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

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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Mer­ck scraps their $425M Covid-19 drug in lat­est pan­dem­ic set­back

Seven months after paying $425 million cash to acquire it, Merck is scrapping a Covid-19 drug they hoped could provide one of the only treatments for severe hospitalized patients.

Merck’s decision comes after they faced significant and unexpected regulatory delays in getting the drug, known as MK-7110 or CD24Fc, across the finish line. The Big Pharma licensed the drug under the belief that it had already shown sufficient benefit in severe patients and they could help scale it up far faster than OncoImmune, its former owner, could. But in February, the company reported that the FDA insisted Merck run a new trial before seeking authorization.

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Severin Schwan, Roche CEO (Georgios Kefalas/Keystone via AP Images)

Look­ing to ce­ment its lead in packed MS mar­ket, Roche's Ocre­vus un­corks new da­ta in ear­ly-stage pa­tients

Among a positively jam-packed multiple sclerosis market, Roche’s Ocrevus has managed to stand out for what the Swiss drugmaker is calling the most successful launch in its long history. But in order to press its advantage, Ocrevus is looking to earlier-stage patients, and new interim data should help build its case there.

After 48 weeks on Roche’s Ocrevus, 85% of newly diagnosed primary progressing or relapsing MS patients without a history of disease modifying therapy posted no disease activity, including disease progression or relapse, according to interim data set to be presented this weekend at the virtual American Academy of Neurology meeting.

J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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