As head-to-head with Alex­ion heats up, No­var­tis flash­es da­ta for next wave of tri­als for star kid­ney mol­e­cule

No­var­tis has rarely in­vest­ed much in kid­ney drugs, but over the last cou­ple of years, they’ve tried to build a pipeline out of a sin­gle drug.

On Sun­day, that drug, a small mol­e­cule called ip­ta­co­pan, de­liv­ered an­oth­er suc­cess. No­var­tis an­nounced that it cleared a Phase II tri­al for the rare kid­ney dis­ease IgA nephropa­thy, sig­nif­i­cant­ly re­duc­ing a risk fac­tor for kid­ney health. The da­ta bur­nish the Swiss phar­ma’s con­fi­dence in a piv­otal Phase III study al­ready un­der­way in the con­di­tion, along with the mid- or late-stage stud­ies they’ve launched in a hand­ful of un­com­mon re­nal af­flic­tions.

Col­lec­tive­ly, they add a sec­ondary set of mar­kets for the drug, even if it proves un­suc­cess­ful in un­seat­ing Alex­ion in PNH, where the drug re­cent­ly won an FDA break­through des­ig­na­tion.

John Tsai

“Com­ple­ment-dri­ven re­nal dis­eases, such as IgAN, are dev­as­tat­ing and most­ly af­fect young adults, im­pos­ing a high dis­ease bur­den,” No­var­tis CMO John Tsai said in a state­ment. “These new da­ta in IgAN add to the grow­ing body of ev­i­dence around the po­ten­tial of ip­ta­co­pan to tar­get a key dri­ver in these rare re­nal dis­eases.”

In the 112-per­son study, IgA nephropa­thy pa­tients were ran­dom­ized to re­ceive place­bo or var­i­ous dos­es of ip­ta­co­pan. Pa­tients who re­ceived the high­est dose — the one they brought for­ward in­to Phase III — saw a 23% re­duc­tion in pro­tein­uria, or the amount of pro­tein, pa­tients re­leased in urine. A cor­re­late for how well the kid­neys are fil­ter­ing, the FDA has re­cent­ly ac­cept­ed it as a sur­ro­gate end­point for ac­cel­er­at­ed ap­proval.

No­var­tis said the drug al­so showed a “trend to­ward sta­bi­liza­tion” in glomeru­lar fil­tra­tion rate, a more es­tab­lished mea­sure for kid­ney func­tion, but de­clined to dis­close the ac­tu­al da­ta in their press re­lease. The two mea­sures are co-pri­ma­ry end­points on the Phase III stud­ies.

IgA nephropa­thy has no ap­proved treat­ments, but as the FDA has up­dat­ed its re­quire­ments for ap­prov­ing new kid­ney drugs and phar­ma and VC cash has poured in­to the space, the hunt for one has grown hot­ly com­pet­i­tive. Swedish biotech Cal­lid­i­tas snared a $90 mil­lion IPO last year most­ly on the promise of its Phase III steroid for the dis­ease. In Jan­u­ary, GV-backed Tru­code Gene Re­pair re­vealed they de­cid­ed to abrupt­ly scrap their en­tire gene edit­ing plat­form and sick­le cell dis­ease fo­cus on the hope that they could turn an old Mer­ck KGaA drug in­to the first treat­ment for the dis­ease. (They re­brand­ed as Ve­ra and went for a mod­est IPO.)

Like the oth­er dis­eases No­var­tis is fir­ing ip­ta­co­pan at, IgA nephropa­thy is dri­ven by a dys­func­tion­al im­mune sys­tem, in par­tic­u­lar prob­lems with a cas­cade called the com­ple­ment sys­tem. The most ad­vanced pro­gram is for PNH, the most well-known com­ple­ment dis­or­der, but one where No­var­tis faces stiff com­pe­ti­tion in es­tab­lished gi­ant Alex­ion and a new­com­er in Apel­lis, whose drug Em­paveli won ap­proval last month.

