Em­maus re­scinds EU mar­ket­ing ap­pli­ca­tion, fol­low­ing neg­a­tive re­view

Two years ago, Em­maus Life Sci­ences se­cured FDA ap­proval for its sick­le cell dis­ease (SCD) ther­a­py — mark­ing the first new ap­proval for pa­tients af­fect­ed by the group of in­her­it­ed red blood cell dis­or­ders that typ­i­cal­ly af­flict those of African an­ces­try in two decades. But the Eu­ro­pean reg­u­la­tor was not sat­is­fied with the dataset sup­port­ing the ther­a­py  — prompt­ing its mak­er on Thurs­day to re­scind its ap­pli­ca­tion.

En­dari is a high­ly pu­ri­fied (phar­ma­ceu­ti­cal grade) ver­sion of the amino acid L-glu­t­a­mine and was ap­proved in Ju­ly 2017 to re­duce the se­vere com­pli­ca­tions that come with SCD. (Non-med­ical grade L-glu­t­a­mine is avail­able as a sup­ple­ment over the counter).

The US ap­proval was based large­ly on a 230-pa­tient place­bo-con­trolled study that ran for 48 weeks. Da­ta showed pa­tients on En­dari ex­pe­ri­enced 25% few­er sick­le cell crises, as well as a 33% drop in hos­pi­tal­iza­tions, com­pared to place­bo. Ad­di­tion­al­ly, pa­tients on En­dari spent few­er cu­mu­la­tive days in the hos­pi­tal and ex­pe­ri­enced a low­er in­ci­dence of acute chest syn­drome.

In its as­sess­ment, the Eu­ro­pean reg­u­la­tor took is­sue with the num­ber of dropouts in the study. The EMA’s Com­mit­tee for Med­i­c­i­nal Prod­ucts for Hu­man Use (CHMP) said the main study on the ther­a­py — chris­tened Xyn­dari in Eu­rope — did not show it was ef­fec­tive at re­duc­ing the num­ber of sick­le cell crises or hos­pi­tal vis­its, due to the high­er num­ber of dropouts in the drug arm.

“(I)nfor­ma­tion on how the med­i­cine worked for those pa­tients (who dropped out) was not avail­able. The CHMP con­sid­ered that the way da­ta from these pa­tients were dealt with was not ap­pro­pri­ate,” the agency said ear­li­er this year.

A to­tal of 156 pa­tients com­plet­ed the tri­al — 97 of 152 pa­tients (63.8%) in the L-glu­t­a­mine group and 59 of 78 pa­tients (75.6%) in the place­bo group, ac­cord­ing to da­ta pub­lished by Em­maus. “The rea­sons for dis­con­tin­u­a­tion were sim­i­lar in the two tri­al groups; the most com­mon rea­sons were with­draw­al of con­sent, ‘oth­er’ rea­sons, and non­ad­her­ence,” the com­pa­ny wrote.

The EMA went on to flag con­cern about a small study used to sup­port the ap­pli­ca­tion for the drug. Once again, many pa­tients in this study dropped out ear­ly, the reg­u­la­tor un­der­scored. “(I)n this study more of the pa­tients tak­ing Xyn­dari had re­ceived a med­i­cine for sick­le cell dis­ease called hy­drox­yurea than pa­tients tak­ing place­bo. This could have in­flu­enced the re­sults.”

Af­ter its ini­tial neg­a­tive rec­om­men­da­tion in May, Em­maus asked the EMA to re­view its da­ta again in June, but the reg­u­la­tor stood by its orig­i­nal stance.

On Thurs­day, Em­maus — which was delist­ed from the Nas­daq ear­li­er this month — dis­closed it was with­draw­ing its Eu­ro­pean mar­ket­ing ap­pli­ca­tion.

Yu­ta­ka Ni­ihara Busi­ness Wire

“Be­cause we have demon­strat­ed the ef­fi­ca­cy of Xyn­dari, as sup­port­ed by the da­ta from the tri­als con­duct­ed, we are dis­ap­point­ed in the CHMP’s po­si­tion,” chief Yu­ta­ka Ni­ihara said in a state­ment.

