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.

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

Genen­tech sub­mits a big plan to ex­pand its South San Fran­cis­co foot­print

The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

Here comes the oral GLP-1 drug for di­a­betes — but No­vo Nordisk is­n't dis­clos­ing Ry­bel­sus price just yet

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

When the hysteria of Zika transmission sprang into the American zeitgeist a few years ago, UK-based Oxitec was already field-testing its male Aedes aegypti mosquito, crafted to possess a gene engineered to obliterate its progeny long before maturation.

But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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[via AP Images]

Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

Jason Kelly. Mike Blake/Reuters via Adobe

Eye­ing big ther­a­peu­tic push, Gink­go bags $290M to build a cell pro­gram­ming em­pire

Ginkgo Bioworks is on a roll. Days after publicizing a plan to nurture new startups via partnerships with accelerators Y Combinator and Petri, the Boston biotech says it has raised another $290 million for its cell programming platform to reach further and wider.

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

The need to limit drug prices is a rare point of agreement between President Trump and Democrats, although the president has yet to comment on the proposal and will likely face pressure to back a more conservative option or no bill at all. Republican Senator Chuck Grassley is reportedly lobbying his fellow party members on a more modest proposal he negotiated with Democratic Senator Ron Wyden in July.

David Grainger [file photo]

'Dis­con­nect the bas­tard­s' — one biotech's plan to break can­cer cell­s' uni­fied de­fens­es

Chemotherapy and radiotherapy are the current gladiators of cancer treatment, but they come with well-known limitations and side-effects. The emergence of immunotherapy — a ferocious new titan in oncologist’s toolbox — takes the brakes off the immune system to kill cancer cells with remarkable success in some cases, but the approach is not always effective. What makes certain forms of cancer so resilient? Scientists may have finally pieced together a tantalizing piece of the puzzle, and a new biotech is banking on a new approach to fill the gap.

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