Reata's bar­dox­olone of­fers promise in pa­tients with rare kid­ney dis­or­der

Af­ter sur­pris­ing Wall Street with pos­i­tive da­ta on its drug, omavelox­olone, in pa­tients suf­fer­ing from a no­to­ri­ous­ly hard-to-treat de­gen­er­a­tive neu­ro­mus­cu­lar dis­or­der last month, Rea­ta Phar­ma on Mon­day un­veiled piv­otal re­sults from a tri­al test­ing an­oth­er drug, bar­dox­olone, in pa­tients with a rare, ge­net­ic form of chron­ic kid­ney dis­ease for which there ex­ist no ap­proved ther­a­pies.

Bar­dox­olone, like Rea­ta’s oth­er lead drug — omavelox­olone — is a small mol­e­cule en­gi­neered to bind to a gene called Keap1 to en­hance the ac­tiv­i­ty of the pro­tein Nrf2 in or­der to defuse in­flam­ma­tion.

The Phase III por­tion of the CAR­DI­NAL study en­rolled 157 pa­tients with Al­port syn­drome — which is char­ac­ter­ized by pro­gres­sive loss in the kid­ney’s ca­pac­i­ty to fil­ter blood — were ei­ther giv­en bar­dox­olone or place­bo. The main goal of this tranche of the study was a change in eGFR (es­ti­mat­ed Glomeru­lar Fil­tra­tion Rate), a key mea­sure of the kid­ney’s abil­i­ty to pu­ri­fy blood, af­ter 48 weeks of treat­ment. The main sec­ondary end­point was the change in the re­tained eGFR af­ter 48 weeks of treat­ment and four weeks of drug with­draw­al.

Bri­an Sko­r­ney

Da­ta showed pa­tients treat­ed with bar­dox­olone had a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment com­pared to place­bo in mean eGFR of 9.50 mL/min (p<0.0001) at 48 weeks — (in the bar­dox­olone arm pa­tients saw an in­crease of 4.72 mL/min  from base­line, while place­bo-treat­ed pa­tients saw of de­cline of -4.78 mL/min).

Mean­while, at week 52 fol­low­ing a month with­draw­al af­ter 48 weeks of treat­ment — bar­dox­olone in­duced a sta­tis­ti­cal­ly sig­nif­i­cant place­bo-cor­rect­ed ben­e­fit in mean re­tained eGFR of 5.14 mL/min (p=0.0012). In the bar­dox­olone arm, pa­tients ex­pe­ri­enced a mean re­tained eGFR de­cline of 0.96 mL/min, while pa­tients treat­ed with place­bo saw their rate slump by 6.11 mL/min.

“While the mag­ni­tude of re­tained ben­e­fit at 52 weeks in this Phase 3 study may not have been as great as the 8.3mL/min place­bo-cor­rect­ed ben­e­fit they had pro­ject­ed, and the ac­tive arm saw less of a re­tained ben­e­fit than in pre­vi­ous stud­ies, we still view this re­sult as sig­nif­i­cant,” Baird’s Bri­an Sko­r­ney wrote in a note, not­ing that the trou­ble seems to be if ear­ly eGFR im­prove­ments match those pre­vi­ous­ly seen on treat­ment of around 10mL/min, a de­cline from +10mL/min to +5mL/min could be­come a con­cern.

Joseph Schwartz SVB Leerink

SVB Leerink an­a­lyst Joseph Schwartz echoed the same con­cern. “Up­on clos­er scruti­ny, we think bears may in­ter­pret the ab­solute re­tained ben­e­fit da­ta as dis­ap­point­ing (i.e., bar­dox­olone (Bard) arm falling be­low base­line) will look for more de­tailed pro­tein­uria da­ta in or­der to dis­prove the po­ten­tial for hy­per­fil­tra­tion,” he said. Al­port syn­drome pa­tients typ­i­cal­ly have el­e­vat­ed pro­tein lev­els in their urine, or pro­tein­uria.