The com­pa­ny will have a clear­er path to com­mer­cial dom­i­nance in kid­ney dis­eases, where few, if any, oth­er op­tions are avail­able. On Mon­day, the com­pa­ny an­nounced up­dat­ed da­ta from their Phase II tri­al for CG nephropa­thy, al­so known as C3G, show­ing im­proved kid­ney func­tion from pa­tients on the drug. A Phase III tri­al will start lat­er this year.

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

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Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

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Hal Barron, GSK R&D chief (Endpoints News)

Hal Bar­ron gam­bles $625M cash on high-wire TIG­IT act, throw­ing Glax­o­SmithK­line in­to heat­ed race and com­plet­ing next-gen I/O trin­i­ty

Count Hal Barron and GlaxoSmithKline in for the TIGIT fight.

The stakes are as high as the risks: While a growing pack of Big Pharma rivals is lending credence to the hypothesis that TIGIT will be the next big immune checkpoint and cancer drug target, the first clinical trials have shown response rates that can be described as modest at best. But Barron’s bet is on the whole “axis” that the receptor sits on, with an eye on testing its new anti-TIGIT antibody not just in combo with PD-1 but also in triplets.

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Michel Sade­lain puts his name and new cell en­gi­neer­ing tech be­hind 'ag­nos­tic' CAR-T start­up chas­ing epi­ge­net­ic anti­gens

It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

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Geoffrey Porges, SVB Leerink

Top an­a­lyst maps a rocky road for Ver­tex — un­less they adopt a $10B M&A cam­paign to save the pipeline

After repeatedly poking Vertex $VRTX execs with pointed criticism of their R&D strategy, top SVB Leerink analyst Geoffrey Porges is now turning up the heat to a full-scale roasting.

In a note out early Monday morning, Porges spotlights the impact of Vertex’s recent follow-up failure on AATD — their treatment hit the endpoint but missed on commercial prospects — rewriting his recommended scenario for CEO Reshma Kewalramani as she grapples with the setback.

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Lynn Fitch, Mississippi Attorney General (Rogelio V. Solis/AP Images)

Mis­sis­sip­pi sues Eli Lil­ly, Sanofi and No­vo over in­sulin prices as in­ter­change­able biosim­i­lars may ar­rive soon

Mississippi Attorney General Lynn Fitch last week sued the top three insulin manufacturers, which collectively cover almost the entire US insulin market, alleging that they’ve colluded to raise their prices in lockstep, and in some cases by more than 1,000% for drugs that are decades old.

“Because of Manufacturer Defendants’ collusive price increases, nearly a century after the discovery of insulin, diabetes medications have become unaffordable for many diabetics,” the lawsuit says.

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Andrew Hopkins, Exscientia CEO

Ex­sci­en­tia spends Soft­Bank's cash in bid to edge out AI ri­vals

Exscientia is sprinting to win the great AI biotech race.

The UK company, having long labored on small discovery deals with large pharmas, raised up to $525 million in a Series D led by the infamous Japanese conglomerate SoftBank in April and followed it up less than a month later with a Bristol Myers Squibb deal that paid $50 million cash and $1.2 billion in milestones.

Now, the Oxford spinout is splurging on a shiny new tool. On Monday they announced they purchased the three-year-old molecule-screening biotech Allcyte, a longtime collaborator, for $60.6 million in cash and stock.

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As­traZeneca's Covid-19 an­ti­body cock­tail miss­es the mark in pre­vent­ing symp­toms post-ex­po­sure

As the field for monoclonal antibody treatments of Covid-19 grows more crowded, AstraZeneca has announced a study of its own cocktail AZD7442 did not meet its main goal of preventing symptomatic Covid-19.

The company’s long-acting antibody combo was used in a trial with unvaccinated adults about the age of 18 with confirmed exposure. AZD7442 reduced the risk by just 33%, a figure that was not statistically significant.