Ro­bot­ic pill tech found to be safe, tol­er­a­ble in ear­ly hu­man study, paving ground for oral bi­o­log­ics

Trans­form­ing in­jecta­bles in­to pills is hard­ly a nov­el idea, but a string of phar­ma­ceu­ti­cal/chem­i­cal ef­forts to evade the en­zymes that break down the oral drug be­fore it can be ab­sorbed have large­ly hit a wall. Ear­li­er this month, an an­i­mal study cap­tured the spot­light for the po­ten­tial of its blue­ber­ry sized ro­bot­ic pill de­signed to de­liv­er an in­sulin shot in­side the stom­ach — but Cal­i­for­nia-based Rani Ther­a­peu­tics on Thurs­day said it has suc­cess­ful­ly test­ed its ro­bot­ic pill for safe­ty and tol­er­a­bil­i­ty in hu­mans, paving the way for ef­fi­ca­cy stud­ies that could open the door to a colos­sal mar­ket to en­hance treat­ment com­pli­ance, di­min­ish the need for physi­cian-led ther­a­peu­tic ad­min­is­tra­tion and pla­cate nee­dle-pho­bic pa­tients.

Mir Im­ran

The com­pa­ny’s prod­uct — called the Ra­niP­ill — has un­der­gone over 100 pre­clin­i­cal stud­ies, in­clud­ing large an­i­mal tri­als. The cap­sule has an en­teric coat­ing that pro­tects it from the acidic am­bi­ence of the stom­ach, and once it moves in­to the in­tes­tine and pH lev­els rise, the coat­ing dis­solves and a chem­i­cal re­ac­tion takes place which in­flates a bal­loon. Pres­sure in the bal­loon push­es a dis­solv­able mi­cronee­dle filled with the drug in­to the in­testi­nal wall.

In­testines don’t have pain re­cep­tors, and the in­testi­nal sub­strate — which is de­signed to ab­sorb nu­tri­ents — is high­ly vas­cu­lar­ized, mak­ing it the ide­al lo­ca­tion for the drug-en­gorged in­jec­tion to de­ploy, Rani chief Mir Im­ran told End­points News, adding that in the hand­ful of drugs the com­pa­ny test­ed as part of the Ra­niP­ill in an­i­mal stud­ies, the ab­sorp­tion of the drug was gen­er­al­ly equal or high­er than that of a sub­cu­ta­neous in­jec­tion.

Fol­low­ing suc­cess­ful an­i­mal stud­ies, Rani ini­ti­at­ed a study in healthy hu­mans last year to eval­u­ate the fea­si­bil­i­ty of the prod­uct. Two groups of 10 sub­jects each (with one arm hav­ing fed, and the oth­er arm hav­ing fast­ed) were giv­en a drug-free ver­sion of the Ra­niP­ill. Re­sults re­vealed nei­ther group felt the im­pact of the cap­sule in­flat­ing or de­ploy­ing, and each pa­tient suc­cess­ful­ly ex­punged the rem­nants. The cap­sule was well tol­er­at­ed and the pres­ence (or ab­sence) of food in the stom­ach had no im­pact on the per­for­mance of the cap­sule, the com­pa­ny said.

“This is the first time a ro­bot­ic pill was swal­lowed by hu­mans — this re­al­ly paves the way for the next study which will have a drug, and we will be able to mea­sure drug lev­els,” Im­ran said.

The com­pa­ny has cho­sen to use a pill loaded with oc­treotide, an off-patent bi­o­log­ic that treats the hor­mon­al dis­or­der acromegaly, for the up­com­ing study, which the com­pa­ny ex­pects will com­mence in the com­ing months.

“If we’re suc­cess­ful in our next study, it re­al­ly means that we can de­liv­er any drug…in­clud­ing in­sulin and Hu­mi­ra and treat­ments for a whole host of oth­er dis­eases such as mul­ti­ple scle­ro­sis, he­mo­phil­ia and oth­er chron­ic con­di­tions,” he added.

But there’s a long road ahead. Each drug loaded in­to the cap­sule will re­quire a sep­a­rate study be­fore Rani can pe­ti­tion the FDA for ap­proval.

Mean­while, rat and pig da­ta on the oth­er ro­bot­ic pill — cre­at­ed by a team of re­searchers at MIT (in­clud­ing the pro­lif­ic drug de­liv­ery mae­stro Robert Langer) and No­vo Nordisk $NVO — an­nounced ear­li­er in Feb­ru­ary, has an al­ter­na­tive mech­a­nism of ac­tion.

The de­vice, called So­ma, en­cap­su­lates a nee­dle in­side a pill made of com­pressed freeze-dried in­sulin that is de­signed to ori­ent it­self when it comes in con­tact with the stom­ach lin­ing — in­spired by a leop­ard tor­toise, which bran­dish­es a shell that al­lows the African rep­tile to right it­self if it rolls on­to its back. Up­on con­tact with the wet in­ner lin­ing of the stom­ach (which is al­so de­void of pain re­cep­tors), a sug­ar disk hold­ing the nee­dle in place is dis­solved, mak­ing way for the nee­dle to re­lease its con­tents. The prod­uct is then en­gi­neered to dis­in­te­grate and trav­el harm­less­ly through the di­ges­tive sys­tem and even­tu­al­ly be elim­i­nat­ed, the re­searchers wrote in their re­port in Sci­ence. 

“One big dif­fer­ence is that we pre­date the MIT ef­fort by at least 5 years and our IP re­al­ly cov­ers every­thing they’re do­ing…their (So­ma’s) spring loaded de­liv­ery is some­thing we have very strong patents on, so I think they are go­ing to step on our IP. The de­sign of the nee­dle we have very strong patents on, and their nee­dle looks ex­act­ly like our nee­dle,” Im­ran said, em­pha­siz­ing the size of Rani’s patent port­fo­lio, which he claimed in­cludes 70 is­sued patents.

“The MIT group as far as we can tell has two patent ap­pli­ca­tions and nei­ther has been is­sued. Cer­tain­ly for us we see that (com­pe­ti­tion) as a pos­i­tive be­cause it val­i­dates our ap­proach in a very fun­da­men­tal way — not that we need that val­i­da­tion thanks to our an­i­mal stud­ies — but it’s re­al­ly nice to have Bob Langer on my heels.”

In re­sponse to Im­ran’s com­men­tary, Langer sug­gest­ed it was un­clear whether the MIT ap­proach is in­fring­ing on Rani’s patents.

Bob Langer

“I think it’s un­clear at this time — rec­og­niz­ing that we, Rani, and I’m sure oth­ers have a num­ber of patent ap­pli­ca­tions in this area — whether, for some ap­pli­ca­tions we are step­ping on their patents, they are step­ping on ours, and/or there are patents by oth­ers which will be im­por­tant,” he said in an emailed state­ment.

“Our goal in pub­lish­ing our work in a top peer re­viewed sci­en­tif­ic jour­nal (Sci­ence) was to get the sci­en­tif­ic prin­ci­ples we de­vel­oped out to the sci­en­tif­ic com­mu­ni­ty in the hopes that it can get to pa­tients. If that hap­pens through us, our col­lab­o­ra­tors at No­vo Nordisk, Rani, or some­one else, we will have achieved our goal.”

Found­ed in 2012, Rani Ther­a­peu­tics has raised $142 mil­lion in fund­ing from a slate of in­vestors in­clud­ing GV (the in­vest­ment arm of Al­pha­bet), and counts No­var­tis and Shire as its part­ners.

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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