Shares of the Texas-based drug de­vel­op­er $RE­TA slipped about 4.4% to $204.25 in Tues­day pre­mar­ket trad­ing.

But both an­a­lysts were large­ly con­vinced by the ev­i­dence sup­port­ive of the drug’s use in this pa­tient pop­u­la­tion.

“Nev­er­the­less, in light of the high ef­fi­ca­cy bar that RE­TA had set in Ph.3 CAR­DI­NAL as well as the high un­met need in a mo­ti­vat­ed pt. pop­u­la­tion, we con­tin­ue to think that bar­dox­olone of­fers a valu­able ther­a­peu­tic ben­e­fit for pts. in pre­serv­ing kid­ney func­tion,” Schwartz said.

Rea­ta, which is test­ing bar­dox­olone in a range of rare kid­ney dis­eases, should be able to repli­cate sim­i­lar re­sults across these in­di­ca­tions, Sko­r­ney said, be­stow­ing the ther­a­py block­buster po­ten­tial.

CAR­DI­NAL is a Phase II/III tri­al — the mid-stage por­tion of the tri­al was un­veiled last year. On the safe­ty front, Rea­ta said the drug was well tol­er­at­ed showed a sim­i­lar safe­ty pro­file to the Phase II por­tion of the tri­al.

“Im­por­tant­ly, treat­ment emer­gent SAEs were ac­tu­al­ly worse for place­bo-treat­ed pa­tients. Con­cerns about flu­id over­load or MACE seem to be put to bed with this re­sult,” Sko­r­ney added.

Bar­dox­olone en­gages with the Keap1/Nrf2 path­way, which is piv­otal in the res­o­lu­tion of in­flam­ma­tion by sta­bi­liz­ing mi­to­chon­dr­i­al func­tion, restor­ing re­dox bal­ance, and sup­press­ing cy­tokine pro­duc­tion. In Oc­to­ber, Ab­b­Vie re­lin­quished its li­cense to Rea­ta’s omavelox­olone, bar­dox­olone and oth­er Nrf2 ac­ti­va­tors in a $330 mil­lion deal.

Amarin CEO John Thero discussing the company's plans for Vascepa, August 2019 — via Bloomberg

Amarin wins a block­buster ap­proval from the FDA. Now every­one can shift fo­cus to the patent

For all those people who could never quite believe that Amarin $AMRN would get an expanded label with blockbuster implications, the stress and anxiety on display right up to the last minute on Twitter can now end. But new, pressing questions will immediately surface now that the OK has come through.

On Friday afternoon, the FDA stamped its landmark approval on the industrial strength fish oil for reducing cardio risks for a large and well defined population of patients. The approval doesn’t give Amarin everything it wants in expanding its use, losing out on the primary prevention group, but it goes a long way to doing what the company needed to make a major splash. The approval was cited for patients with “elevated triglyceride levels (a type of fat in the blood) of 150 milligrams per deciliter or higher. Patients must also have either established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease.”

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Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Sarep­ta was stunned by the re­jec­tion of Vyondys 53. Now it's stun­ning every­one with a sur­prise ac­cel­er­at­ed ap­proval

Sarepta has a friend in the FDA after all. Four months after the agency determined that it would be wrong to give Sarepta an accelerated approval for their Duchenne MD drug golodirsen, regulators have executed a stunning about face and offered the biotech a quick green light in any case.

It was the agency that first put out the news late Thursday, announcing that Duchenne MD patients with a mutation amenable to exon 53 skipping will now have their first targeted treatment: Vyondys 53, or golodirsen. Having secured the OK via a dispute resolution mechanism, the biotech said the new drug has been priced on par with their only other marketed drug, Exondys 51 — which for an average patient costs about $300,000 per year, but since pricing is based on weight, that sticker price can even cross $1 million.

Sarepta shares $SRPT surged 23% after-market to $124.

