Mid-stage da­ta on Al­lena's hy­per­ox­aluria drug fu­el op­ti­mism ahead of piv­otal read­out

Ahead of the piv­otal da­ta of its lead ex­per­i­men­tal drug for hy­per­ox­aluria, Al­lena Phar­ma­ceu­ti­cals re­vealed in­ter­im da­ta from a small mid-stage study on Wednes­day, that sig­naled the drug con­fers ben­e­fits in cer­tain pa­tients with ad­vanced chron­ic kid­ney dis­ease (CKD) that are at risk of sys­temic ox­alo­sis, a po­ten­tial­ly life-threat­en­ing con­di­tion.

Hy­per­ox­aluria oc­curs due to high lev­els of ox­alate — a nat­ur­al chem­i­cal — in urine. Ox­alo­sis oc­curs af­ter the kid­neys fail in in­di­vid­u­als who have pri­ma­ry and in­testi­nal caus­es of hy­per­ox­aluria, and ex­cess ox­alate builds up in the blood. This can lead to ox­alate de­posits in blood ves­sels, bones and body or­gans, ac­cord­ing to the Mayo Clin­ic.

The com­pa­ny dis­closed da­ta from study 206 in­volv­ing sev­en pa­tients with pro­gres­sion of pri­ma­ry hy­per­ox­aluria (PH) — a rare con­di­tion char­ac­ter­ized by re­cur­rent kid­ney and blad­der stones — or en­teric hy­per­ox­aluria (EH), which pre­dis­pos­es pa­tients to ex­cess ox­alate ab­sorp­tion due to an un­der­ly­ing gas­troin­testi­nal dis­or­der.

In the sin­gle-arm tri­al, de­signed to en­roll be­tween 15 and 20 pa­tients, who were oral­ly ad­min­is­tered 7,500 units of relox­aliase for 12 con­sec­u­tive weeks. The pri­ma­ry end­points of the tri­al are chang­ing from base­line in 24-hour urine ox­alate (UOx) and plas­ma ox­alate (POx) se­cre­tions (UOx was col­lect­ed for pa­tients who are not on dial­y­sis).

All four EH pa­tients ex­pe­ri­enced an av­er­age re­duc­tion of 40% in POx com­pared to base­line. The two pa­tients not on dial­y­sis al­so ex­pe­ri­enced re­duc­tions in UOx of 29% and 42%, re­spec­tive­ly. Three pa­tients with PH type 2 or PH type 3 with pre­served re­nal func­tion were treat­ed — one pa­tient had a >20% mean re­duc­tion in UOx ex­cre­tion, while the oth­er two pa­tients did not show a re­sponse to relox­aliase, Al­lena $AL­NA said on Tues­day.

“Over­all, we see the da­ta as en­cour­ag­ing for the EH pop­u­la­tion (in­clud­ing those with chron­ic kid­ney dis­ease), but murki­er for the PH pop­u­la­tion,” Cred­it Su­isse an­a­lysts said. “While this is a small set­back, we see Al­lena’s plan to nar­row its fur­ther eval­u­a­tion of relox­aliase in PH to pa­tients with com­pro­mised re­nal func­tion and where the drug’s GI mech­a­nism of ac­tion may play a more im­por­tant role as sen­si­ble. We al­so note that PH is a much small­er mar­ket op­por­tu­ni­ty in gen­er­al, giv­en that there are on­ly ~5,000 pa­tients in the US (vs. ~250,000 in the US with EH).”

The da­ta pro­vides op­ti­mism ahead of the Phase III read­out, an­a­lysts said. Topline da­ta from the late-stage study is ex­pect­ed in the sec­ond half of the year — and an ad­di­tion­al study 206 da­ta is al­so in­com­ing.

“Im­por­tant­ly, two stage 3 pts met Ph3 in­clu­sion cri­te­ria, pro­vid­ing +ve read-through to on­go­ing Ph3’s giv­en sim­i­lar end­point, study length, dose strength and dos­ing fre­quen­cy. Mean 35% re­duc­tion in UOx ex­ceed­ed the tar­get 20% in Ph3’s,” Jef­feries an­a­lysts wrote.

Ahead of the late-stage read­out, Baird an­a­lysts had al­so un­der­scored the im­por­tance of a clean safe­ty pro­file af­ter dos­ing fre­quen­cy was changed from 3 times dai­ly to 5 times dai­ly.  “While the cur­rent re­sults on­ly in­clude 4 pa­tients with EH, the ab­sence of treat­ment-re­lat­ed se­ri­ous ad­verse events for relox in the bas­ket tri­al gives us fur­ther con­fi­dence for the en­zyme’s safe­ty pro­file in URIROX-1/2, par­tic­u­lar­ly as these 4 EH pa­tients were sub­stan­tial­ly se­vere cas­es…In short, to­day’s bas­ket da­ta, while ear­ly, give us in­cre­men­tal op­ti­mism for relox’s tol­er­a­bil­i­ty in piv­otal stud­ies in EH.”

Relox­aliase is a crys­talline for­mu­la­tion of the en­zyme ox­alate de­car­boxy­lase, which de­grades ox­alate with­in the gas­troin­testi­nal tract, there­by lim­it­ing sys­temic ab­sorp­tion of ox­alate in­to the blood­stream. This re­duces the bur­den on the kid­ney to fil­ter and ex­crete ox­alate in the urine and, in turn, di­min­ish­es the risk of kid­ney stones and oth­er se­ri­ous re­nal dis­or­ders.


Im­age: Shut­ter­stock

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.”