Court Sides With FDA in Vanda Clinical Hold Suit
Regulatory News | 03 February 2020 |
The US District Court for the District of Columbia on Friday ruled in the US Food and Drug Administration’s (FDA) 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 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 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 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 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 FDA over the partial clinical hold, alleging that 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, 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 FDA’s remand response is “impermissible post hoc rationalization,” finding that the remand response was made by proper decisionmakers at FDA and that the response appropriately expanded on the agency’s earlier decision.
The judge also rejected Vanda’s assertion that 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 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 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.
Ruling
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 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 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 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 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 FDA over the partial clinical hold, alleging that 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, 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 FDA’s remand response is “impermissible post hoc rationalization,” finding that the remand response was made by proper decisionmakers at FDA and that the response appropriately expanded on the agency’s earlier decision.
The judge also rejected Vanda’s assertion that 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 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 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.
Ruling
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