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.

Jake Van Naarden, Josh Bilenker, Nisha Nanda (Credit: Loxo, Aisling Capital)

Josh Bilenker and his Loxo crew are tak­ing the reins on on­col­o­gy R&D at Eli Lil­ly, culling the weak and map­ping a new path

Josh Bilenker, Jake Van Naarden and Nisha Nanda came out of Eli Lilly’s $8 billion Loxo Oncology buyout with a bundle of cash and plenty of choices on what they could do next. Start a new company, go public. Live on the beach in 5-star luxury. Contemplate the stars — in their own observatory.

So what are they doing?

They formed a new executive team that is taking over the management of Eli Lilly’s hundreds-strong oncology R&D group — essentially using Loxo as a base for a bold new experiment in Big Pharma R&D in an attempt to create a true biotech environment with the deep pockets of a top-15 industry player. They’ve recruited David Hyman from Memorial Sloan Kettering to join the team as chief medical officer. And the mandate includes culling out the oncology pipeline, highlighting their star prospects and going after new programs wherever they can find the best prospects.

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One of Wall Street’s most high-pro­file hedge funds push­es Alex­ion's CEO to the auc­tion block — and he's not budg­ing

Fresh off buying Barnes & Noble and prodding AT&T with some heavy-handed criticism after picking up a $3.2 billion stake in the company, the activist — and supremely high profile — hedge fund Elliott Management has stepped up with some M&A advice for Alexion’s management team.
And the execs on the team $ALXN are giving them a polite — but very firm — stiff arm Friday morning.
In a release out early Friday, the big biotech said that the Elliott team had been in touch to encourage them to sell the company. But that’s not on the agenda.

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Un­lock the full End­points ex­pe­ri­ence for your com­pa­ny — and sup­port our mis­sion of in­de­pen­dent bio­phar­ma re­port­ing

I want to give readers a quick update on the most important part of our business model — premium subscriptions. We have some crucial financial goals we hope to achieve by the end of the year, and the team here in Lawrence is ready to ship some swag to kick off this limited December promotion.

We offer two premium plans — Enterprise for companies ($1,000/year, unlimited people), and Insider for individuals ($200/year). This month of December will be the last chance to enroll at the original rates — which have remained flat since we launched them in 2017.

Jasper Ther­a­peu­tics launch­es out of Stan­ford with new ap­proach to stem cell treat­ment

The first girl in the trial came in with chronic diarrhea and the immune system of an untreated HIV patient. Born with a rare genetic disease that impeded her ability to make B and T cells, she had once been given a stem cell transplant but it didn’t take.  Back in the hospital, she was injected with a new experimental antibody and then given a new stem cell transplant. Soon, she gained weight. The diarrhea stopped.

Samantha Budd Haeberlein. Biogen via YouTube

UP­DAT­ED: Skep­tics pounce as Bio­gen de­tails pos­i­tive sub­group analy­sis on ad­u­canum­ab — and both sides are dig­ging in

“Exhilarating.” “A major advance.” “A milestone achievement.” If one had just tuned into the panel comments on Biogen’s presentation at CTAD, it would seem that the biotech had an impressive, disease-modifying Alzheimer’s drug in aducanumab.

But off the stage, reactions to their admittedly complicated dataset and the biotech’s explanation for resurrecting a drug that failed its futility analysis were a lot more mixed, with analysts continuing to question whether the evidence is substantial enough to warrant an FDA approval and raising new doubts on the safety side.

In an investor call later in the day, execs noted that they are not planning another study and stood by their intention, publicized in October to much surprise, to submit regulatory filings based on what they have.

“We don’t file willy nilly,” said Al Sandrock, head of R&D. “We only go to filing when we believe that there is a benefit-risk argument based on science, based on data. And if you look at our history, we haven’t done filings right and left without good reason.”

Biogen had a theory going into the Clinical Trials on Alzheimer’s Disease meeting.

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No­var­tis CEO Vas Narasimhan's R&D up­date spot­lights next wave of drug stars as well as late-stage fa­vorites

As one of the biggest spenders in biopharma R&D, Novartis execs love to tout the scope of its late-stage pipeline, spotlighting the winners most likely to create blockbuster revenue streams in the near future.

Building on the 5 drug approvals the pharma giant expects to end the year with, Novartis CEO Vas Narasimhan — who’s done a slate of acquisitions topped by the recent $9.7 billion MedCo buyout — tapped the top emerging drugs as:

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Jeff Jonas, Sage

UP­DAT­ED: Sage's star ex­per­i­men­tal de­pres­sion drug fails the cru­cial MOUN­TAIN study — shares crash

Sage Therapeutics’ crucial MOUNTAIN study for Sage-217 has failed, setting the stage for a quick and ugly investor backlash.

Widely viewed by analysts as the critical clinical study $SAGE needed to win on major depression, researchers say the drug failed to beat out a placebo at day 15, falling well short of the mark for statistical significance on the primary endpoint. And investors reacted with alacrity, fleeing the stock and gutting the price with a 60% instantaneous drop — erasing about $4.6 billion in market cap in an instant.

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Ex-Cel­gene ex­ec Ter­rie Cur­ran puts her Phath­om team in place; Car­away taps Mar­tin Williams as CEO

→ Gastrointestinal disease-focused Phathom Pharmaceuticals has shaken up its leadership team. The company has tapped former Celgene exec Terrie Curran as CEO, succeeding David Socks, who is transitioning to interim CFO. Curran was president of Celgene’s global inflammation and immunology franchise — helping with the sale of Otezla for $13.4 billion to Amgen — and has held a previous stint at Merck. In addition to Curran, the company also welcomed former Omeros CMO Eckhard Leifke as CMO, ex-Celgene exec Joseph Hand as chief administrative officer, and former general counsel for Cyclerion Therapeutics Larry Miller as general counsel. They also replaced Chris Slavinsky on the board with Takeda exec Asit Parikh.

UCB buffs up in block­buster pso­ri­a­sis race as bimek­izum­ab beats Hu­mi­ra in head-to-head

Just weeks after boasting head-to-head victories over first placebo and then J&J’s IL-23 contender Stelara in clearing psoriasis, the results are in for UCB’s last Phase III trial, in which bimekizumab went up against the world’s best-selling drug.

Only topline results are provided for today’s readout of the BE SURE study, so we won’t find out just how superior bimekizumab proved against Humira on the co-primary endpoints — standard scores known as PASI90 and IGA measuring the impact and severity of the disease — until a scientific conference in 2020.