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

UP­DAT­ED: In sur­prise switch, Bris­tol-My­ers is sell­ing off block­buster Ote­zla, promis­ing to com­plete Cel­gene ac­qui­si­tion — just lat­er

Apart from revealing its checkpoint inhibitor Opdivo blew a big liver cancer study on Monday, Bristol-Myers Squibb said its plans to swallow Celgene will require the sale of blockbuster psoriasis treatment Otezla to keep the Federal Trade Commission (FTC) at bay.

The announcement — which has potentially delayed the completion of the takeover to early 2020 — irked investors, triggering the New York-based drugmaker’s shares to tumble Monday morning in premarket trading.

Celgene’s Otezla, approved in 2014 for psoriasis and psoriatic arthritis, is a rising star. It generated global sales of $1.6 billion last year, up from the nearly $1.3 billion in 2017. Apart from the partial overlap of Bristol-Myers injectable Orencia, the company’s rival oral TYK2 psoriasis drug is in late-stage development, after the firm posted encouraging mid-stage data on the drug, BMS-986165, last fall. With Monday’s decision, it appears Bristol-Myers is favoring its experimental drug, and discounting Otezla’s future.

The move blindsided some analysts. Credit Suisse’s Vamil Divan noted just days ago:

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Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Fol­low­ing news of job cuts in Eu­ro­pean R&D ops, Sanofi con­firms it’s of­fer­ing US work­ers an 'ear­ly ex­it'

Ear­li­er in the week we learned that Sanofi was bring­ing out the bud­get ax to trim 466 R&D jobs in Eu­rope, re­tool­ing its ap­proach to car­dio as re­search chief John Reed beefed up their work in can­cer and gene ther­a­pies. And we’re end­ing the week with news that the phar­ma gi­ant has al­so been qui­et­ly re­duc­ing staff in the US, tar­get­ing hun­dreds of jobs as the com­pa­ny push­es vol­un­tary buy­outs with a fo­cus on R&D sup­port ser­vices.

Suf­fer­ing No­var­tis part­ner Cona­tus is pack­ing it in on NASH af­ter a se­ries of un­for­tu­nate tri­al events

The NASH par­ty is over at No­var­tis-backed Cona­tus. And this time they’re turn­ing off the lights.

More than 2 years af­ter No­var­tis sur­prised the biotech in­vest­ment com­mu­ni­ty with its $50 mil­lion up­front and promise of R&D sup­port to part­ner with the lit­tle biotech on NASH — ig­nit­ing a light­ning strike for the share price — Cona­tus $CNAT is back with the lat­est bit­ter tale to tell about em­ri­c­as­an, which once in­spired con­fi­dence at the phar­ma gi­ant.

Bet­ter than Am­bi­en? Min­er­va soars on PhI­Ib up­date on sel­torex­ant for in­som­nia

A month af­ter roil­ing in­vestors with what skep­tics dis­missed as cher­ry pick­ing of its de­pres­sion da­ta, Min­er­va is back with a clean slate of da­ta from its Phase IIb in­som­nia tri­al.

In a de­tailed up­date, the Waltham, MA-based biotech said sel­torex­ant (MIN-202) hit both the pri­ma­ry and sev­er­al sec­ondary end­points, ef­fec­tive­ly im­prov­ing sleep in­duc­tion and pro­long­ing sleep du­ra­tion. In­ves­ti­ga­tors made a point to note that the ef­fects were con­sis­tent across the adult and el­der­ly pop­u­la­tions, with the lat­ter more prone to the sleep dis­or­der.

Gene ther­a­py biotech sees its stock rock­et high­er on promis­ing re­sults for rare cas­es of but­ter­fly dis­ease

Shares of Krys­tal Biotech took off this morn­ing $KRYS af­ter the lit­tle biotech re­port­ed promis­ing re­sults from its gene ther­a­py to treat a rare skin dis­ease called epi­der­mol­y­sis bul­losa.

