Purepac and Ivax will split "first generic" 180-day exclusivity on their versions of Pfizer's antiepileptic Neurontin (gabapentin).

Purepac has first-to-file rights on 100 mg, 300 mg and 400 mg gabapentin capsules, while Ivax believes it will receive 180 days of exclusivity on 100 mg, 300 mg and 400 mg tablets. Purepac also expects to receive "first generic" rights on 600 mg and 800 mg tablets.

Final clearance of Purepac's generic awaits FDA approval of the manufacturing process at the company's Elizabeth, N.J. facility. The firm has completed the validation batches and is awaiting a response from FDA. Purepac does not believe it will need an inspection prior to approval.

Purepac and TorPharm had both claimed "first generic" exclusivity for gabapentin capsules on two different patents. FDA awarded the rights to Purepac after Pfizer delisted a Neurontin patent (No. 4,084,479), on which TorPharm was the first to file.

The '479 patent delisting led FDA to approve Purepac's ANDA based on the company's first-to-file rights on gabapentin patent No. 6,054,482, which claims a low-lactam version of the drug.

FDA asked Pfizer to delist the '479 patent on the basis that it covers the unapproved use of gabapentin in neurodegenerative disease. Only patents covering approved uses are eligible for listing in the "Orange Book," FDA said. Neurontin is approved for epilepsy and post-herpetic neuralgia.

The agency outlined its decision to grant Purepac 180-day exclusivity in a Jan. 28 letter to Purepac and TorPharm's parent company Apotex. FDA will award Purepac final approval in separate correspondence. TorPharm received tentative ANDA approval Jan. 29.

Once approved, Purepac will have exclusivity for the most viable doses from a marketing perspective: Pfizer sells Neurontin in 100 mg, 300 mg and 400 mg capsules; 600 mg and 800 mg tablets; and a 250 mg/5 mL oral solution. U.S. sales were $1.94 bil. in 2002.

Purepac and all other generic applicants will have to amend their ANDAs to reflect the delisting of the patent, the FDA letter says. "The withdrawal of the '479 patent from the 'Orange Book' will affect pending ANDAs for all gabapentin drug products (capsule, tablet, and solution). Applicants must amend pending ANDAs accordingly."

The exclusivity decision follows a recent Washington, D.C. federal court decision that resolved certain patent certification and exclusivity issues about gabapentin generics (¹ Also see "Generic Neurontin: Hurdles To TorPharm Approval Expected To Clear In Jan." - Pink Sheet, 6 January, 2003., p. 26).

The Dec. 16 ruling by Judge Ellen Segal Huvelle upheld Purepac's decision to file a section viii statement against the '479 patent, because it covered an unapproved use of Neurontin. TorPharm had filed a Paragraph IV certification, claiming non-infringement.

Section viii statements can be used by ANDA sponsors in lieu of a Paragraph IV certification in cases when a method of use patent does not claim the use of the drug for which the ANDA applicant is seeking approval.

Purepac filed suit against FDA in August, after the agency said the section viii statement was inappropriate and was ready to approve TorPharm's generics. FDA argued that the '479 patent did not claim a use that Purepac was "carving out" of the Neurontin indication.

The court rejected FDA's argument, however, and remanded to the agency the question of whether TorPharm still had a claim to immediate approval and/or 180-day exclusivity for its gabapentin ANDA.

FDA expressed discontent with Judge Huvelle's ruling and indicated it would have preferred to have the option of awarding shared exclusivity to Purepac and TorPharm for gabapentin capsules.

"Even though Judge Huvelle did not directly decide the question of shared exclusivity, the fundamental basis of her decision effectively decided the matter," the agency said in its letter to Purepac and TorPharm.

The court's "finding that Purepac's section viii statement was appropriate because the '479 patent does not claim a use for which Purepac - or TorPharm - was seeking approval was fatal to any claim TorPharm had to exclusivity," the letter states.

"It is possible the court could have found a different basis for permitting Purepac's section viii statement that would have given the agency more discretion in making an exclusivity decision."

