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.”

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Can a mag­net­ic cell ther­a­py re­place corneal trans­plan­ta­tion? As eight-year jour­ney leads to the clin­ic, two broth­ers un­veil bold vi­sion

Jeff Goldberg was getting acquainted with a brand new way to do corneal transplants when an even newer, even bolder idea hit him.

It was almost 10 years ago, and Goldberg was in his first faculty position at Bascom Palmer Eye Institute at the University of Miami. Scientists had developed a new way to do cornea transplants where instead of sewing a whole donor cornea — a decades-old practice — they were just engrafting the inner layer of cells.

Blueprint CEO Jeff Albers (file photo)

Blue­print plots re­turn to FDA with new Ay­vak­it da­ta in rare con­di­tion — and the an­a­lysts cheer

Over a decade after launch, Blueprint Medicines nabbed the first approval for their first drug earlier this year. Now, as they move forward with a Roche-partnered global launch, they’re touting data that could push them into more patients.

The Jeff Albers-led Cambridge biotech released their full pivotal data for Ayvakit in patients with advanced systemic mastocytosis. In one 53-person study, they showed that 76% of patients responded to the drug, 36% had complete responses and that on average their responses lasted for just over 3 years. A smaller, 32-patient study had a 75% response rate and most were still responding after 10.4 months, the last follow-up.

News brief­ing: Tiny Vac­cinex's drug flops in PhII Hunt­ing­ton's tri­al, stock craters; Siol­ta nabs $30M Se­ries B to de­vel­op mi­cro­bio­me drug

Siolta Therapeutics, a microbiome company targeting allergic diseases, raked in a $30 million Series B to develop its lead candidate, STMC-103H. The drug, which has been FDA fast-tracked, is headed for proof-of-concept trials, according to the company. Its various indications include allergic asthma, food allergies, atopic dermatitis, allergic rhinitis, and allergy prevention.

The news comes just after the California-based biotech added a prominent biopharma veteran as an advisor: 20-year Gilead CEO John Martin. The biotech also gained Richard Shames as CMO, who came by way of Protagonist Therapeutics.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Frank Zhang (AP Images)

UP­DAT­ED: Rocked by cus­toms in­ves­ti­ga­tion, Leg­end's CFO takes over as CEO Frank Zhang placed un­der house ar­rest

When Frank Zhang stepped down from GenScript — the contract research group he’s run for 18 years — to take up the CEO post at its CAR-T focused spinout Legend Biotech, he assured analysts that he was in for the long haul.

Just 49 days later, though, he’s been forced to hand back the title.

In a dramatic turn of events, Legend disclosed that Zhang is under house arrest in China as part of a customs investigation involving GenScript. While he remains the chairman, CFO Ying Huang has been tapped to double as interim CEO.

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