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

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.


ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology


ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development


CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

UP­DAT­ED: As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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SEC calls out lit­tle Ther­a­peu­tic­sMD for its in­sid­er con­tacts with an­a­lysts to boost share price, then halt rout

Back in May 2017, following an FDA rejection, TherapeuticsMD saw its share price plummet to the lowest levels in two years. The little Florida biotech eventually found its way back to the good side of regulators, scoring a curious OK a year later for its therapy preventing vaginal pain during sex. But the SEC is now accusing it of selectively disclosing nonpublic information in attempts to manipulate its stock.

In two instances in June and July of 2017, TherapeuticsMD allegedly violated the Regulation Fair Disclosure rule by sharing material information with certain sell-side analysts and not the public, resulting in a more favorable stock move than otherwise would be expected.

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Therapists Marcela Ot'alora and Bruce Poulter are trained to conduct MDMA-assisted psychotherapy. In this reenactment, they demonstrate how they help guide and watch over a patient who is revisiting traumatic memories while under the influence of MDMA. (Photo: Multidisciplinary Association for Psychedelic Studies)

MD­MA, now in Phase III, shows promise as a PTSD treat­ment

The first time Lori Tipton tried MDMA, she was skeptical it would make a difference.

“I really was, at the beginning, very nervous,” Tipton said.

MDMA is the main ingredient in the club drug known as ecstasy or molly. But Tipton wasn’t taking pills sold on the street to get high. She was trying to treat her post-traumatic stress disorder by participating in a clinical trial.

After taking a dose of pure MDMA, Tipton lay in a quiet room with two specially trained psychotherapists. They sat next to her as she recalled some of her deepest traumas, such as discovering her mother’s body after Tipton’s mother killed two people and then herself in a murder-suicide.

Ted Ashburn. Oncorus

Cowen, Per­cep­tive lead $79.5M Se­ries B for 's­tand­out' biotech shep­herd­ing on­colyt­ic virus to clin­ic

As several Big Pharma players secure biotech partners in the oncolytic virus space for new immuno-oncology combos, Cowen and Perceptive Advisors have come out with their own bet on a startup that promises to shine.

The marquee investors are joining MPM, Deerfield, Celgene, Astellas, Arkin Bio Ventures and UBS Oncology Impact Fund in backing the drug developer, Oncorus, which will now deploy the $79.5 million in Series B cash toward clinical development of its lead program. Other new investors include Surveyor Capital, Sphera Funds, IMM Investment, QUAD Investment Management, UTC Investment, SV Investment Corp and Shinhan Investment-Private Equity, the last five of which are Korean-based funds.

Fu­til­i­ty analy­sis au­gurs de­feat in piv­otal tri­al test­ing of Nu­Cana's lead drug in metasta­t­ic pan­cre­at­ic can­cer

Nearly two years after making its public debut, UK-based NuCana’s mission to make chemotherapies more potent and safer was dealt a blow, after a pivotal study testing its lead experimental drug halted enrollment in a hard-to-treat advanced form of cancer, following a futility analysis.

The drug, Acelarin, is being evaluated for use in metastatic pancreatic cancer patients who were not considered suitable for combination chemotherapy. In the late-stage ACELARATE study — which compared the experimental drug against the chemotherapy gemcitabine — 200 patients had been enrolled by the sponsor, Clatterbridge Cancer Centre, before an analysis from an independent safety and data monitoring panel suggested the study’s main goal would not be met.