Court sides with FDA in Van­da clin­i­cal hold suit

The US Dis­trict Court for the Dis­trict of Co­lum­bia on Fri­day ruled in the FDA’s fa­vor in a case brought by Van­da Phar­ma­ceu­ti­cals con­cern­ing a par­tial clin­i­cal hold placed on a study of the com­pa­ny’s in­ves­ti­ga­tion­al drug tradip­i­tant in De­cem­ber 2018.

In the de­ci­sion, Judge John Bates de­nied Van­da’s mo­tions for sum­ma­ry judge­ment and re­fused to al­low the fil­ing of an am­i­cus brief by the Hu­mane So­ci­ety that chal­lenged the FDA’s jus­ti­fi­ca­tion for an ad­di­tion­al an­i­mal study.

In a state­ment Fri­day, Van­da said it is re­view­ing the de­ci­sion and “will de­ter­mine the ap­pro­pri­ate next steps.”

Back­ground

The dis­pute cen­ters on the FDA’s de­ci­sion to place a hold on a 52-week open-la­bel ex­ten­sion to a Phase II study of tradip­i­tant to treat gas­tro­pare­sis un­til Van­da con­duct­ed a nine-month non­ro­dent tox­i­c­i­ty study to sup­port the use of the drug in hu­mans be­yond 12 weeks.

In April 2018, Van­da first sought a 52-week ex­ten­sion to its ini­tial four week Phase II study but re­duced the ex­ten­sion to eight weeks af­ter the FDA said it did not have enough safe­ty da­ta to sup­port tradip­i­tant’s use in hu­mans be­yond three months.

Van­da sought to ex­tend the study by 52 weeks twice more in 2018 be­fore the FDA placed a par­tial clin­i­cal hold on the tri­al, in­sist­ing that nine-month non­ro­dent tox­i­c­i­ty stud­ies “are re­quired … per the [In­ter­na­tion­al Coun­cil for Har­mon­i­sa­tion] ICH Guid­ance for In­dus­try : M3(R2) Non­clin­i­cal Safe­ty Stud­ies for the Con­duc­tion of Hu­man Clin­i­cal Tri­als and Mar­ket­ing Au­tho­riza­tion for Phar­ma­ceu­ti­cals.”

On 5 Feb­ru­ary 2019, Van­da sued the FDA over the par­tial clin­i­cal hold, al­leg­ing that the FDA failed “to ar­tic­u­late an ad­e­quate sci­en­tif­ic ba­sis” for the hold and in­sist­ing that the rec­om­men­da­tions in the ICH guid­ance are non-bind­ing. In re­sponse to the suit, FDA asked the court for a vol­un­tary re­mand to “ad­dress cer­tain pro­ce­dur­al is­sues” in the com­plaint.

Af­ter re­view­ing Van­da’s pro­pos­als, the FDA is­sued a re­sponse con­clud­ing that “ex­ist­ing tradip­i­tant stud­ies in non­ro­dents con­tain suf­fi­cient trou­bling in­di­ca­tions of tox­i­c­i­ty such that—while short­er-term hu­man stud­ies may be safe enough to pro­ceed—FDA needs to see if those tox­i­c­i­ty mark­ers in­crease dur­ing long-term non­ro­dent stud­ies be­fore al­low­ing long-term hu­man stud­ies,” and pro­vid­ing a sci­en­tif­ic ra­tio­nale for its re­quest for a nine-month non­ro­dent study.

Anal­y­sis

In the de­ci­sion, Bates re­ject­ed Van­da’s ar­gu­ment that the jus­ti­fi­ca­tion for the clin­i­cal hold made in the FDA’s re­mand re­sponse is “im­per­mis­si­ble post hoc ra­tio­nal­iza­tion,” find­ing that the re­mand re­sponse was made by prop­er de­ci­sion­mak­ers at the FDA and that the re­sponse ap­pro­pri­ate­ly ex­pand­ed on the agency’s ear­li­er de­ci­sion.

The judge al­so re­ject­ed Van­da’s as­ser­tion that the FDA “se­lec­tive­ly opened the record up­on re­mand, adding new stud­ies that sup­port its po­si­tion but fail­ing to add stud­ies ref­er­enced in Van­da’s com­plaint or in a let­ter mailed by the Hu­mane So­ci­ety.” Ac­cord­ing to the rul­ing, “the re­mand mo­tion did not re­quire FDA to con­sid­er ad­di­tion­al ev­i­dence from Van­da; (2) no le­gal au­thor­i­ty re­quired FDA to con­sid­er ad­di­tion­al ev­i­dence form Van­da or the Hu­mane So­ci­ety; and (3) Van­da de­lib­er­ate­ly de­clined to take ad­van­tage of the ad­min­is­tra­tive means avail­able for in­tro­duc­ing its de­sired ev­i­dence in­to the record.”

