FDA gives thumbs-down on hear­ing loss drug, cit­ing man­u­fac­tur­ing is­sues, and sends Fen­nec stock reel­ing

A small, North Car­oli­na-based biotech has run in­to some head­winds in its ef­forts to de­vel­op a com­pound that pre­vents hear­ing loss as­so­ci­at­ed with cis­platin chemother­a­py treat­ments.

The FDA hand­ed down a com­plete re­sponse let­ter to Fen­nec Phar­ma­ceu­ti­cals $FENC for its Ped­mark drug late Mon­day night, cit­ing man­u­fac­tur­ing is­sues with the com­pa­ny’s sup­pli­er. Fen­nec hopes to meet with reg­u­la­tors some­time with­in the next month or two, CEO Ros­ty Raykov said in a call with in­vestors Tues­day morn­ing, in or­der to re­solve the is­sue.

Raykov fur­ther em­pha­sized dur­ing the call that there were no clin­i­cal safe­ty or ef­fi­ca­cy prob­lems and an ad­di­tion­al tri­al was not re­quired.

Nonethe­less, the news rat­tled Wall Street, as the biotech’s stock was down more than 35% in morn­ing trad­ing.

Per Raykov, Fen­nec re­ceived a Form 483 from the agency, which list­ed con­di­tions or prac­tices that are re­quired to be re­solved pri­or to Ped­mark’s ap­proval. When asked by in­vestors what specif­i­cal­ly need­ed to be fixed, Raykov de­murred and re­it­er­at­ed that there were no safe­ty is­sues.

Though the com­pa­ny’s goal is to meet with the FDA some­time soon, Raykov couldn’t pro­vide an ex­act time­line due to the CRL be­ing is­sued late last night, he said, and Fen­nec is still hash­ing out a plan.

De­spite the is­sues cit­ed Mon­day night, Fen­nec is not plan­ning on switch­ing man­u­fac­tur­ers, Raykov said. Giv­en that the same fa­cil­i­ty pro­duces planned Ped­mark batch­es for both the Amer­i­can and Eu­ro­pean mar­kets, Fen­nec aims to iron out the headaches as quick­ly as pos­si­ble. Fen­nec’s Eu­ro­pean ap­pli­ca­tion for Ped­mark is still un­der EMA re­view.

There are cur­rent­ly no ap­proved drugs that pre­vent oto­tox­i­c­i­ty, or hear­ing loss, in plat­inum-based chemother­a­pies. Ped­mark, a for­mu­la­tion of sodi­um thio­sul­fate, was aim­ing for a la­bel in pe­di­atric pa­tients old­er than one month to 18 years old as the hear­ing loss stem­ming from such chemother­a­pies is of­ten long-last­ing and per­ma­nent. Typ­i­cal­ly, pa­tients who end up los­ing their hear­ing must opt for cochlear im­plants.

Ped­mark re­ceived fast track des­ig­na­tion in March 2018 fol­low­ing two Phase III stud­ies in the sur­vival and re­duc­tion of oto­tox­i­c­i­ty in five pe­di­atric can­cers that typ­i­cal­ly re­quire in­ten­sive cis­platin treat­ments.

Raykov reaf­firmed Tues­day that Ped­mark’s main func­tion is to “pre­serve hear­ing with­out re­duc­ing the ef­fec­tive­ness of cis­platin treat­ment,” and he is con­fi­dent the com­pa­ny can ap­pease the FDA in short or­der.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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With few re­main­ing un­ap­proved drugs, re­searchers tell FDA its Un­ap­proved Drugs Ini­tia­tive is no longer ef­fec­tive

Back in May, the FDA decided to reverse a Trump-era decision to pull the agency’s controversial Unapproved Drugs Initiative, with the FDA citing “multiple legal and factual inaccuracies.”

But now a group of researchers from Harvard, funded by Arnold Ventures, raises new questions about why the UDI program might not be necessary in its current form.

Designed in 2006 as a way for the FDA to transition old drugs from unapproved to approved products, the agency sought to better ensure that unsafe products were removed from the market.

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