FDA ap­provals roundup: Zo­genix's Fin­tepla, Ul­tragenyx's Do­jolvi, and Genen­tech's Ph­es­go

A week­ly up­date on new drug ap­provals and in­di­ca­tions from the FDA:

New ap­provals

Fin­tepla gets the go-ahead for Dravet syn­drome

Zo­genix’s Fin­tepla (fen­flu­ramine) has been ap­proved for the treat­ment of seizures as­so­ci­at­ed with Dravet syn­drome in pa­tients aged 2 years or old­er. The syn­drome is a rare, life-threat­en­ing form of epilep­sy.

The ap­proval was based on find­ings from two clin­i­cal stud­ies in 202 par­tic­i­pants aged be­tween 2 and 18 years, in which the change from base­line in fre­quen­cy of con­vul­sive seizures was mea­sured. In both stud­ies, chil­dren who re­ceived Fin­tepla had sig­nif­i­cant­ly greater re­duc­tions in the fre­quen­cy of con­vul­sive seizures, com­pared with those re­ceiv­ing place­bo. The re­duc­tions were seen with­in 3-4 weeks of ther­a­py ini­ti­a­tion and re­mained gen­er­al­ly con­sis­tent dur­ing the treat­ment pe­ri­ods of 14-15 weeks.

Fin­tepla is a Sched­ule IV con­trolled sub­stance, car­ry­ing a boxed warn­ing that it is as­so­ci­at­ed with valvu­lar heart dis­ease and pul­monary ar­te­r­i­al hy­per­ten­sion. It is avail­able on­ly through a re­strict­ed drug dis­tri­b­u­tion pro­gram, un­der a risk eval­u­a­tion and mit­i­ga­tion strat­e­gy (REMS) stip­u­lat­ing that pre­scribers and pa­tients must com­ply with the re­quired car­diac mon­i­tor­ing with echocar­dio­grams to re­ceive the ther­a­py.

The ap­pli­ca­tion was grant­ed pri­or­i­ty re­view. The ther­a­py re­ceived or­phan drug des­ig­na­tion.

Do­jolvi picks up ap­proval for rare ge­net­ic dis­or­der

Ul­tragenyx’s Do­jolvi (tri­hep­tanoin) has been ap­proved for the treat­ment of pe­di­atric and adult pa­tients with mol­e­c­u­lar­ly con­firmed long-chain fat­ty acid ox­i­da­tion dis­or­ders (LC-FAOD).

LC-FAOD are a group of rare, life-threat­en­ing ge­net­ic dis­or­ders in which the body is not able to con­vert long-chain fat­ty acids in­to en­er­gy. Do­jolvi is a source of calo­ries and fat­ty acids for these pa­tients.

Safe­ty da­ta for the ther­a­py came from 79 pa­tients with LC-FAOD who re­ceived Do­jolvi in 2 stud­ies, an open-la­bel, 78-week study with 29 pa­tients (Study 1), fol­lowed by an open-la­bel ex­ten­sion study (Study 2). In all, 24 pa­tients from Study 1 con­tin­ued in­to Study 2. Pa­tients ranged in age from 4 months to 63 years. They re­ceived dai­ly dos­es of Do­jolvi for a mean du­ra­tion of 23 months. The most com­mon ad­verse re­ac­tions to the study drug in­clud­ed ab­dom­i­nal (60%), di­ar­rhea (44%), vom­it­ing (44%), and nau­sea (14%). A third study, a 4-month, dou­ble-blind, ran­dom­ized-con­trolled study re­port­ed ad­verse re­ac­tions sim­i­lar to those from the first two stud­ies.

The agency pre­vi­ous­ly grant­ed the ap­pli­ca­tion rare pe­di­atric dis­ease and fast track des­ig­na­tions. Ul­ti­mate­ly, it as­signed a stan­dard re­view des­ig­na­tion with a Pre­scrip­tion Drug User Fee Act tar­get date of Ju­ly 31.

New in­di­ca­tions

Ph­es­go com­bo OK’d for home ad­min­is­tra­tion for HER2+ breast can­cer

Genen­tech’s Ph­es­go (per­tuzum­ab, trastuzum­ab, and hyaluronidase–zzxf in­jec­tion) has been ap­proved as a ther­a­py for adult pa­tients with metasta­t­ic HER2-pos­i­tive breast can­cer and for adults with ear­ly HER2-pos­i­tive breast can­cer, based on the re­sults of FDA-ap­proved com­pan­ion di­ag­nos­tic test.

