Ranbaxy Exclusivity Implosion Pushes Valcyte Generics Towards Launch; Nexium Remains ‘Very Hazy’
This article was originally published in The Pink Sheet Daily
Executive Summary
FDA rescinds Ranbaxy’s esomeprazole and valganciclovir ANDA tentative approvals because of GMP compliance issues; firm loses its 180-day marketing exclusivity for valganciclovir but not for esomeprazole.
Generic firms may soon launch generic versions of Roche’s antiviral Valcyte (valganciclovir) but it remains unclear whether Ranbaxy Laboratories Ltd.’s tie up of the generic market for AstraZeneca PLC’s heartburn drug Nexium (esomeprazole) will continue.
Ranbaxy announced in a Nov. 6 statement to the Indian Stock Exchange that FDA had rescinded the tentative approvals it had granted for Ranbaxy’s ANDAs for esomeprazole and valganciclovir. “FDA has said that its original decisions granting tentative approvals were in error because of the compliance status of the facilities referenced in the ANDAs at the time the tentative approvals were granted.”
“As a consequence, in FDA’s view, Ranbaxy has forfeited its eligibility for 180-day exclusivity for valganciclovir hydrochloride tablets,” Ranbaxy said.
The company posted a similar statement on its website, adding that FDA determine the ANDAs “did not have any data integrity issues.” Ranbaxy did not say anything about its exclusivity for esomeprazole.
The company did not say anything about its exclusivity for esomeprazole and did not respond to queries seeking clarification on its status.
Ranbaxy was the first to file ANDAs for both products. Their final approval has been delayed because of manufacturing problems at the company’s Indian facilities. The company signed a consent decree earlier in the year and FDA imposed an import alert on its Toansa site, effectively banning it from exporting products to the U.S., after finding current good manufacturing practice violations (Also see "U.S. FDA Now Bans Ranbaxy’s Toansa API Facility; Company Apologizes To Stakeholders" - Pink Sheet, 24 Jan, 2014.).
Ranbaxy’s announcement caused a stir in industry as esomeprazole ANDA holders tried to figure out what it meant for them. A spokesperson for Dr. Reddy's Laboratories Ltd. said the situation is “very hazy” and that it appears that Ranbaxy is trying to hold onto generic Nexium market exclusivity.
One possibility is that Ranbaxy has been able to transfer its esomeprazole application to its New Jersey plant, as it successfully did when it hung onto generic exclusivity for Pfizer Inc.’s Lipitor (atorvastatin), but the review of the modified esomeprazole ANDA is not complete so the tentative approval was rescinded.
While the fate of generic Nexium is uncertain, FDA said it has granted tentative approval to Dr. Reddy’s and Endo Pharmaceuticals Inc. ANDAs for valganciclovir. The Dr. Reddy’s spokesperson said the company has started the process to launch in the U.S. as soon as possible following final FDA approval, which is expected shortly now that Ranbaxy has forfeited exclusivity.
Ranbaxy Exclusivity Question is ‘Complex,’ FDA Says
Nexium is AstraZeneca’s third top-selling drug, generating revenue of $922 million in the third quarter of 2014. Ranbaxy’s inability to launch has been a boon to AstraZeneca, which has been able to hold onto the market for five months longer than it expected. Ranbaxy had the right to launch its product on May 27 under the terms of a 2008 settlement agreement with AstraZeneca (Also see "AstraZeneca Settles Nexium Case With Ranbaxy; Can It Delay Other Generics?" - Pink Sheet, 21 Apr, 2008.).
Other ANDA filers also reached agreements with AstraZeneca to launch their products in May, five years before the latest Nexium patent expires (Also see "Nexium Patent Battle Could Switch To Generic Vs. Generic Fight" - Pink Sheet, 7 Jan, 2010.).
It is uncertain why FDA decided Ranbaxy had forfeited its exclusivity for valganciclovir but not for esomeprazole. Kurt Karst, of Hyman, Phelps & McNamara, said in an FDA Law Blog post that FDA’s action on Ranbaxy’s Valcyte generic “necessarily raises the question as to whether or not the agency is poised to take a similar action with respect to Ranbaxy’s ANDA for generic Nexium.”
Karst noted that FDA recently removed any mention of Ranbaxy’s tentative ANDA approval for generic Nexium from its Drugs@FDA website, just as it did with generic Valcyte.
Karst’s firm filed a citizen petition in May on behalf of an unnamed client seeking to nullify Ranbaxy’s award of 180-day exclusivity for a generic version of Novartis AG’s hypertension drug Diovan (valsartan), which went off patent in September 2012. The petition contended that Ranbaxy was ineligible for first-to-file exclusivity because its application was incomplete due to data integrity violations” (Also see "Teva Claims Diovan 180-Day Exclusivity, Arguing Ranbaxy ANDA Was Incomplete" - Pink Sheet, 12 Jun, 2014.).
The petition also noted that esomeprazole and valganciclovir generics were stuck in a similar regulatory quagmire because of Ranbaxy’s first applicant status.
Ranbaxy finally won approval for its generic valsartan in June, which suggests FDA decided to deny the petition even though it has not definitively responded. The company’s U.S. Ohm Laboratories site in New Jersey is manufacturing the drug (Also see "At Last, Ranbaxy Gets Valsartan Ok From U.S. FDA; Now The Wait Is For Nexium And Valcyte (Update)" - Scrip, 26 Jun, 2014.).
FDA’s Jane Axelrad, Center for Drug Evaluation and Research Associate Director for Policy, sent Hyman, Phelps attorneys a letter on Oct. 31 saying the agency has been unable to reach a decision on their petition requesting that it find Ranbaxy has forfeited exclusivity for any ANDA subject to the agency’s application integrity policy.
“FDA has been unable to reach a decision on your petition because it raises complex issues requiring extensive review and analysis by agency officials,” Axelrad stated.