Fo­cus­ing on an up­date with 4 new pa­tients, re­searchers spot­light­ed the suc­cess of KB103 in clos­ing some stub­born wounds. Krys­tal says that of 4 re­cur­ring and 2 chron­ic skin wounds treat­ed with the gene ther­a­py, the KB103 group saw the clo­sure of 5. The 6th — a chron­ic wound, de­fined as a wound that had re­mained open for more than 12 weeks — was par­tial­ly closed. That brings the to­tal so far to 8 treat­ed wounds, with 7 clo­sures.

Ab­b­Vie gets a green light to re­sume re­cruit­ing pa­tients for one myelo­ma study — but Ven­clex­ta re­mains un­der a cloud

Three months af­ter reg­u­la­tors at the FDA forced Ab­b­Vie to halt en­rolling pa­tients in its tri­als of a com­bi­na­tion us­ing Ven­clex­ta (vene­to­clax) to treat drug-re­sis­tant cas­es of mul­ti­ple myelo­ma, the agency has green-light­ed the re­sump­tion of one of those stud­ies, while keep­ing the rest on the side­lines.

The CANO­VA (M13-494) study can now get back in busi­ness re­cruit­ing pa­tients to test the drug for a pop­u­la­tion that shares a par­tic­u­lar ge­net­ic bio­mark­er. To get that per­mis­sion, Ab­b­Vie — which is part­nered with Roche on this pro­gram — was forced to re­vise the pro­to­col, mak­ing un­spec­i­fied changes in­volv­ing risk mit­i­ga­tion mea­sures, pro­to­col-spec­i­fied guide­lines and an up­dat­ed fu­til­i­ty cri­te­ria.

Bris­tol-My­ers star Op­di­vo fails sur­vival test in a matchup with Nex­avar aimed at shak­ing up the big HCC mar­ket

Bris­tol-My­ers Squibb has suf­fered an­oth­er painful set­back in its years-long quest to ex­pand the reach of Op­di­vo. The phar­ma gi­ant this morn­ing not­ed that their Check­mate-459 study com­par­ing Op­di­vo with Bay­er’s Nex­avar in front­line cas­es of he­pa­to­cel­lu­lar car­ci­no­ma — the most com­mon form of liv­er can­cer — failed to hit the pri­ma­ry end­point on over­all sur­vival.

This was a sig­nif­i­cant mile­stone in Bris­tol-My­ers’ tal­ly of PD-1 cat­a­lysts this year. Nex­avar (so­rafenib) has been the stan­dard of care in front­line HCC for the past decade, though Op­di­vo has been mak­ing head­way in sec­ond-line HCC cas­es, where it’s go­ing toe-to-toe with Bay­er’s Sti­var­ga (re­go­rafenib) af­ter re­cent ap­provals shook up the mar­ket.

Dean Hum. Nasdaq via YouTube

Gen­fit goes to Chi­na with a deal worth up to $228M for NASH drug

Fresh off the high of its Nas­daq IPO de­but, and the low of com­par­isons to Cymabay — whose NASH drug re­cent­ly stum­bled — Gen­fit on Mon­day un­veiled an up to $228 mil­lion deal with transpa­cif­ic biotech Terns Phar­ma­ceu­ti­cals to de­vel­op its flag­ship ex­per­i­men­tal liv­er drug — elafi­bra­nor — in Greater Chi­na.

The deal comes weeks af­ter Gen­fit $GN­FT is­sued a fiery de­fense of its dual PPAR ag­o­nist elafi­bra­nor, when com­peti­tor Cymabay’s PPARδ ag­o­nist, se­ladel­par, fiz­zled in a snap­shot of da­ta from an on­go­ing mid-stage tri­al. The main goal at the end of 12 weeks was for se­ladel­par to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in liv­er fat con­tent, but da­ta showed that pa­tients on the place­bo ac­tu­al­ly per­formed bet­ter.