Ph­es­go is ini­tial­ly used in com­bi­na­tion with chemother­a­py and could con­tin­ue to be ad­min­is­tered at home by a qual­i­fied health care pro­fes­sion­al once the chemother­a­py reg­i­men is fin­ished.

The drug con­tains a fixed-dose com­bi­na­tion of per­tuzum­ab and trastuzum­ab with hyaluronidase. Its ap­proval was based on the re­sults of a non­in­fe­ri­or­i­ty study in pa­tients with HER2-pos­i­tive ear­ly breast can­cer show­ing that the drug’s ef­fi­ca­cy and safe­ty were com­pa­ra­ble with IV per­tuzum­ab and IV trastuzum­ab. Ad­min­is­tra­tion-re­lat­ed re­ac­tions were high­er with Ph­es­go be­cause of the sub­cu­ta­neous route of ad­min­is­tra­tion.

“As part of the FDA’s on­go­ing com­mit­ment to ad­dress the nov­el coro­n­avirus pan­dem­ic, we con­tin­ue to keep a strong fo­cus on pa­tients with can­cer who con­sti­tute a vul­ner­a­ble pop­u­la­tion at risk of con­tract­ing the dis­ease. At this crit­i­cal time, we con­tin­ue to ex­pe­dite on­col­o­gy prod­uct de­vel­op­ment. This ap­pli­ca­tion was ap­proved about four months ahead of the FDA goal date,” said Richard Paz­dur, di­rec­tor of the agency’s On­col­o­gy Cen­ter of Ex­cel­lence and act­ing di­rec­tor of the Of­fice of On­co­log­ic Dis­eases in the Cen­ter for Drug Eval­u­a­tion and Re­search.

Baven­cio gets new in­di­ca­tion for urothe­lial car­ci­no­ma

EMD Serono/Pfiz­er’s Baven­cio (avelum­ab) has re­ceived an ex­pand­ed in­di­ca­tion for main­te­nance treat­ment of pa­tients with lo­cal­ly ad­vanced or metasta­t­ic urothe­lial car­ci­no­ma (UC) that has not pro­gressed with first-line, plat­inum-con­tain­ing ther­a­py. It is the first ap­proved im­munother­a­py to show sig­nif­i­cant im­prove­ment in over­all sur­vival in the first-line set­ting.

The ap­pli­ca­tion orig­i­nal­ly re­ceived break­through ther­a­py des­ig­na­tion and was grant­ed pri­or­i­ty re­view, which was com­plet­ed un­der the re­al-time on­col­o­gy re­view.

The hu­man an­ti-pro­grammed death lig­and-1 an­ti­body has a pre­vi­ous ap­proval for lo­cal­ly ad­vanced or metasta­t­ic UC that has pro­gressed dur­ing or af­ter plat­inum-con­tain­ing chemother­a­py. It has al­so been ap­proved in com­bi­na­tion with ax­i­tinib for the first-line treat­ment of pa­tients with ad­vanced re­nal cell car­ci­no­ma, and for treat­ing Merkel cell car­ci­no­ma in adults and pe­di­atric pa­tients old­er than 12 years and old­er with metasta­t­ic dis­ease.

Keytru­da ex­pand­ed for in­cur­able CRC, cSCC

Mer­ck’s Keytru­da (pem­brolizum­ab) has re­ceived two ex­pand­ed in­di­ca­tions, one, as a first-line treat­ment for pa­tients with un­re­sectable or metasta­t­ic mi­crosatel­lite in­sta­bil­i­ty-high or mis­match re­pair de­fi­cient col­orec­tal can­cer, and a sec­ond, for treat­ing pa­tients with in­cur­able re­cur­rent or metasta­t­ic cu­ta­neous squa­mous cell car­ci­no­ma (cSCC).

The ap­proval for CRC was grant­ed less than a month af­ter the com­pa­ny sub­mit­ted a sup­ple­men­tal bi­o­log­ics li­cense ap­pli­ca­tion (sBLA) based on re­sults from the KEYNOTE-177 tri­al. It is the first sin­gle-agent, an­ti-PD-1 ther­a­py ap­proved as a first-line ther­a­py for these pa­tients.

