FDA Continued Rejections of Citizen Petitions Highlights Key Lifecycle Challenges for Biologic Manufacturers
Citizen petitions have historically been a tool in the brand manufacturer’s toolkit of “product lifecycle management” but are fast becoming obsolete options due to mounting FDA resistance. A recent example of this came on January 5, 2018 when the FDA denied a citizen petition from Novo Nordisk aimed at blocking generic versions of its blockbuster insulin product Victoza® and two other liraglutide-containing products. Novo Nordisk and other brand biologic manufacturers are faced with the challenge of competing with a gathering wave of new biosimilar entrants and must respond accordingly if their franchises are to survive the onslaught. Given the FDA’s continued rejections of citizen petitions, manufacturers of brand biologics will have to embrace the hard task of developing robust brand defense strategies rather than trying to extend the clock with increasingly ineffective delay tactics.
The strategy behind Novo Nordisk’s citizen petition tactic is clear. Victoza® is the dominant GLP-1 in the market with $2.1 billion in 2016 US sales[i] and is set to lose patent exclusivity in 2022. With the threat of two biosimilars (so far) and other brands such as Trulicity® threatening to pry open Novo Nordisk’s grip on the market, the company is rightfully concerned with rapid market share erosion once biosimilar entry occurs. Consequently, Novo Nordisk and other brand biologic manufacturers are taking steps to protect or extend the value of their brand portfolios. One common tactic is to submit a 505(q) citizen petition to the FDA asking the agency to take specific action against a pending biosimilar application in the hopes that it will be delayed, suspended, or terminated altogether.
Novo Nordisk submitted its citizen petition in October 2017 asking the FDA to deny any ANDAs and abbreviated 505(b)(2) NDAs referencing its liraglutide-containing drugs (Victoza®, Saxenda®, and Xultophy®) without clinical comparative studies demonstrating a similar safety and efficacy profile to the reference listed drug[ii]. The petition cited the company’s own analytical comparison of its liraglutide drug to copies of the drug from two different suppliers and found impurity profiles that differed from its own. The company also maintained that the manufacturing process of the above products is so complex that equivalence of a biosimilar cannot be established without clinical trials. The FDA denied the petition on January 5, 2018 pointing to its October 2017 draft guidance on ANDA submission for synthetic peptides that reference a peptide of rDNA origin[iii]. The FDA denied the petition because Novo Nordisk’s petition demands were in excess of the draft guidance requirements. “This draft guidance, if finalized as written, would cover five peptide drug products, including liraglutide,” the FDA response letter stated.
Novo Nordisk is just one of many brand manufacturers to use this tactic. In 2015, Mylan tried to keep Teva from selling a generic version of the EpiPen by submitting a citizen petition[iv]. In 2016, AstraZeneca filed an eleventh-hour citizen petition to block generic entrants of its blockbuster cholesterol medication, Crestor[v]. Between 2006 and 2012, Shire ViroPharma filed 24 citizen petitions to delay the approval of generic versions of its antibiotic product Vancocin[vi]. According to the FDA’s most recent report to Congress on citizen petitions, the FDA received 74 citizen petitions related to pending generic and biosimilar applications in FY2015 alone[vii]. Not surprisingly, 92% of those petitions were from brand-name manufacturers, of which 90% were rejected. The FDA has come to recognize the use of citizen petition as nothing but a delay tactic and amended regulations last year such that the agency will no longer delay a generic or biosimilar entry solely because the originator filed a citizen petition[viii]. The FDA notes that it finds most citizen petitions to be without legitimate legal or scientific claims and the petition process continues to be manipulated, if not abused, for the sole purpose of delaying competitor entry.
[i] Novo Nordisk, Inc. (2016). Annual Report 2016. Available at https://www.novonordisk.com/content/dam/Denmark/HQ/AnnualReport/2016/PDF/Novo-Nordisk-Annual-Report-2016.pdf (Accessed on 1/22/2018)
[ii] Novo Nordisk, Inc. (2017). Citizen Petition. Available at https://www.regulations.gov/contentStreamer?documentId=FDA-2017-P-6029-0001&attachmentNumber=1&contentType=pdf. FDA Division of Dockets Management.
[iii] Food and Drug Administration (2018). Response Letter from FDA CDER to Novo Nordisk, Inc. Available at https://www.regulations.gov/document?D=FDA-2017-P-6029-0022. FDA Division of Dockets Management.
[iv]Mylan Specialty (2015). Citizen Petition. https://www.pharmamedtechbi.com/~/media/Supporting%20Documents/The%20Pink%20Sheet%20DAILY/2015/January/Citizen_Petition_Mylan_Specialty_epinephrine%20autoinjector%20ANDA.pdf. FDA Division of Dockets Management.
[v] AstraZeneca Pharmaceuticals. (2016). Citizen Petition. https://www.regulations.gov/contentStreamer?documentId=FDA-2016-P-1485-0001&attachmentNumber=1&contentType=pdf. FDA Division of Dockets Management.
[vi] Federal Trade Commission. (2017). FTC Charges That Shire ViroPharma Inc. Abused Government Processes Through Serial, Sham Petitioning to Delay Generics and Maintain its Monopoly over Vancocin HCl Capsules. https://www.ftc.gov/news-events/press-releases/2017/02/ftc-charges-shire-viropharma-inc-abused-government-processes. Accessed on 1/22/2018
[vii]Food and Drug Administration. (2016). Eighth Annual Report on Delays in Approvals of Applications Related to Citizen Petitions and Petitions for Stay of Agency Action for Fiscal Year 2015. https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ReportsBudgets/UCM517279.pdf.
[viii]Food and Drug Administration. (2016). Amendments to Regulations on Citizen Petitions, Petitions for Stay of Action, and Submission of Documents to Dockets. https://www.federalregister.gov/documents/2016/11/08/2016-26912/amendments-to-regulations-on-citizen-petitions-petitions-for-stay-of-action-and-submission-of.