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

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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In­vestors give ail­ing Unum a lease on life and a whole new suite of ex­per­i­men­tal can­cer drugs

Investors, it seems, are willing to give Unum Therapeutics one last shot — or at least one last shot to a company of that name.

The ailing cancer biotech, beset by a series of clinical holds and multiple failed lead programs, announced today that they’ve acquired Kiq LLC and that investors are putting in $104 million to advance Kiq’s pipeline of kinase inhibitors. Unum shareholders will now own only 16.2% of the company and CEO Chuck Wilson indicated that the cell therapies the biotech has worked on since its founding may be on their way out, saying Unum will “explore strategic options” for those products.

Covid-19 roundup: Left out no longer, No­vavax se­cures largest Warp Speed deal yet: $1.6B

It looks like Novavax won’t be left out of Operation Warp Speed after all.

A month after the Gaithersburg, MD biotech saw its shares tumble when it was left off the first reported list of finalists for the White House’s Covid-19 vaccine accelerator, HHS and the Department of Defense have announced a $1.6 billion deal to scale up their Covid-19 candidate. It is the largest deal HHS has announced yet, eclipsing the $1.2 billion deal the administration reached with AstraZeneca in May.

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RA Cap­i­tal dou­bles down on Sid­dhartha Mukher­jee's vi­sion for a new cell en­gi­neer­ing ap­proach, lead­ing Vor's $110M Se­ries B

Vor Biopharma is muscling up.

CEO Robert Ang, who was reluctant to divulge the headcount when discussing his move from Neon Therapeutics to Vor last August, readily offered that the team has grown from 6 to 50 in less than a year. The biotech is moving to a larger office on Cambridge Parkway Drive in weeks, giving it more space to complete the IND-enabling work and manufacturing scale-up — conducted by a CDMO partner — in preparation for clinical trials planned for the first half of 2021.

Cel­lec­tis slammed af­ter pa­tient dies and FDA slaps a hold on their tri­al for an off-the-shelf CAR-T for mul­ti­ple myelo­ma

Cellectis was slammed after the market close on Monday as the biotech reported that the FDA demanded it hit the brakes on their MELANI-01 trial for their off-the-shelf cell therapy UCARTCS1A after one of the patients in the study died of treatment-related cardiac arrest.

The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Sec­ond PhI­II study for Idor­si­a's sleep drug re­turns pos­i­tive re­sults, but al­so rais­es new ques­tions

Following a successful Phase III study in April showcasing the safety and potential of its new sleep drug, Idorsia posted some mixed news in the second Phase III study, but that won’t stop a planned filing aimed at regulatory approval.

The drug, a dual orexin receptor antagonist (DORA) called daridorexant, was found to significantly improve sleep maintenance and subjective total sleep time in 25 mg doses, replicating results from the first Phase III study. However, improvements in sleep onset and daytime functioning narrowly missed statistical significance, despite numerical consistency with the April study.

UP­DAT­ED: Im­munomedics spells out PFS ben­e­fit of Trodelvy in mTNBC, hunt­ing a full OK just weeks af­ter ac­cel­er­at­ed ap­proval

By the time the FDA finally granted an accelerated OK for Immunomedics’ Trodelvy, we already got a very strong hint that their confirmatory Phase III study in metastatic triple-negative breast cancer was a success.

That’s because the independent data safety monitoring committee recommended that the trial be stopped early. But just what pointed them to the conclusion was still unclear.

“We do not know the totality of their decision other than it’s pretty evident that the primary endpoint was met; otherwise they could not request to halt the study,” Behzad Aghazadeh, the executive chairman, told Endpoints News at the time.

Shoshanna Shendelman, Applied Therapeutics CEO (Applied Therapeutics)

A lit­tle biotech slaps back at a 'crim­i­nal' short at­tack, vow­ing to pur­sue a pros­e­cu­tion of their case

As short attacks go, Biotech Research Partners’ assault on Applied Therapeutics’ “cherry picked” data and a variety of so-called red flags didn’t cause a whole lot of damage. Ahead of the July 4 holiday, its shares $APLT were dinged and showed signs of quick recovery.

But that didn’t stop an incendiary response, as the biotech swung into action bright and early Monday morning.

Applied Therapeutics accused the authors of the short report of manipulating graphs and figures, misrepresenting data and included factual misrepresentations — all of which added up, in their view, to fraud.

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