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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Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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David Hung (file photo)

Mas­ter deal­mak­er David Hung re­tools a SPAC sedan in­to a fi­nanc­ing mus­cle ve­hi­cle that leaves his can­cer start­up with $850M and a place on Wall Street

It’s only right that one of the industry’s top dealmakers just completed one of the biggest SPAC-related deals in the pipeline.

David Hung, of Medivation fame, has completed a back flip into the market, merging with EcoR1 Capital’s SPAC Panacea and landing neatly on Wall Street with an $NUVB stock ticker after filling out the blank check in his name. In addition to the $144 million held in the SPAC — provided none of the investors opt out — Hung is getting ahold of $500 million more being chipped in by a slate of institutional investors who feel that Hung could have the keys to another Medivation-style success.

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Lit­tle Zosano takes an­oth­er beat­ing as the FDA slaps down their ap­pli­ca­tion for a mi­graine patch

Zosano $ZSAN has officially come up short in its bid to develop a migraine patch.

The FDA rejected the company’s application to repurpose the triptan zolmitriptan in a new delivery system as Qtrypta, Zosano said Wednesday morning, issuing a CRL for the microneedle patch. Regulators cited inconsistent exposure levels across multiple clinical trials as the main reason for the thumbs down.

Investors did not take too kindly to the news, with Zosano shares plunking down around 25%. The company is requesting a Type A meeting to “provide clarity on the next steps for the program,” CEO Steven Lo said in a statement.

Pfizer CEO Albert Bourla (Drew Angerer/Getty Images)

Pfiz­er is on the verge of claim­ing a multi­bil­lion-dol­lar first-mover ad­van­tage with their Covid-19 vac­cine — an­a­lyst

From the beginning, Pfizer CEO Albert Bourla eschewed government funding for his Covid-19 vaccine work with BioNTech, willing to take all the $2 billion-plus risk of a lightning-fast development campaign in exchange for all the rewards that could fall its way with success. And now that the pharma giant has seized a solid lead in the race to the market, those rewards loom large.

SVB Leerink’s Geoff Porges has been running the numbers on Pfizer’s vaccine, the mRNA BNT162b2 program that the German biotech partnered on. And he sees a $3.5 billion peak in windfall revenue next year alone. Even after the pandemic is brought to heel, though, Porges sees a continuing blockbuster role for this vaccine as people around the world look to guard against a new, thoroughly endemic virus that will pose a permanent threat.

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UP­DAT­ED: CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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UP­DAT­ED: Brazil­ian vol­un­teer in As­traZeneca Covid-19 vac­cine tri­al has died in the place­bo arm — re­ports

A volunteer in AstraZeneca’s Covid-19 vaccine trial in Brazil has died, Brazilian health authorities said Wednesday, triggering fresh alarms over the future of the Oxford program. But later reports noted that the death was in the placebo group and AstraZeneca issued word that there were no concerns about continuing the study.

The Brazilian health agency Anvisa said it had received data from an investigation into the issue, per a Reuters report. The report was then updated citing a Brazilian newspaper with unnamed sources saying that the volunteer was in the placebo arm of the trial.