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.

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