In a very interesting decision, the United States District Court for the District of Columbia ruled that the FDA erred in not granting a pediatric rare disease voucher to Sun Pharmaceutical’s injectable phenobarbital drug for the treatment of a rare seizure disorder in pediatric patients less than four years of age.

The Court cited statutory elements of qualification for a rare pediatric voucher as follows:

    1. The application must be a new drug application (NDA) made under Section 505(b)(1) of the FDCA.
    2. The drug must be intended “for the prevention or treatment of a rare pediatric disease.”
    3. The NDA must be “deem[ed] eligible for priority review.”
    4. The NDA must rely on clinical data from a study evaluating a pediatric population and dosages for that population.
    5. The NDA must not seek approval for an adult indication.
    6. The NDA must be approved after September 30, 2016, and before September 30, 2026 (when the Act was set to sunset).
    7. The NDA must seek approval for “a drug . . . that contains no active moiety . . . that has been previously approved in any other application under subsection (b)(1), (b)(2), or (j) of section 355 of this title.”

 

It is the seventh provision of the requirements cited above that the judge found that the FDA had erred in applying in denying the award of the pediatric voucher.

On November 17, 2022, “Sun Pharma Advanced Research Company, Ltd. And Sun Pharmaceutical Industries, Inc. received approval from the FDA for their drug Sezaby to treat neonatal seizures” and in that letter the FDA also denied the firm’s request for a Pediatric Rare Disease Voucher.

In a separate letter, the FDA described its rationale for denying granting the pediatric voucher saying that “[a]lthough the FDA had not ‘identif[ied] any applications for phenobarbital containing drugs that were approved after the Hatch-Waxman amendments were passed in 1984,’ it had ‘identified at least one NDA for a drug product containing phenobarbital as an active moiety that came into effect before 1962 and was deemed approved by the 1962 Amendments: NDA 000597 for Phenobarbital and Atropine.’” “The agency explained that this prior ‘deemed’ approval of NDA 000597 blocked Plaintiffs’ receipt of a priority review voucher.”

The Court went on to explain the history of NDA 000597, which “was submitted in 1939 for a tablet containing a combination of phenobarbital and atropine for limited distribution only to licensed physicians.” It was “deemed” approved three weeks after its submission. The 1962 Amendments to the FDCA required “‘affirmative agency approval’ based on ‘substantial evidence’ that the drug is effective.” However, under that new statutory regime, it “permitted a drug ‘deemed’ approved to remain on the market after 1962, but the FDA after two years could order its removal, unless it was shown to be effective under the new regime.” “NDA 000597 would not survive the greater scrutiny imposed by the 1962 Amendments. In 1972, the FDA determined that there was a lack of substantial evidence to support the effectiveness of the drug,” “and in 1977, the agency proposed to withdraw NDA 000597 because its sponsor failed to provide studies showing the drug’s effectiveness.” The decision notes that “[t]he drug’s sponsor discontinued distribution weeks later and, in 1978, ‘request[ed] the withdrawal’ of the application and ‘waive[d] the right to a hearing.’” “[I]n 1982, the FDA formally withdrew ‘approval’ of NDA 000597.”

In the judge’s decision, he noted “Congress ‘deemed’ ‘approved’ NDAs like NDA 000597, which had become effective by agency inaction, did not make those drugs ‘approved’ in the same sense as one receiving affirmative FDA approval, as the 1962 Amendments required going forward. Nowhere did Congress indicate that it meant to make them equivalent for all purposes. To the contrary, Congress in 1962 intended for ‘deemed’ approval status to function only temporarily, until the drug sponsor submitted substantial evidence backing the drug’s effectiveness.”

The conclusion was, therefore, that phenobarbital had never been “approved” by the FDA in any NDA for any product and especially in the light of the new statutory scheme enacted by the Hatch-Waxman Amendments of 1984 and including those provisions later codified for Pediatric Rare Disease Vouchers. The decision is extremely interesting, and it will be even more interesting if the FDA decides to appeal the decision. This blog very briefly summarizes the judge’s decision; it would behoove you to read the full decision (here) as it clearly could be a once-in-a-lifetime regulatory event, so to speak.

We all know the vouchers that the FDA issues for Pediatric Rare Diseases (along with other types of vouchers issued for certain therapies) are extremely valuable. They provide for an expedited six-month NDA review when used, and they can be sold for use by another company. Many sell for tens of millions of dollars, with one having been sold by United Therapeutics for $350 million. While Sun could not now benefit from a six-month review, it certainly could from the sale of the voucher!

Just when you think you’ve seen it all, a new twist or turn emerges in the ever-changing interpretation of statutory or regulatory provisions!