The sBLA was re­viewed un­der the agency’s re­al-time on­col­o­gy re­view pi­lot pro­gram. Re­view was al­so done un­der Pro­ject Or­bis, which al­lows for con­cur­rent sub­mis­sion and re­view of on­col­o­gy drugs among in­ter­na­tion­al part­ners. For this ap­pli­ca­tion, the agency is col­lab­o­rat­ing with the Aus­tralian Ther­a­peu­tic Goods Ad­min­is­tra­tion, Health Cana­da and Swissmedic on their on­go­ing re­view of the ap­pli­ca­tion.

The ex­tend­ed ap­proval for cSCC was based on find­ings from the KEYNOTE-629 tri­al.


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UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Fi­bro­Gen shares skid low­er as a sur­prise ad­comm rais­es risks on roxa OK

FibroGen will likely have to delay its US rollout for roxadustat once again.

In an unexpected move, the FDA is convening its Cardiovascular and Renal Drugs Advisory Committee to review the NDA in an advisory committee meeting. The date is yet to be confirmed.

Just a few weeks ago, SVB Leerink analyst Geoffrey Porges predicted that the roxa approval could come ahead of the PDUFA date on March 20 — effusive despite already being let down once by the FDA’s extension of its review back in December. AstraZeneca, which is partnered with FibroGen on the chronic kidney disease-related anemia drug, disclosed regulators had requested further clarifying analyses of clinical data.

Michael Shpigelmacher

Khosla joins bet on un­con­ven­tion­al start­up look­ing to send drug de­liv­er­ing ro­bots in­to the brain

When Michael Shpigelmacher started the project, he knew he’d have to fund it himself. Every other effort of its kind was academic, rejected as too risky by investors.

Shpigelmacher, a robotics geek and entrepeneur who had drifted into consulting for pharma, wanted to build the real-life equivalent of technology from the 1960s film Fantastic Voyage, the one where a submarine crew is shrunk to “about the size of a microbe” and sent on a mission to repair a scientist’s brain. He scanned the literature, found the lab that was working on the most advanced project — at the Max Planck Institute in Germany, it turned out — and started funding them with money from his own account, along with some seed cash from friends and family.

UP­DAT­ED: Feds clear the road for J&J to start de­liv­er­ing mil­lions of dos­es of their Covid-19 vac­cine — but frets linger about run­ner-up sta­tus

All the pieces needed to trigger a third wave of Covid-19 vaccine supply to start washing over the US fell neatly into place over the weekend.

After providing for a brief mime of regulatory judiciousness, the FDA stamped their emergency approval on J&J’s Covid-19 vaccine Saturday, adding to the Biden administration’s plan aimed at ending the pandemic in the near term — at least in the US. The CDC came through on Sunday with its stamp of approval and J&J is reportedly expected to start delivering vaccine sometime in the next few days.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

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UP­DAT­ED: Biotech's shares rout­ed af­ter the FDA de­mands new tri­al, rais­es safe­ty and end­point is­sues in sur­prise CRL

A small biotech that’s been laboring long and hard on an oral chemo program for metastatic breast cancer was slammed hard on Monday morning, losing more than half of its market cap after revealing that the FDA had issued a surprise CRL with some harsh new hurdles in place.

Athenex $ATNX says that regulators stiff-armed its application for oral paclitaxel and encequidar — a marked setback after winning a priority review earlier that should have signified a more positive regulatory frame of mind. And Athenex was clear that any comeback for this program is going to face a high bar at the FDA.

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Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

Ab­b­Vie tees up a biotech buy­out af­ter siz­ing up their Parkin­son's drug spun out of Ke­van Shokat's lab

AbbVie has teed up a small but intriguing biotech buyout after looking over the preclinical work it’s been doing in Parkinson’s disease.

The company is called Mitokinin, a Bay Area biotech spun out of the lab of UCSF’s Kevan Shokat, whose scientific explorations have formed the academic basis of a slew of startups in the biotech hub. One of Shokat’s PhD students in the lab, Nicholas Hertz, co-founded Mitokinin using their lab work on PINK1 suggesting that amping up its activity could play an important role in regulating the mitochondrial dysfunction contributing to Parkinson’s disease pathogenesis and progression.

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Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

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