De­cry­ing 'ar­bi­trary and capri­cious' ac­tion, Re­genxBio sues FDA over clin­i­cal holds on gene ther­a­py

When Re­genxBio dis­closed that the FDA had placed a par­tial clin­i­cal hold on one of its lead gene ther­a­pies, ex­ecs out­lined sev­er­al cus­tom­ary next steps: con­tin­u­ing as­sess­ment and mon­i­tor­ing, de­lay­ing a re­lat­ed IND fil­ing, and work­ing with the FDA to ad­dress the mat­ter.

As it turned out, they were plan­ning some­thing much less mun­dane. Two days af­ter an­nounc­ing the hold in its Q3 up­date, Re­genxBio filed a law­suit seek­ing to set it aside, the FDA Law Blog not­ed.

The law­suit shed light on the in­ter­ac­tions be­tween the biotech and reg­u­la­tors, re­veal­ing that there was ac­tu­al­ly a full clin­i­cal hold on the di­a­bet­ic retinopa­thy tri­al in ad­di­tion to the par­tial hold on wet age-re­lat­ed mac­u­lar de­gen­er­a­tion and Re­genxBio with­drew the IND.

Ac­cord­ing to the com­plaint, the com­pa­ny had dis­cussed re­sults from its Phase I/IIa tri­al with the FDA and was on track to be­gin the next phase be­fore the end of 2019.

But on Oc­to­ber 18, 2019, with­out no­tice or ex­pla­na­tion, FDA placed RGX-314 on a clin­i­cal hold, ef­fec­tive­ly halt­ing RE­GENXBIO’s de­vel­op­ment of this po­ten­tial­ly life-al­ter­ing treat­ment for reti­nal dis­eases that are lead­ing caus­es of adult blind­ness. Since is­su­ing the clin­i­cal hold or­der, FDA has re­buffed RE­GENXBIO’s re­peat­ed at­tempts to ob­tain an ex­pla­na­tion of the ba­sis for the clin­i­cal hold.

Fail­ing to pro­vide ad­vance warn­ing or ex­pla­na­tion for the hold, Re­genxBio claims, is in vi­o­la­tion of the FDA’s own reg­u­la­tions. And that led to an “ar­bi­trary and capri­cious” fi­nal de­ci­sion, they wrote.

But that’s not it.

Since they didn’t get a chance to re­view or re­but the rea­sons for the hold, which harmed their rep­u­ta­tion and prop­er­ty in­ter­est in RGX-314, Re­genxBio be­lieves the FDA vi­o­lat­ed the Fifth Amend­ment’s Due Process Clause. Fur­ther­more, they charged a par­tic­u­lar sec­tion of the Food, Drug, and Cos­met­ic Act rep­re­sent­ed an un­con­sti­tu­tion­al vest­ing of leg­isla­tive pow­er in the Sec­re­tary of Health and Hu­man Ser­vices.

Along with the agency, the fed­er­al gov­ern­ment, HHS Sec­re­tary Alex Azar, act­ing FDA com­mis­sion­er Brett Giroir (who has tak­en over from Ned Sharp­less while Stephen Hahn goes through the con­fir­ma­tion process), and FDA reg­u­la­to­ry project man­ag­er Ed­ward Thomp­son were al­so named as de­fen­dants. Thomp­son al­leged­ly first no­ti­fied Re­genxBio of the holds cit­ing “is­sues as­so­ci­at­ed with [RGX-314’s] de­liv­ery sys­tems.”

Fol­low­ing mul­ti­ple ex­changes, the FDA ap­par­ent­ly told Re­genxBio that it would pro­vide a writ­ten ex­pla­na­tion of the ba­sis for the hold by this Fri­day, No­vem­ber 15.

Why risk the ire of reg­u­la­tors when an up­date is due so soon? As a pro­ce­dur­al mat­ter to pre­serve their rights, the com­pa­ny said.

“This ac­tion was tak­en on the rec­om­men­da­tion from coun­sel as we con­tin­ue to work with the FDA to ad­dress this mat­ter, and we hope this step will help en­sure the FDA will pro­vide Re­genxBio with their spe­cif­ic con­cerns about the un­spec­i­fied de­vice,” it wrote in an email to End­points News.

At­tor­ney Deb­o­rah Livor­nese of­fered this take on the FDA Law Blog:

While it seems un­like­ly that the mer­its of the clin­i­cal hold will be re­solved through the ju­di­cia­ry process in a help­ful time­frame, the com­plaint has like­ly in­creased the chances that FDA will re­spond with a thor­ough ex­pla­na­tion of its rea­son for the hold when it does pro­vide the writ­ten ba­sis.