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Paul Biondi (File photo)

Paul Biondi's track record at Bris­tol-My­ers cov­ered bil­lions in deals of every shape and size. Here's the com­plete break­down

Paul Biondi was never afraid to bet big during his stint as business development chief at Bristol-Myers Squibb. And while the gambles didn’t all pay out, by any means, his roster of pacts illustrates the broad ambitions the pharma giant has had over the last 5 years — capped by the $74 billion Celgene buyout.

On Thursday, we learned that Biondi had exited the company. And Chris Dokomajilar at DealForma came up with the complete breakdown on every buyout, licensing pact and product purchase Bristol-Myers forged during his tenure in charge of the BD team at one of the busiest companies in biopharma.

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Arie Belldegrun (Photo: Jeff Rumans for Endpoints News)

Ju­ry finds Gilead li­able for $585M and big roy­al­ties in Kite CAR-T patent case

A Kite deal that’s already become a burden on Gilead’s back just got heavier as a California jury has ruled Gilead must pay Bristol-Myers Squibb and Sloan Kettering $585 million plus a 27.6% royalty for patent infringement committed by its subsidiary. The ruling is almost certain to be appealed.

Kite Pharma — founded by Arie Belldegrun, now focused on a next-gen CAR-T company — has been facing a lawsuit since the day its first CAR–T therapy won approval in October, 2017. Juno Therapeutics and Sloan Kettering filed a complaint saying Kite had copied its technology. Gilead acquired Kite in June of that year for $11.9 billion.  Juno was acquired the following year by Celgene for $9 billion, before Celgene was acquired by Bristol-Myers Squibb in 2019.

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FDA ex­pert pan­el unan­i­mous­ly rec­om­mends ap­proval for Hori­zon Ther­a­peu­tics eye drug

An FDA advisory committee noted with concern a small safety database but unanimously endorsed a Horizon Therapeutics drug for a rare eye autoimmune disease that can blind patients: teprotumumab for thyroid eye disease (TED).

“It was a pretty easy vote,” said Erica Brittain, an NIH biostatistician and one of the 12 panelists on FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee.

This image shows a lab technician measuring the zone of inhibition during an antibiotic sensitivity test, 1972. The zone of inhibition is measured and compared to a standard in order to determine if an antibiotic is effective in treating the bacterial infection. (Gilda Jones/CDC via Getty Images)

Bio­phar­ma has aban­doned an­tibi­ot­ic de­vel­op­ment. Here’s why we did, too.

Timing is Everything
When we launched Octagon Therapeutics in late 2017, I was convinced that the time was right for a new antibiotic discovery venture. The company was founded on impressive academic pedigree and the management team had known each other for years. Our first program was based on a compelling approach to targeting central metabolism in the most dangerous bacterial pathogens. We had already shown a high level of efficacy in animal infection models and knew our drug was safe in humans.

Shehnaaz Suli­man dives back in­to Alzheimer's at Alec­tor; Pyx­is re­cruits Spring­Works founder Lara Sul­li­van as CEO

Amid Shehnaaz Suliman’s lengthy resume it could be easy to miss her stint leading early-stage Alzheimer’s R&D at Genentech, where she oversaw a program for the ill-fated crenezumab and initiated one of the first prevention studies around the devastating neurodegenerative disease. But it is this experience that she — after thinking long and hard about her next career move over the past months — will be leaning heavily on as the first president and COO of Alector.

PhII fail­ure in rare neu­rode­gen­er­a­tive dis­ease? No mat­ter, Bio­gen will mo­tor on in Alzheimer's

Biogen’s fierce focus on disorders of the brain has hit another roadblock.

On Friday, the US drugmaker — which recently resurrected its amyloid-targeting Alzheimer’s drug, aducanumab — said its anti-tau drug, gosuranemab, failed a mid-stage study in patients with progressive supranuclear palsy (PSP), a rare brain disorder that results from deterioration of brain cells that control movement and thought.