How­ev­er, Xyn­dari is cur­rent­ly sup­plied through ear­ly ac­cess pro­grams based on named pa­tient use in a num­ber of EU mem­ber states, Turkey and the Mid­dle East.

Mean­while, Em­maus’ ri­vals in the Unit­ed States are scram­bling to get their SCD prod­ucts on the mar­ket.

Glob­al Blood Ther­a­peu­tics $GBT un­veiled pos­i­tive piv­otal da­ta on its sick­le cell dis­ease drug in June — the once-dai­ly pill vox­elo­tor is de­signed to work by in­creas­ing he­mo­glo­bin’s affin­i­ty for oxy­gen. No­var­tis’ $NVS ther­a­py for the blood dis­or­der was grant­ed a speedy re­view by the FDA in Ju­ly — the mon­o­clon­al an­ti­body, called crizan­l­izum­ab,  is ad­min­is­tered in­tra­venous­ly and en­gi­neered to bind to a mol­e­cule called P-se­lectin, one of the ma­jor dri­vers of the va­so-oc­clu­sive process. Oth­er drug­mak­ers, in­clud­ing Blue­bird Bio, Imara, and part­ners CRISPR Ther­a­peu­tics and Ver­tex, are al­so work­ing on their own drugs.

Sick­le cell dis­ease pa­tients have atyp­i­cal he­mo­glo­bin mol­e­cules, which can dis­tort red blood cells in­to a sick­le, or cres­cent, shape. Symp­toms such as ane­mia, re­peat­ed in­fec­tions and pe­ri­od­ic episodes of pain called va­so-oc­clu­sive crises (VOC) when sick­le-shaped red blood cells get stuck in­side blood ves­sels be­gin to ap­pear in ear­ly child­hood. These episodes de­prive the body of oxy­gen-rich blood, which can cul­mi­nate in wide­spread tis­sue and or­gan dam­age — par­tic­u­lar­ly in the lungs, kid­neys, spleen, heart, and brain — and dras­ti­cal­ly di­min­ish life ex­pectan­cy.

For now, bone mar­row trans­plants of­fer the on­ly po­ten­tial cure for sick­le cell ane­mia — but the pro­ce­dure is not safe enough for pa­tients old­er than 16 — be­sides se­cur­ing a healthy donor is dif­fi­cult and the risks can be life-threat­en­ing. There­fore, treat­ment is typ­i­cal­ly lim­it­ed to avoid­ing crises, re­liev­ing symp­toms and pre­vent­ing com­pli­ca­tions. Hy­drox­yurea, a drug be­lieved to stim­u­late the pro­duc­tion of fe­tal he­mo­glo­bin, is of­ten giv­en dai­ly to re­duce the fre­quen­cy of painful crises — but it in­creas­es the risk of in­fec­tion, and the risks as­so­ci­at­ed with long-term use are un­clear.

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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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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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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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.

FDA lifts par­tial hold on ADC, clear­ing way for a 2021 read­out and two po­ten­tial near-term ap­provals

In throwing $267 million and a multi-billion dollar valuation at ADC Therapeutics for their May IPO, investors were betting that the partial hold the FDA had just placed on their second lead drug would prove immaterial. Time, it appears, has proven them right.

The FDA has lifted the partial hold, ADC said this morning. The move clears the way for an anticipated 2021 readout from their second pivotal study, a Phase II trial testing their experimental antibody drug conjugate camidanlumab tesirine, or Cami, in Hodgkin’s lymphoma.

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

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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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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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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.

Douglas Love, Annexon CEO (Annexon)

IPO bound? Ac­tu­al­ly, An­nex­on was al­ready prepped and primed to toss its S-1 to Wall Street as in­vestors ral­lied

The Wall Street IPO shuffle generally calls for a little distance between the crossover ante and the Wall Street double, but with the window on the street wide open and biotech sizzling hot, who’s waiting?

The crew at Annexon didn’t leave anyone in suspense for long about their IPO plans. A day after the Bay Area biotech with clinical plans to target neurodegeneration quietly unveiled a $100 million raise, they were back with an S-1 outlining a pitch to double that — or more.

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