The biotech added that the plan is still to start the wet AMD tri­al and file an IND for di­a­bet­ic retinopa­thy in Q2 2020, “as we be­lieve that there are read­i­ly avail­able and suit­able al­ter­na­tives for all of the de­vices used in our stud­ies.”

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Thomas Gad, Y-mAbs Therapeutics founder and interim CEO

FDA re­jects Y-mAbs’ neu­rob­las­toma drug af­ter tak­ing is­sue with clin­i­cal tri­al de­sign

Uncertainty about clinical trial evidence has led the FDA to hand down a complete response letter for Y-mAbs’ neuroblastoma drug, casting a cloud on the future of a candidate that had gone through a long development journey in a rare pediatric cancer.

Y-mAbs said it’s disappointed “but not surprised” given that the agency’s oncology drug advisory committee had voted 16-0 against its drug’s approval a few weeks ago.

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Raul Rodriguez, Rigel Pharma CEO

Rigel Phar­ma scores FDA ap­proval for leukemia, kick­ing off show­down with Servi­er in IDH1

When Rigel Pharma bought olutasidenib from Forma Therapeutics, it acquired a drug that already secured a PDUFA date at the FDA — for February 2023. But regulators are ready to give their OK sooner than that.

The FDA has approved the IDH1 inhibitor as a treatment for adult patients with relapsed or refractory acute myeloid leukemia who have a susceptible IDH-1 (isocitrate dehydrogenase-1) mutation as detected by an FDA-greenlit test. Rigel will market it as Rezlidhia.

Philip Tagari switch­es Am­gen's dis­cov­ery lab for in­sitro's ma­chine learn­ing tools; CEO Joaquin Du­a­to to chair J&J's board

In February, Philip Tagari will take a few days of retirement and then immediately return to industry. He won’t be leading the therapeutics discovery unit for a large biopharma, though.

He’ll trade in his Amgen hat for chief scientist at a machine learning startup that has reeled in hundreds of millions in capital to lay the groundwork for a much-hyped new model of drug discovery that aims to speed up the time to new clinical assets.

Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and Am­gen are bring­ing cash to cov­er the ta­ble stakes for the Hori­zon M&A game

With the market cap on Horizon Therapeutics $HZNP pushed up to the $23 billion mark today, one of the Big Pharmas in the hunt for a major league buyout deal signaled it’s playing the M&A game with cash.

Paris-based Sanofi, where CEO Paul Hudson has been largely focused on some risky biotech acquisitions to win some respect for its future pipeline prospects, issued a statement early Friday — complying with Rule 2.12 of the Irish takeover rules — making clear that while the certainty or size of an offer can’t be determined, any offer “will be solely in cash.” And Amgen CEO Robert Bradway came right in behind him, filing a statement on the London Stock Exchange overnight that any offer they may make will “likely” be in cash as well.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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Tim Pearson, Carrick Therapeutics CEO

Pfiz­er backs $60M in­fu­sion in­to Car­rick, teams up on breast can­cer treat­ment

In a big week for Carrick Therapeutics, the company announced $60 million in funding for its lead breast cancer drug and development of a second program, as well as a collaboration with Pfizer for combo development.

The $35 million from Pfizer comes with an agreement under which Pfizer will support Carrick’s Phase II study of samuraciclib in combination with Pfizer’s Faslodex for advanced breast cancer. Along with the investment, Adam Schayowitz, vice president and development head of breast cancer, colorectal cancer and melanoma at Pfizer global product development, will join Carrick’s scientific advisory board.

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Tim Van Hauwermeiren, argenx CEO

Ar­genx pur­chas­es $100M+ FDA pri­or­i­ty re­view vouch­er from blue­bird bio

Argenx’s Vyvgart is due for a speedy review at the FDA, thanks to a $102 million priority review voucher (PRV).

The Netherland-based biotech picked up the PRV from bluebird bio, the companies announced on Wednesday. PRVs shorten a drug’s FDA review period from 10 months to 6 months, though they often sell on the open market for around $100 million each.

Argenx plans on using the express ticket on efgartigimod, its neonatal Fc receptor (FcRn) blocker marketed as Vyvgart for adults with generalized myasthenia gravis (gMG). While Vyvgart won its first approval last December for the chronic neuromuscular disease — which is characterized by difficulties with facial expression, speech, swallowing and breathing — CEO Tim Van Hauwermeiren said in a news release that he plans to “be active in fifteen disease targets by 2025.”