De­sert­ed by Astel­las and Mer­ck, lit­tle Cor­re­vio still can't win over FDA pan­el con­cerned with its AFib drug's safe­ty

When the FDA spurned Astel­las’ pitch for atri­al fib­ril­la­tion drug ver­nakalant in 2008, reg­u­la­tors made it abun­dant­ly clear that it wasn’t the ef­fi­ca­cy they had a prob­lem with — two Phase III tri­als had shown the drug suc­cess­ful­ly re­stored 52% of pa­tients’ heart­beat from ir­reg­u­lar to nor­mal — but the car­dio safe­ty is­sues for a drug that was to com­pete with well es­tab­lished, low-risk op­tions. One li­cens­ing deal, one clin­i­cal hold and sev­er­al stud­ies lat­er, the chances of ap­proval aren’t look­ing any bet­ter.

Ex­perts on the agency’s Car­dio­vas­cu­lar and Re­nal Drugs Ad­vi­so­ry Com­mit­tee vot­ed 11-2 against ap­prov­ing the drug, deal­ing a fresh blow to its mak­er, Cor­re­vio Phar­ma. The pan­el large­ly agreed with the FDA in­ter­nal re­view that con­clud­ed the ben­e­fits didn’t out­weigh the risks, rais­ing is­sues such as low blood pres­sure, ar­rhyth­mias in the ven­tri­cles and even death.

Mark Cor­ri­g­an

Cor­re­vio, which mar­kets ver­nakalant as Brinavess in its na­tive Cana­da, Eu­rope and sev­er­al oth­er coun­tries, saw its stock $CORV sink be­low the $1 mark af­ter plum­met­ing 55%.

“We are dis­ap­point­ed with to­day’s out­come be­cause we be­lieve in the strength of the da­ta we pre­sent­ed to­day for Brinavess,” CEO Mark Cor­ri­g­an said in a state­ment. “The treat­ment land­scape is cur­rent­ly miss­ing a rapid, ef­fi­ca­cious and well tol­er­at­ed op­tion to treat pa­tients with re­cent on­set atri­al fib­ril­la­tion and we be­lieve Brinavess has the po­ten­tial to fill that un­met med­ical need.”

It had tak­en Cor­re­vio a decade to get here. In re­sponse to the FDA’s re­jec­tion in 2008 — which ac­tu­al­ly fol­lowed a refuse-to-file let­ter two years pri­or — the biotech, then known as Car­diome, planned and start­ed a new Phase III tri­al, ACT V. But in 2010, a case of car­dio­vas­cu­lar col­lapse with pulse­less elec­tri­cal ac­tiv­i­ty even­tu­al­ly lead­ing to death trig­gered a full clin­i­cal hold on that study.

Mer­ck, which had li­censed rights to the oral ver­sion of ver­nakalant ear­li­er, took over the IV side too for a short while, on­ly to have its ap­pli­ca­tion to re­move the hold and pro­posed mod­i­fi­ca­tions slammed by reg­u­la­tors. The FDA’s con­clu­sion:

We do not be­lieve that you have iden­ti­fied ei­ther a de­fin­i­tive mech­a­nism or root cause of these episodes of ver­nakalant-in­duced se­vere hy­poten­sion and/or clin­i­cal shock and do not be­lieve that your pro­posed mod­i­fi­ca­tions to the el­i­gi­bil­i­ty cri­te­ria are ad­e­quate to as­sure that such events will not re­cur in an­oth­er tri­al.

The team that is now Cor­re­vio has since con­duct­ed mul­ti­ple an­i­mal stud­ies in at­tempts to un­der­stand what’s go­ing on and find a sat­is­fy­ing mit­i­ga­tion strat­e­gy — in vain.

“(T)he hold re­mains in place at this time,” the FDA re­view­ers not­ed in their dossier ahead of the ad­comm.

Al­so pack­aged in the NDA were da­ta from post­mar­ket­ing stud­ies done out­side the US, par­tic­u­lar­ly an EU tri­al dubbed SPEC­TRUM, in which the treat­ment con­vert­ed 70.2% of AFib pa­tients in­to nor­mal si­nus rhythm, with a me­di­an to con­ver­sion time of 12 min­utes.

But the FDA still not­ed a to­tal of 174 se­ri­ous ad­verse drug re­ac­tions and five deaths. And some mem­bers of the pan­el point­ed out that giv­en the pa­tients in the tri­als were at low risk of de­vel­op­ing com­pli­ca­tions, there didn’t seem to be a con­vinc­ing way to pre­dict who needs spe­cial mon­i­tor­ing for safe­ty is­sues.

“It clear­ly has ben­e­fit but it does have risk,” said Bar­ry Davis of the Uni­ver­si­ty of Texas School of Pub­lic Health, who vot­ed against the drug, per Reuters. “If this were the on­ly drug or treat­ment around, yes, but there are oth­er op­tions.”

In ad­di­tion to med­ica­tion such as fle­cainide, dofetilide, propafenone and ibu­tilide, physi­cians may al­so pre­scribe elec­tri­cal car­diover­sion — if they de­cide an in­ter­ven­tion is need­ed at all.

There is still a pos­si­bil­i­ty — no mat­ter how slim — that the FDA will over­ride the ad­comm’s rec­om­men­da­tion and OK the drug. The fi­nal de­ci­sion will be hand­ed down by De­cem­ber 24.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA buck­les un­der the strain of a pan­dem­ic work­load, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

Pal­la­dio bags $20 mil­lion Se­ries B to top­ple a prob­lem­at­ic kid­ney dis­ease drug

Palladio Biosciences just took one step further in its quest to topple Otsuka’s Samsca with its own — it hopes safer — autosomal dominant polycystic kidney disease (ADPKD) drug.

The Pennsylvania-based biotech announced a $20 million Series B on Friday, which will fund a 10-person Phase III trial of its vasopressin V2 receptor agonist, lixivaptan. CEO Alex Martin expects to read out data in the first half of next year, then launch straight into a larger pivotal Phase III study with about 1,200 participants.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust in the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.

Laura Shawver (Silverback Therapeutics)

Fol­low­ing a hefty Se­ries B, Sil­ver­back Ther­a­peu­tics quick­ly pulls in $85M for 'an im­por­tant growth phase'

Months after reeling in a $78 million Series B round, Silverback Therapeutics has hooked an even larger Series C.

The Seattle-based company announced Wednesday that it netted $85 million from a slate of new and previous investors. The quick boost could be a sign that an IPO is on the way.

In an email, Silverback CEO Laura Shawver told me she was “not able to provide any additional comments about Silverback” beyond what was shared in the company’s news release. In the prepared statement, she said the company is at “an important growth phase.”