Putting the safe­ty is­sue to bed, Au­rini­a's late-stage lu­pus nephri­tis da­ta shines

Af­ter a check­ered mid-stage pro­gram marred by pa­tient deaths, Au­rinia emerged vic­to­ri­ous on Wednes­day with Phase III lu­pus nephri­tis da­ta that demon­strat­ed its lead drug is safe and ef­fec­tive for a pa­tient pop­u­la­tion that has few op­tions.

Pe­ter Green­leaf CEO, Au­rinia

Au­rinia’s shares sky­rock­et­ed in Thurs­day morn­ing pre­mar­ket trad­ing, as the Cana­di­an biotech un­veiled plans to sub­mit a mar­ket­ing ap­pli­ca­tion next year.

The 357-pa­tient place­bo-con­trolled AU­RO­RA tri­al test­ed the com­pa­ny’s drug, vo­closporin, in com­bi­na­tion with my­cophe­no­late and low-dose cor­ti­cos­teroids to eval­u­ate whether the ther­a­py could im­prove the speed of and over­all re­nal re­sponse rates in pa­tients with lu­pus nephri­tis, where the au­toim­mune dis­ease rav­ages the kid­neys, trig­ger­ing in­flam­ma­tion that could lead to blood and/or pro­tein in the urine, high blood pres­sure, poor kid­ney func­tion, or kid­ney fail­ure.

Pa­tients giv­en vo­closporin record­ed re­nal re­sponse of 40.8%, while those on the con­trol arm ex­pe­ri­enced a rate of 22.5% — meet­ing the main goal of the study (p < 0.001) at 52 weeks. The Au­rinia ther­a­py al­so in­duced sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments across all pre­spec­i­fied sec­ondary end­points in­clud­ing re­nal re­sponse at 24 weeks, par­tial re­nal re­sponse at dif­fer­ent time points and time to achieve uri­nary pro­tein-to-cre­a­ti­nine ra­tio.

Source: Au­rinia

Click on the im­age to see the full-sized ver­sion

On the safe­ty side, vo­closporin da­ta was al­so de­ci­sive.

Six deaths oc­curred in the study, one in the vo­closporin arm and five in the con­trol group. Se­ri­ous ad­verse events were re­port­ed in 20.8% of vo­closporin pa­tients, ver­sus 21.3% in the con­trol arm.

In 2016, Au­rinia hit a ma­jor road­block with its vo­closporin pro­gram af­ter 13 deaths were record­ed in its phase IIb study – 10 in the low-dose arm, 2 in the high-dose arm and on­ly one in the con­trol group. How­ev­er, 40% of the 265 pa­tients in the study were en­rolled in sites in Asia, where treat­ment stan­dards are dif­fer­ent, Au­rinia had sug­gest­ed at the time.

On Wednes­day, SVB Leerink’s Joseph Schwartz sug­gest­ed Au­rinia’s lat­est da­ta was in-line with his “op­ti­mistic ex­pec­ta­tions.”

“AUPH has ac­cord­ing­ly avoid­ed prob­lem­at­ic sites in Ph.3 AU­RO­RA and to­day’s re­sult shows the fruits of that ef­fort,” he said. “With a clear mor­tal­i­ty ad­van­tage in fa­vor of vo­closporin treat­ment, we think the safe­ty con­tro­ver­sy will take a per­ma­nent back­seat for vo­closporin in lu­pus nephri­tis (LN).”

Au­rinia’s shares flew up 137% to $19.89 in pre­mar­ket trad­ing.

The sys­temic au­toim­mune dis­ease, in which the body’s im­mune sys­tem launch­es an at­tack on its own tis­sues and or­gans, af­fects about 1.5 mil­lion Amer­i­cans, ac­cord­ing to The Lu­pus Foun­da­tion of Amer­i­ca. Rough­ly 60% of lu­pus pa­tients de­vel­op lu­pus nephri­tis and 1 in 4 progress to end-stage re­nal dis­ease.

Lu­pus is a drug de­vel­op­er’s night­mare. In the last six decades, there has been just one FDA ap­proval, with the field re­sem­bling a grave­yard in re­cent years.  Last Oc­to­ber, UCB and Bio­gen’s an­ti-CD40L drug failed in a late-stage study, months af­ter Xen­cor and Sanofi’s Abl­ynx al­so con­ced­ed de­feat in their pro­grams. In Au­gust, how­ev­er, As­traZeneca of­fered a glim­mer of hope af­ter its drug, an­i­frol­um­ab, cleared a Phase III study.

The on­ly bi­o­log­ic so far to win ap­proval for lu­pus is GSK’s Benlysta — which was cleared for adult use in 2011 and for rare cas­es of child­hood lu­pus this year. GSK is in the midst of test­ing Benlysta in com­bi­na­tion with Roche’s rit­ux­imab in the hope the com­bi­na­tion will have a more po­tent ef­fect on the dis­ease ver­sus Benlysta monother­a­py. And last month, Roche said it was work­ing on putting to­geth­er a late-stage study for its mon­o­clon­al an­ti­body Gazy­va in pa­tients with lu­pus nephri­tis.

Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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Covid-19 roundup: Left out no longer, No­vavax se­cures largest Warp Speed deal yet: $1.6B

It looks like Novavax won’t be left out of Operation Warp Speed after all.

A month after the Gaithersburg, MD biotech saw its shares tumble when it was left off the first reported list of finalists for the White House’s Covid-19 vaccine accelerator, HHS and the Department of Defense have announced a $1.6 billion deal to scale up their Covid-19 candidate. It is the largest deal HHS has announced yet, eclipsing the $1.2 billion deal the administration reached with AstraZeneca in May.

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Cel­lec­tis slammed af­ter pa­tient dies and FDA slaps a hold on their tri­al for an off-the-shelf CAR-T for mul­ti­ple myelo­ma

Cellectis was slammed after the market close on Monday as the biotech reported that the FDA demanded it hit the brakes on their MELANI-01 trial for their off-the-shelf cell therapy UCARTCS1A after one of the patients in the study died of treatment-related cardiac arrest.

The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Sec­ond PhI­II study for Idor­si­a's sleep drug re­turns pos­i­tive re­sults, but al­so rais­es new ques­tions

Following a successful Phase III study in April showcasing the safety and potential of its new sleep drug, Idorsia posted some mixed news in the second Phase III study, but that won’t stop a planned filing aimed at regulatory approval.

The drug, a dual orexin receptor antagonist (DORA) called daridorexant, was found to significantly improve sleep maintenance and subjective total sleep time in 25 mg doses, replicating results from the first Phase III study. However, improvements in sleep onset and daytime functioning narrowly missed statistical significance, despite numerical consistency with the April study.

UP­DAT­ED: Im­munomedics spells out PFS ben­e­fit of Trodelvy in mTNBC, hunt­ing a full OK just weeks af­ter ac­cel­er­at­ed ap­proval

By the time the FDA finally granted an accelerated OK for Immunomedics’ Trodelvy, we already got a very strong hint that their confirmatory Phase III study in metastatic triple-negative breast cancer was a success.

That’s because the independent data safety monitoring committee recommended that the trial be stopped early. But just what pointed them to the conclusion was still unclear.

“We do not know the totality of their decision other than it’s pretty evident that the primary endpoint was met; otherwise they could not request to halt the study,” Behzad Aghazadeh, the executive chairman, told Endpoints News at the time.

Shoshanna Shendelman, Applied Therapeutics CEO (Applied Therapeutics)

A lit­tle biotech slaps back at a 'crim­i­nal' short at­tack, vow­ing to pur­sue a pros­e­cu­tion of their case

As short attacks go, Biotech Research Partners’ assault on Applied Therapeutics’ “cherry picked” data and a variety of so-called red flags didn’t cause a whole lot of damage. Ahead of the July 4 holiday, its shares $APLT were dinged and showed signs of quick recovery.

But that didn’t stop an incendiary response, as the biotech swung into action bright and early Monday morning.

Applied Therapeutics accused the authors of the short report of manipulating graphs and figures, misrepresenting data and included factual misrepresentations — all of which added up, in their view, to fraud.

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Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

A boom­ing Drag­on­fly is tak­ing its TriN­KETs to Copen­hagen as the lat­est Bris­tol My­ers pact spurs ex­pan­sion plans — out­side the US

Bristol Myers Squibb is making a habit out of collaborating with the crew at Dragonfly, adding their 3rd deal in a series that now will take them into newly charted R&D territory. And the fast-growing team at the Cambridge-based biotech is adding a facility in Copenhagen for its next growth spurt, where the government is making it easy to recruit scientists internationally as the U.S. throttles back.

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Ernest Loumaye, ObsEva CEO (ObsEva)

UP­DAT­ED: Ob­sE­va’s sec­ond uter­ine fi­broids PhI­II comes through, send­ing some in­vestors to the hills

In the three-company race to develop a new uterine fibroid treatment, ObsEva long lagged behind AbbVie and Myovant. Still, they hoped that better efficacy — including a 93.9% response rate in one Phase III trial — could ultimately deliver better sales.

Now, though, the second of those Phase III studies is out, and it has brought the Swedish biotech back to earth.

In the second of their Phase III trials, 75.5% of patients who took ObsEva’s experimental tablet linzagolix plus a hormone saw their bleeding reduced by at least 50% and at least 80 ml after 24 weeks. Pooling those results with new data from their first Phase III trial — which showed a 93.9% response rate at 24 weeks and a 91.6% response rate at 52 weeks — ObsEva calculated a collective 84.7% responder rate for patients taking their therapy and said the data “confirm potential best-in-class” status.

Covid-19 roundup: Teamed up with NIH, Re­gen­eron launch­es PhI­II pre­ven­tion tri­al for an­ti­body cock­tail

As Regeneron moves its antibody cocktail into Phase II/III trials testing REGN-COV2 as a treatment for both hospitalized and non-hospitalized patients with Covid-19, the biotech is also starting a Phase III in the prevention setting.

The National Institute of Allergy and Infectious Diseases — which orchestrated the large, randomized study for remdesivir that produced positive results — will jointly run the study.

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