Van­da’s claim that the FDA ap­plied the ICH guid­ance as a bind­ing leg­isla­tive rule is al­so tossed out. “Though some of FDA’s com­ments pre-re­mand sug­gest­ed that the ICH Guid­ance im­posed a ‘re­quire­ment’ on Van­da, even the ini­tial clin­i­cal hold let­ter did not re­ly on the ICH Guid­ance as the le­gal source of au­thor­i­ty—in­stead, it cit­ed the con­trol­ling reg­u­la­tion as the ba­sis for the hold,” the judge wrote, not­ing that the ICH guid­ance “is a gen­er­al pol­i­cy state­ment” and not a leg­isla­tive rule re­quir­ing a no­tice-and-com­ment rule­mak­ing process.

Ad­di­tion­al­ly, the judge re­ject­ed Van­da’s as­ser­tion that the FDA failed to demon­strate that ca­nine stud­ies are pre­dic­tive of ef­fects in hu­mans.

“Van­da’s ar­gu­ment is un­per­sua­sive for the ba­sic rea­son that the statu­to­ry and reg­u­la­to­ry scheme here ex­plic­it­ly con­tem­plates that the re­sults of an­i­mal stud­ies are pre­dic­tive of the re­sults of hu­man tri­als,” the judge wrote.


RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Lat­est on ul­tra-rare dis­ease ap­proval; Pos­i­tive, if mixed, signs for Bio­gen's ALS drug; Clay Sie­gall finds a new job; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Over the last four years, we’ve honored 80 women whose extraordinary accomplishments have changed the game in biopharma R&D. You can now nominate someone to be highlighted in this year’s special report. Details are here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

FDA spells out how can­cer drug de­vel­op­ers can use one tri­al for both ac­cel­er­at­ed and full ap­provals

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Sijmen de Vries, Pharming CEO

FDA ap­proves Pharm­ing drug for ul­tra-rare im­mun­od­e­fi­cien­cy dis­ease

US regulators cleared an ultra-rare drug from Pharming Group, by way of Novartis, on Friday afternoon.

The Dutch biotech said the FDA greenlit leniolisib for an immunodeficiency disease known as activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome, or APDS. People 12 years and older can receive the oral drug, to be marketed as Joenja, beginning early next month, Pharming said, five days ahead of the decision deadline set by the FDA as part of a priority review.

No­vo Nordisk oral semaglu­tide tri­al shows re­duc­tion in blood sug­ar, plus weight loss

Novo Nordisk is testing higher levels of its oral version of its GLP-1, semaglutide, and its type 2 diabetes trial results released today show reductions in blood sugar as well as weight loss.

In the Phase IIIb trial, Novo compared its oral semaglutide in 25 mg and 50 mg doses with the 14 mg version that’s currently the maximum approved dose. The trial looked at how the doses compared when added to a stable dose of one to three oral antidiabetic medicines in people with type 2 diabetes who were in need of an intensified treatment.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Ly­me vac­cine test com­ple­tion is pushed back by a year as Pfiz­er, Val­ne­va say they'll ad­just tri­al

Valneva and Pfizer have adjusted the end date for the Phase III study of their investigational Lyme disease vaccine, pushing it back by a year after issues at a contract researcher led to thousands of US patients being dropped from the test.

In a March 20 update to clinicaltrials.gov, Valneva and Pfizer moved the primary completion date on the trial, called VALOR, from the end of 2024 to the end of 2025.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Stuart Peltz, former PTC Therapeutics CEO

Stu­art Peltz re­signs as PTC Ther­a­peu­tics CEO af­ter 25 years

Stuart Peltz, the longtime CEO of PTC Therapeutics who’s led the rare disease drug developer since its founding 25 years ago, is stepping down.

Succeeding him in the top job is Matthew Klein, who joined PTC in 2019 and was promoted to chief operating officer in 2022. In a call with analysts, he said the CEO transition has been planned for “quite some time” — in fact, as part of it, he gave the company’s presentation at the JP Morgan healthcare conference earlier this year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.