On September 3, 2024, Eli Lilly filed a complaint against the FDA in the District Court for the Southern District of Indiana pursuing the latest challenge to the FDA’s application of its “biological product” classification. See Eli Lilly & Co. v. Becerra et al., No. 1:24-cv-01503 (S.D. Ind.). Lilly argues that the FDA improperly classified its retatrutide product as a drug, rather than as a biological product. Retatrutide is an investigational product which, according to Lilly, may have potential as an obesity treatment as well as a treatment for type-2 diabetes and other chronic conditions.
Under the Public Health and Service Act (PHSA), Congress amended the definition of “biological products” to include “proteins,” as well as products that are “analogous” to proteins. 42 U.S.C. § 262(i)(1). By regulation, the FDA has defined “protein” to mean “any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size.” 21 C.F.R. § 600.3(h)(6). “[T]he size of the amino acid polymer” is “based on the total number of amino acids” in the polymer, so long as the chains are “associated with each other in a manner that occurs in nature.” Id.
The FDA determined that retatrutide does not meet the definition of “protein” because it falls just short of the agency’s bright-line 40 amino acid length requirement. As described by Lilly, retatrutide has a backbone chain of 39 alpha amino acids connected via an isopeptide bond to a second backbone chain that has two or more amino acids: gamma-glutamate, which is an alpha amino acid, and 8-amino-3,6-dioxaoctanoic acid (ADO), which is not. Lily Compl. ¶ 37. The FDA determined that, under its regulatory definition, only alpha amino acids are counted towards the “greater than 40 amino acids” threshold. The FDA further concluded that retatrutide did not qualify as analogous to a protein either, because it did not share the “fundamental defining property of a protein” of “being greater than 40 alpha amino acids.”
In its suit against the FDA, Lilly challenges the FDA’s determination that only alpha amino acids should be counted in deciding whether an amino-acid chain is sufficiently long to meet the agency’s definition of “protein.” Alternatively, Lilly argues that retatrutide is at least “analogous” to a protein and thus should be classified as a biological product. According to Lilly, it is injured by the FDA’s classification decision because differences in regulatory treatment between drugs and biological products (related to approval standards, potential marketing exclusivities, and eligibility for compounding) have “substantial ramifications for Lilly at nearly every stage of retatrutide’s development, licensure, and marketing.” Compl. ¶ 87.
Lilly’s suit marks the third lawsuit against the FDA since 2020 challenging the agency’s decision to classify a product as a drug rather than a biological product. In Teva Pharms. v. FDA, 514 F. Supp. 3d 66 (D.D.C 2020), the district court upheld the FDA’s conclusion that Teva’s Copaxone was a drug rather than a biological product because it did not possess a specific, defined sequence. Most recently, in Ipsen Biopharmaceuticals, Inc. v. Becerra, 108 F.4th 836, 841 (D.C. Cir. 2024), the D.C. Circuit rejected a challenge to the FDA’s determination that Ipsen’s Somatuline Depot is a drug because its active ingredient, lanreotide acetate, contains only eight amino acids, notwithstanding that lanreotide self-assembles into more complex structures in the finished dosage form of the product.
Notably, the Ipsen decision was issued less than two weeks after the Supreme Court’s groundbreaking decision in Loper Bright Enterprises v. Raimondo, 144 S. Ct. 2244 (2024), which overruled the Chevron doctrine of judicial deference towards agency interpretations of ambiguous statutes. In this new lawsuit, Lilly argues that the Loper Bright decision supports its decision by foreclosing deference to the FDA’s understanding of the terms “protein” and “analogous.”
Lilly’s action is now pending before Judge Jane Magnus-Stinson of the Southern District of Indiana. A briefing schedule has not yet been set.
Stay tuned to Big Molecule Watch for further developments on this case.
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