"With no possibility of blocking exclusivities, as described in the November 2001 letter regarding the omeprazole ANDAs, there is no possibility that TorPharm and Purepac will have shared exclusivity for gabapentin generics," FDA explained.

In the omeprazole case, FDA split exclusivity between Andrx and GenPharm for the 10 mg and 20 mg doses; Andrx received exclusivity for 40 mg. In explaining its decision, the agency noted that both companies were first to certify against different patents for omeprazole (² Also see "Andrx Generic Prilosec Clears FDA; Approval Could Expedite Patent Litigation" - Pink Sheet, 19 November, 2001., p. 21).

The gabapentin case is similar to the omeprazole case, in that TorPharm was first to certify to the '479 patent, while Purepac had exclusivity rights to the '482 patent. Purepac and TorPharm could have shared exclusivity on gabapentin capsules if TorPharm's Paragraph IV certification were allowed to stand, which would have blocked Purepac's ANDA.

"However, given the court's specific conclusions and subsequent events, FDA believes it has little choice but to find that no applicant is eligible for 180-day exclusivity as to the patent, and to delist the '479 patent," the agency maintained.

Although Judge Huvelle did not specifically ask FDA to delist the patent, Pfizer and the agency had been communicating on the issue in the weeks prior to the court decision.

FDA received a letter from Pfizer in mid-December stating that Warner-Lambert "never represented to FDA that the '479 patent claims the approved use of gabapentin to treat epilepsy, nor was the listing intended to convey that it covers the approved use."

The agency subsequently requested that the company delist the '479 patent in a Jan. 6 letter, adding that it "reserved the right to take any action appropriate to conform the patents listed as protection for Neurontin." Pfizer notified FDA of its decision to delist Jan. 17.

With the '479 patent delisted, FDA determined that since Purepac was first to file a Paragraph IV certification against the '482 patent, it should be awarded the 180-day exclusivity period. Purepac completed its filing on June 13, 2000, three days before TorPharm completed its filing.

"Therefore, TorPharm and other ANDA applicants for gabapentin capsules must wait for final approval until the end of Purepac's exclusivity period, which will be triggered by either commercial marketing of gabapentin capsules, or by a court decision finding the '482 patent invalid or not infringed, whichever comes first," the agency's letter states.

FDA acknowledged that the "outcome in this case may seem inequitable." TorPharm "submitted a Paragraph IV certification to a listed patent as required by FDA. Moreover, it successfully defended a hard-fought patent infringement case which established important new parameters for litigation."

However, the agency adds, "there is no guarantee in the statute that, even in such compelling circumstances, an ANDA applicant will benefit from exclusivity."

"The value of exclusivity appears to be a function of timing, strategy, and luck. In TorPharm's case, exclusivity was lost to Purepac's successful defense of its section viii statement to the '479 patent."

One open question from the case is whether section viii statements and Paragraph IV certifications are mutually exclusive. While FDA's regulations state that an applicant cannot file both on the same patent, it remains unclear if different applicants can file different sections.

From Pfizer's point of view, Purepac's victory over TorPharm may play in its favor. While TorPharm had publicly declared its intent to bring its generic to market should it be cleared by FDA, Purepac is still determining when it will launch, once approved.

Purepac and TorPharm remain in litigation with Pfizer over the '482 patent, although TorPharm said it would launch its generic regardless of the status of the litigation. A trial is expected in the second half of 2003, should the court deny Purepac's request for summary judgment.

Purepac has three options on launch timing: launch immediately, and risk paying treble damages to Pfizer if it loses the '482 patent lawsuit; wait for a decision of summary judgment; or wait for a final court decision.

Pfizer says it holds another patent on Neurontin for use in post-herpetic neuralgia, which could further complicate the launch timing. Pfizer also maintains that generic companies will have difficulty obtaining sufficient bulk supplies to make significant inroads in the U.S. (³ Also see "Neurontin Bulk Supply May Limit Generic Uptake, Pfizer Says" - Pink Sheet, 27 January, 2003., p. 18).

Purepac Gabapentin Is “First Generic” After Pfizer Delists Neurontin Patent

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