­nec­tions, pay

The FBI’s probe into the alleged theft of R&D secrets by Chinese authorities has drawn Harvard’s top chemist into its net.

The agency accused Charles M. Lieber, who chairs the university’s chemistry and chemical biology department, with lying about his involvement in China’s Thousand Talents campaign, which was established as a way of drawing in innovators from around the world. And the scientist, 60, was charged with making false statements about his ties to China.

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Eye­ing a trio of tri­al ini­ti­a­tions, Jim Wilson's gene ther­a­py start­up woos Bruce Gold­smith from Deer­field as CEO

Passage Bio — Jim Wilson’s self-described “legacy company” — has wooed a seasoned biotech executive to steer the clinical entry of its first three gene therapy programs.

Bruce Goldsmith jumps to the helm of Passage after a brief CEO stint at Civetta, a cancer-focused startup he helped launch while a venture partner at Deerfield. He takes over from OrbiMed partner and interim chief Stephen Squinto, who will now lead the R&D team.

The FTC and New York state ac­cuse Mar­tin Shkre­li of run­ning a drug mo­nop­oly. They plan to squash it — and per­ma­nent­ly ex­ile him

Pharma bro Martin Shkreli was jailed, publicly pilloried and forced to confront some lawmakers in Washington riled by his move to take an old generic and move the price from $17.50 per pill to $750. But through 4 years of controversy and public revulsion, his company never backed away from the price — left uncontrolled by a laissez faire federal policy on a drug’s cost.

Now the FTC and the state of New York plan to pry his fingers off the drug once and for all and open it up to some cheap competition. And their lawsuit is asking that Shkreli — with several years left on his prison sentence — be banned permanently from the pharma industry.

UP­DAT­ED: Ac­celeron res­ur­rects block­buster hopes for so­tater­cept with pos­i­tive PhII — and shares rock­et up

Acceleron $XLRN says that its first major trial readout of 2020 is a success.

In a Phase II study of 106 patients with pulmonary arterial hypertension (PAH), Acceleron’s experimental drug sotatercept hit its primary endpoint: a significant reduction in pulmonary vascular resistance. The drug also met three different secondary endpoints, including the 6-minute walking test.

“We’re thrilled to report such positive topline results from the PULSAR trial,” Acceleron CEO Habib Dable said in a statement. The company said in a conference call they plan on discussing a Phase III trial design with regulators.

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Short at­tack­er Sahm Ad­ran­gi draws crosshairs over a fa­vorite of Sanofi’s new CEO — with PhII da­ta loom­ing

Sahm Adrang Kerrisdale

Kerrisdale chief Sahm Adrangi took a lengthy break from his series of biotech short attacks after his chief analyst in the field pulled up stakes and went solo. But he’s making a return to drug development this morning, drawing crosshairs over a company that’s one of new Sanofi CEO Paul Hudson’s favorite collaborators.

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Amber Saltzman (Ohana)

Flag­ship's first ven­ture of 2020 is out, and it's all about sperm

A couple years ago, Amber Salzman got a call as she was returning East full-time after a two-year stint running a gene therapy company in California.

It was from someone at Flagship Pioneering, the deep-pocketed biotech venture firm. They had a new company with a new way of thinking about sperm. It had been incubating for over a year, and now they wanted her to run it.

“It exactly fit,” Salzman told Endpoints News. “I just thought I had to do something.”