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.

Jeff Albers, Blueprint CEO

Di­ag­nos­tic champ Roche buys its way in­to the RET ti­tle fight with Eli Lil­ly, pay­ing $775M in cash to Blue­print

When Roche spelled out its original $1 billion deal — $45 million of that upfront — with Blueprint to discover targeted therapies against immunokinases, the biotech partner’s RET program was still preclinical. Four years later, pralsetinib is on the cusp of potential approval and the Swiss pharma giant is putting in much more to get in on the commercial game.

Roche gains rights to co-develop and co-commercialize the drug, with sole marketing responsibility for places outside the US and China (where CStone has staked its claim).

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Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

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Source: Shutterstock

Who are the women blaz­ing trails in bio­phar­ma R&D and lead­ing the fight against Covid-19? Nom­i­nate them for End­points' spe­cial re­port

One of the many inequalities the pandemic has laid bare is the gender imbalance in biomedical research. A paper examining Covid-19 research authorship wondered out loud: Where are the women?

It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.

Mene Pangalos, AstraZeneca R&D chief (AstraZeneca via YouTube)

A day af­ter Mod­er­na vac­cine re­sults, ru­mors swirl of pend­ing As­traZeneca da­ta

A day after Moderna and the NIH published much-anticipated data from their Phase I Covid-19 vaccine trial, attention is turning to AstraZeneca which, according to a UK report, is expected to publish its own early data tomorrow.

ITV’s Robert Peston reported that AstraZeneca will publish the Phase I data in The Lancet. 

AstraZeneca and Moderna represent the two most ambitious Covid-19 vaccine efforts, having set the quickest timelines for approval (though they were recently joined in that regard by the Pfizer-BioNTech partnership) and some of the loftiest goals in total doses. Yet there is even less known about AstraZeneca’s vaccine’s effect on humans than there was about Moderna’s before yesterday. Although, in a controversial move, Moderna released some statistics from its Phase I in May, AstraZeneca has yet to say anything about what it saw in its Phase I trial — a move consistent with the scientific convention to withhold data until it can be published in a peer-reviewed journal.

Ludwig Hantson, Alexion CEO

Why pay $4B for a steady di­et of dis­ap­point­ment? Porges turns thumbs down on Alex­ion’s M&A strat­e­gy, of­fers some point­ers

When Alexion announced recently that it was paying $1.4 billion to bag Portola and its underperforming Factor Xa inhibitor reversal agent, you could hear the head-scratching going on around virtual Wall Street.

Why was Alexion going down the discount lane for new products? And why something like this? Analysts have been urging Alexion to get serious about M&A for years if it was serious about diversifying the company beyond Soliris and its successor drug. But this wasn’t the kind of heavy-impact deal they were looking for.

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Mil­li­pore­Sig­ma to build new $20 mil­lion, 12,000-square-foot lab in Switzer­land

On the heels of opening a new laboratory in Shanghai last week, MilliporeSigma is continuing its construction push.

The Merck KGgA life science subsidiary announced Wednesday its intentions to build a new $20 million lab in Buchs, Switzerland to support its reference materials business. It’s estimated that the new facility will be completed in December 2021 and open in early 2022 and is expected to be 12,000 square feet.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

‘Plan­ning to vac­ci­nate every­one in the US,’ Mod­er­na out­lines ef­forts to sup­ply their Covid-19 vac­cine as man­u­fac­tur­ing ramps up ahead of PhI­II

Twelve days from the planned start of their Phase III pivotal trial, the executive crew at Moderna has set up the manufacturing base needed to begin production of the first 500,000 doses of their Covid-19 vaccine with plans to feed it into a global supply chain. But the initial batches will likely be ready in the US first, where company CEO Stéphane Bancel plans to be able to vaccinate everyone.

“We have started making commercial product at-risk, and will continue to do so every day and every week of the month,” Bancel told analysts during their morning call on the Phase I data just published in the New England Journal of Medicine.

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Covid-19 roundup: Vac­cine by end of 2020? Ken Fra­zier warns hype do­ing 'grave dis­ser­vice'

When it comes to setting expectations about a Covid-19 vaccine, Ken Frazier does not mince words.

Over a month after first casting doubts on the aggressive 12- to 18-month timeframe championed by the US government and his biopharma peers, the Merck CEO again cautioned against any hype around a quick vaccine approval.

In a wide-ranging interview with Harvard Business School professor Tsedal Neeley that touched other big topics such as race, Frazier emphasized that vaccines take a long time to develop. He would know: Out of the seven new vaccines introduced around the world in the past 25 years, four came from Merck.

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