Catalyst Alleges US FDA 'Facilitating' Off-Label Use With Jacobus' Ruzurgi Approval
Executive Summary
Lawsuit seeking invalidation of rare disease treatment's approval in Lambert-Eaton myasthenic syndrome encompasses policy trifecta of exclusivity, drug pricing, and expanded access issues.
A lawsuit alleges that a US Food and Drug Administration tentative approval letter actually encouraged off-label use of a rare disease treatment, creating competition for a product that had obtained temporary monopoly power.
Catalyst Pharmaceuticals Inc. sued the FDA on 12 June demanding that the approval of Jacobus Pharmaceutical Co.'s Ruzurgi (amifampridine) should be invalidated because it violates the orphan and new chemical entity exclusivity awarded to Catalyst's Firdapse (amifampridine).
Firdapse was approved in 2018 as a treatment for adults with Lambert-Eaton myasthenic syndrome (LEMS), while Ruzurgi was approved in 2019 for pediatric use in the same disease.
Catalyst said in a court filing that when the FDA approved Ruzurgi for pediatric use on 6 May and issued a same-day tentative approval letter saying the product couldn't be approved in adults because it was blocked by Firdapse's orphan exclusivity, the agency was in effect sanctioning off-label use in the adult population.
Catalyst said it was not aware of any precedent "for issuing such letters in the specific context," and the FDA was "effectively using Catalyst's [orphan drug exclusivity] to facilitate off-label sales" of Ruzurgi.
"FDA has essentially told the public that the agency would have approved Ruzurgi as safe and effective in adults but for Catalyst’s exclusivity – again in effect signaling that Ruzurgi can be used in the patient population for which Catalyst has exclusivity," Catalyst said in the suit, which requests that Ruzurgi's approval be declared unlawful and vacated and the agency barred from approving other applications that violate the Firdapse exclusivity.
Jacobus is not named in the complaint, and the company did not respond to a request for comment.
Catalyst also said Ruzurgi's labeling also suggests adult use is permissible because it indicates that safety and efficacy in children age 6 to 17 was determined because of its safety and efficacy in adults. The lone study used for approval included patients age 23 to 83, according to the court filing.
Ruzurgi's label states that safety also was evaluated in 15 pediatric LEMS and non-LEMS patients age 6 to less than 17 that were treated in expanded access programs.
Expanded access data has been used previously to support approvals, including in rare diseases. (Also see "Baby Steps To Real-World Evidence Of Efficacy: External Controls Gain Popularity In Rare Disease Trials" - Pink Sheet, 16 Apr, 2019.)
The FDA sometimes finds difficulty labeling drugs with indications that are protected by exclusivity. When the agency approved Celltrion Inc.'s Inflectra (infliximab-dyyb), a biosimilar of Janssen Biotech Inc.'s Remicade (infliximab), language in the label suggested the product was safe for use in a Remicade indication protected by orphan exclusivity, seemingly inviting off-label use.
Rare disease advocates complained that discussion of the indication during the advisory committee meeting on Inflectra was problematic. (Also see "Inflectra Label Not Exactly Silent On Remicade's Orphan-Protected Claim" - Pink Sheet, 5 Apr, 2016.)
Catalyst: Orphan Exclusivity Must Be Protected
Catalyst Chairman and CEO Patrick McEnany said in a written statement announcing the suit that the FDA "misapplied its regulations" and undercut the company's orphan drug exclusivity.
"We are compelled to bring this action, to preserve the specialized regulatory framework provided by the orphan drug legislation, and the prospect of future rare disease drug development for all rare disease patients in need of an approved treatment," the company said.
Indeed, a lawsuit regarding Ruzurgi likely was not surprising given the unusual circumstances surrounding the approval. Firdapse and Ruzurgi both received orphan drug designations, and the agency decided to split the Ruzurgi application into separate adult and pediatric NDAs.
Interestingly, at the time of Ruzurgi's approval, Catalyst described it as the same chemical entity as Firdapse, but formulated differently. While Ruzurgi is a free base amifampridine, Firdapse includes a phosphate salt that the company said offers more assurance of the correct purity and potency and does not need constant refrigeration. (Also see "Keeping Track: US FDA Approves Pfizer’s Vyndaqel, Jacobus’ Ruzurgi, But Nixes Acacia’s Barhemsys Again" - Pink Sheet, 12 May, 2019.)
The FDA approved Firdapse on 28 November 2018. (Also see "Keeping Track: US FDA Enters Year's Final Stretch With Tsunami Of Novel Approvals " - Pink Sheet, 1 Dec, 2018.)
Drug Pricing Debate Suggested As Factor In Ruzurgi Approval
The case also touches the politics of health care, namely the debate over drug pricing.
Catalyst said in the suit that the FDA approved Ruzurgi "based upon a misperception regarding the pricing of Firdapse," even though the agency cannot consider price when making approval decisions. The company said the agency knew Jacobus could not recoup its development costs selling the drug only to pediatric LEMS patients – Catalyst cited Jacobus data in the filing that there were less than 15 known in the US – "without also illegally marketing off-label to adult patients."
After Firdapse was approved, complaints emerged about its $375,000 per year price. Sen. Bernie Sanders, I-VT, said in a letter that the price was blatant fleecing of American taxpayers.
Catalyst said in the suit that most patients pay $10 or less per month through a company patient insurance navigation and financial assistance program. Patients with no insurance receive it at no cost.
Catalyst also argued that Ruzurgi's expected annual price of $175,200, based on an average dose of 60mg, provides an economic incentive for adult patients to switch to Ruzurgi, a product not approved for them.
The argument that drug pricing played into the FDA's decision-making regarding Firdapse and Ruzurgi is interesting because of the agency's more active approach to the issue.
Former Commissioner Scott Gottlieb said multiple times that the agency could help lower drug costs for patients, even though it could not take pricing into account when making approval decisions. (Also see "Gottlieb Places Drug Pricing Out Front In First Speech To US FDA Staff" - Pink Sheet, 16 May, 2017.)
Gottlieb called for increasing competition through approval of more generics, as well as novel products in areas where there were only a few treatments. (Also see "Q&A With US FDA Commissioner Scott Gottlieb" - Pink Sheet, 9 Nov, 2017.)
FDA Treated Jacobus Differently, Catalyst Says
Catalyst also said in the suit that the FDA treated Jacobus differently in the requirements made pre- and post-approval of Ruzurgi.
The company said Jacobus was allowed to submit a juvenile animal toxicology study and a clinical trial evaluating Ruzurgi's effect on kidneys postmarketing, while Catalyst was required to submit an animal toxicology study and clinical trial evaluating Firdapse on kidneys before its product was assessed.
"FDA also accelerated the time for Jacobus to submit its NDA by not requiring the same testing data it required before even reviewing Plaintiff’s NDA – much less approving it," Catalyst said in the court filing.
Catalyst also argued that the FDA should not have allowed Ruzurgi to be approved through the conventional new drug application pathway and instead forced the product to use the 505(b)2 path. The company said "Jacobus' application relied, directly or by implication, upon studies conducted and data collected and submitted by Catalyst for the Firdapse approval without a right of reference."
"In essence, because FDA concluded that Firdapse was safe and effective, it knew Ruzurgi was as well," Catalyst said in the filing. "But had Ruzurgi been adjudicated under the correct pathway, it would be blocked by Firdapse’s NCE [exclusivity]."
The case was filed in the US District Court for the Southern District of Florida.