Fast on Glax­o­SmithK­line's heels, Au­rinia wins OK to steer a sec­ond lu­pus nephri­tis drug straight to the mar­ket

Glax­o­SmithK­line’s Benlysta isn’t alone in the small cir­cle of ap­proved lu­pus nephri­tis drugs any­more.

Lit­tle Au­rinia Phar­ma­ceu­ti­cals has got­ten the green light from the FDA to start mar­ket­ing its first and on­ly pro­gram, vo­closporin, un­der the brand name Lup­ky­nis — some­thing CEO Pe­ter Green­leaf says it’s been ready to do since De­cem­ber.

Reg­u­la­tors went right down to the wire on the de­ci­sion, keep­ing the com­pa­ny and the en­tire sales­force it’s al­ready as­sem­bled on its toes.

Pe­ter Green­leaf

But they haven’t been idle. In an ear­li­er in­ter­view, Green­leaf told End­points News that the field team, which to­tals about 100 to 150 sales reps, has al­ready start­ed talk­ing to physi­cians about LN and go­ing to med­ical meet­ings to present da­ta on vo­closporin. By block­ing cal­cineurin, a sig­nal­ing pro­tein in­volved in T cell ac­ti­va­tion, the small mol­e­cule oral drug is de­signed to in­hib­it IL-2 and tamps down in­flam­ma­tion in the kid­ney.

The Phase III tri­al, AU­RO­RA, vo­closporin plus my­cophe­no­late mofetil and low-dose cor­ti­cos­teroids hit the pri­ma­ry end­point on re­nal re­sponse at 1-year. It al­so hit the bar for get­ting pro­tein­uria, a mea­sure­ment of ac­tive dis­ease, un­der con­trol.

“I mean, that’s the num­ber 1 treat­ment goal that physi­cians search for,” Green­leaf said.

First an­nounced in late 2019, those re­sults were sev­en years in the mak­ing for CMO Neil Solomons, who was part of a team at Vi­for Phar­ma that brought in vo­closporin from Isotech­ni­ka — it was be­ing de­vel­oped for kid­ney trans­plant re­jec­tion at that time — and spun out Au­rinia. Even though a pre­vi­ous study he was in­volved in had ce­ment­ed my­cophe­no­late mofetil, or MMF, among oth­er un­ap­proved meds as the stan­dard of care, there was re­al­ly no di­rect ev­i­dence of their treat­ment ef­fect (They were al­so “high­ly tox­ic,” ac­cord­ing to a tri­al in­ves­ti­ga­tor.)

Neil Solomons

“We’re the first com­pa­ny to do that,” Solomons said, “ran­dom­ized blind­ed con­trolled study with our Phase II tri­al back in 2016 to ac­tu­al­ly demon­strate that the drug ac­tu­al­ly tru­ly works in this area.“

Al­so among the firsts: a patent­ed dos­ing pro­to­col that al­lows pa­tients to titrate down the dose based on an es­ti­mate of re­nal func­tion known as eGFR, and re­duc­tion of cor­ti­cos­teroids re­quired in the reg­i­men.

All of those qual­i­ties, the com­pa­ny reck­ons, could give its reps plen­ty to con­vince doc­tors to take on their drug.

Green­leaf added that vo­closporin “works very very rapid­ly,” show­ing ben­e­fit at both the 6-month and 1-year time points that seems com­pa­ra­ble to — with the usu­al caveats about cross-tri­al com­par­isons — what Benlysta, a bi­o­log­ic, showed at 2 years.

“Who knows what that means for fu­ture treat­ment — how they’re used along­side of each oth­er, in con­cert or with­in the full treat­ment con­tin­u­um,” the CEO, who’s run a trio of oth­er biotechs af­ter leav­ing As­traZeneca’s Med­Im­mune, said. “But to­day as it ex­ists we think our drug stands very well on its own.”

By their count, the LN pa­tient pop­u­la­tion in the US is well north of 100,000. With $400 mil­lion in cash, Au­rinia’s $AUPH com­mer­cial team will have am­ple fund­ing for sev­er­al years. Ot­su­ka, its new part­ner, is tasked with scor­ing OKs and com­mer­cial­iz­ing in the EU, Japan and else­where.

Joseph Schwartz of SVB Leerink is a be­liev­er. While GSK may have the up­per hand at launch, he wrote, vo­closporin should even­tu­al­ly “come out on top, as it has su­pe­ri­or ef­fi­ca­cy as com­pared to Benlysta”: Au­rinia re­port­ed a re­nal re­sponse rate of 40.8% ver­sus 22.5% in the con­trol arm while Benlysta’s dif­fer­ence with con­trol was small­er (43% vs 32%).

For 2021, he’s mod­el­ing US sales at $87.6 mil­lion as­sum­ing a price of $35,000.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

What lured Hal Bar­ron away?; Top FDA minds on ac­cel­er­at­ed ap­proval re­forms; ‘Dead wrong’ Aduhelm ad blitz; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Nothing can really compete with Hal Barron’s departure from GlaxoSmithKline as the news of the week, but we do have plenty of original reporting and analysis from the Endpoints team in this edition. Enjoy and have a nice weekend.

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Mer­ck wins le­gal bat­tle over in­sur­ance cov­er­age af­ter ran­somware at­tack

Merck has emerged victorious from a years-long legal battle with insurers over the coverage of more than a billion dollars in losses from the malware NotPetya, with a New Jersey Superior Court judge concluding that the responsibility is on insurers to clarify their policies around cyber attacks.

The pharma giant was one of several victims of a global cyber attack back in 2017 that also hit Danish shipping company Maersk, American food company Mondelēz, French construction giant Saint-Gobain and even the systems monitoring the Chernobyl nuclear power stations, Bloomberg reported back in 2019.

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Crit­ics push back on Alzheimer’s As­so­ci­a­tion ad blitz to get Medicare to change its Aduhelm rul­ing: 'Dead wrong'

The latest Alzheimer’s Association advertising campaign encourages people to fight.

Not against the disease or for more research or treatments, but against the Centers for Medicare and Medicaid Services. More specifically, CMS’ recent reimbursement decision to only pay for Biogen and Eisai’s controversial Alzheimer’s drug Aduhelm for patients in clinical trials.

With CMS’ preliminary decision now in a 30-day comment period, patient advocates’ goal is to convince CMS to reverse its decision with a marketing blitz and public pressure.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Fail­ing to con­firm clin­i­cal ben­e­fit, Gilead pulls 2 ac­cel­er­at­ed ap­proval in­di­ca­tions for can­cer drug

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.

Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.