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.

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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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

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Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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George Yancopoulos (Regeneron)

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Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

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Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

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Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Pos­i­tive Covid-19 vac­cine da­ta? New mouse study? OWS in­clu­sion? Yep, but some­how, the usu­al tid­bits from In­ovio back­fire

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Seat­tle Ge­net­ics, Gen­mab turn on TV for a high­light reel in cer­vi­cal can­cer — but a ri­val biotech promis­es a bet­ter show

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