Sci­en­tists hold out hope for re­gen­er­a­tive in­fu­sion via brain im­plant — de­spite fail­ing its first test in Parkin­son's

A re­gen­er­a­tive ap­proach to treat­ing Parkin­son’s dis­ease — fea­tur­ing an im­plant to pump a pro­tein di­rect­ly in­to pa­tients’ brains — floun­dered on its first clin­i­cal test, but that hasn’t stopped re­searchers in the UK from hold­ing out hope that it can even­tu­al­ly work by restor­ing dam­aged brain cells.

Cham­pi­oned by Parkin­son’s UK, the treat­ment works by boost­ing the lev­els of GDNF, or glial cell line de­rived neu­rotroph­ic fac­tor, a nat­u­ral­ly oc­cur­ring pro­tein thought to pro­tect cells and help them re­cov­er or re­grow. To re­ceive the pro­tein — which is too large to pen­e­trate the blood-brain bar­ri­er — pa­tients first have to un­der­go a ro­bot-as­sist­ed surgery to have four tubes placed in­to their brains, then get hooked to a ma­chine that in­fuse GDNF to pre­cise lo­ca­tions of the brain via a port on the side of the head.

Af­ter con­firm­ing safe­ty with six pa­tients, sci­en­tists re­cruit­ed 35 more pa­tients to see if in­fus­ing GDNF this way led to im­prove­ments in Parkin­son’s symp­toms, from mo­tor move­ments to dai­ly ac­tiv­i­ties.

The short an­swer is no: The “en­cour­ag­ing signs of im­prove­ments” among pa­tients in the drug arm did not con­sti­tute a sig­nif­i­cant dif­fer­ence from the place­bo group.

Alan Whone

But prin­ci­pal in­ves­ti­ga­tor Alan Whone was quick to of­fer po­ten­tial ex­pla­na­tions, name­ly the short dou­ble-blind tri­al time (nine months), the rel­a­tive­ly low dosage of GDNF, and the stage that pa­tients were al­ready at by the time they en­rolled.

His op­ti­mism is backed up by some ev­i­dence that GDNF had promis­ing ef­fects on brain cells al­ready rav­aged by the dis­ease — show­ing a 100% im­prove­ment in a key area of the brain af­fect­ed in the con­di­tion com­pared to place­bo, which didn’t in­duce any change.

“The spa­tial and rel­a­tive mag­ni­tude of the im­prove­ment in the brain scans is be­yond any­thing seen pre­vi­ous­ly in tri­als of sur­gi­cal­ly de­liv­ered growth-fac­tor treat­ments for Parkin­son’s,” Whone said in a state­ment. “This rep­re­sents some of the most com­pelling ev­i­dence yet that we may have a means to pos­si­bly reawak­en and re­store the dopamine brain cells that are grad­u­al­ly de­stroyed in Parkin­son’s.”

Fur­ther­more, a nine-month fol­low-up pe­ri­od dur­ing which the place­bo group al­so switched to GNDF saw all par­tic­i­pants demon­strat­ing “mod­er­ate to large im­prove­ment in symp­toms” com­pared to their own base­line scores, bol­ster­ing the hope that the ef­fects on symp­toms were just lag­ging be­hind im­prove­ment in brain cells.

Erich Mohr

All of this spells “ex­cit­ing signs of promise” for de­vice man­u­fac­tur­er Ren­ishaw as well as Med­Ge­n­e­sis, the biotech de­vel­op­ing GDNF and div­ing in­to an in­creas­ing­ly crowd­ed field with plen­ty of small­er play­ers tied up with big part­ners, tout­ing new tech­nolo­gies like pro­tein degra­da­tion to gene ther­a­py.

“We be­lieve this ex­per­i­men­tal Parkin­son’s Dis­ease Com­pos­ite Re­sponse (PD­CORE) may bet­ter cap­ture the full ef­fects of GDNF and we’re work­ing to get it sci­en­tif­i­cal­ly val­i­dat­ed so that it can be used in fu­ture tri­als,” CEO Erich Mohr said.

GDNF de­vice. Cred­it: Mint­Mo­tion for Pas­sion­ate Pro­duc­tions

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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?

Chris Gibson (Photo By Vaughn Ridley/Sportsfile for Web Summit via Getty Images)

Re­cur­sion founders gin for­tunes as IPO back­ers show­er $436M on one of the biggest boasts in AI -- based on some very small deals

In the AI drug development world, boasting often comes with the territory. Yet few can rival Recursion when it comes to claiming the lead role in what company execs like to call the industrialization of drug development, with promises of continued exponential growth in the number of drugs it has in the pipeline.

On Friday, the Salt Lake City-based biotech translated its unicorn-sized boasts into a killer IPO, pricing more than 24 million shares at the high end of its range and bringing in $436 million — with a large chunk of that promised by some deep-pocket backers.

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Covid-19 vac­cine halt drags on, an FDA ap­point­ment at long last, the great CRO con­sol­i­da­tion, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Conference season is upon us, and while we’d much prefer to be wandering down the hallways and presentation rooms in person, the team is ready to cover the most consequential data coming out of these scientific meetings. Get in touch early if you have news to share.

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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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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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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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