eChapter 2016: Goodman & Gilman Year in Review Biologics FDA Approvals

PART 2: OTHER NOTEWORTHY (NONBIOLOGIC) APPROVALS AND REGULATORY ACTIONS

In 2016 the U.S. Food and Drug Administration (FDA) approved 22 new small-molecule drugs and granted 32 noteworthy biologic licenses. Among the 22 small molecules are:

• Six pharmacological "firsts" (see Part 1);

• Three diagnostic imaging agents for use with PET imaging (see Part 1);

• Three previously unapproved marketed drugs (ephedrine [Akovaz] injection,¹ tetracaine ophthalmic solution,² and methylene blue (Provayblue) injection (an orphan drug);³

• Two entities previously regulated only as dietary supplements (prasterone [dehydroepiandrosterone [DHEA]⁴ and vitamin B₂ [riboflavin]⁵; see eTable 6); and

• Eight new molecular entities that are pharmacologically similar to previously approved drugs (see eTable 5):

  1. Brivaracetam (Briviact):⁶ the second synaptic vesicle protein (SV2A) ligand to be marketed in the United States, it is an analogue of levetiracetam;

  2. Crisaborole (Eucrisa):⁷ the third FDA-approved phosphodiesterase 4 (PDE-4) inhibitor;

  3. Elbasvir and grazoprevir (Zepatier):⁸ was granted breakthrough therapy status for the treatment of chronic HCV genotype 1 infection in patients with end-stage renal disease on hemodialysis and for the treatment of chronic HCV genotype 4 infection⁹

     • Elbasvir is the third HCV NS5A protein inhibitor to win FDA approval (it is only marketed in a fixed-dose combination with grazoprevir under the brand name, Zepatier);⁸

     • Grazoprevir is the fifth HCV NS3/4A protease inhibitor to win FDA approval (it too is only marketed in a fixed-dose combination with elbasvir under the brand name, Zepatier);⁸

  4. Lixisenatide (Adlyxin);¹⁰ lixisenatide and insulin glargine (Soliqua 100/33):¹¹ lixisenatide is the fifth glucagon-like peptide-1 (GLP-1) receptor agonist to be marketed in the United States and the second GLP-1 receptor agonist to be marketed in a fixed-dose combination with a long-acting insulin (each 3-mL prefilled pen device contains 100 units/mL of insulin glargine and 33 mcg/mL of lixisenatide);¹¹

  5. Obeticholic acid (Ocaliva):¹² The fourth bile acid agent to marketed in the United States;

  6. Rucaparib (Rubraca):¹³ the second poly (ADP-ribose) polymerase (PARP) inhibitor to reach the U.S. market, it was designated by FDA as a breakthrough drug and approved in conjunction with the FoundationFocus CDxBRCA assay¹⁴ to detect the gene alterations in BRCA1 and BRCA2 necessary for patients to qualify to receive this new treatment¹⁵ (see Part 1); and

  7. Velpatasvir and sofosbuvir (Epclusa):¹⁶ Velpatasvir is the third HCV NS5A protein inhibitor to win FDA approval, it is marketed only in a fixed-dose combination with sofosbuvir, making it the second NS5A protein inhibitor/sofosbuvir combination to enter the U.S. market, but also the first for the treatment of all six genotypes of HCV.¹⁷

Part 1 looked back at first-in-class drug approvals; other breakthrough therapies and orphan indications; important new diagnostic tests; and novel medical devices. The noteworthy biologics approved in 2016 are described in Part 3. Throughout the series, orphan, breakthrough, and cancer therapy designations are notated by the symbols †, $, and #, respectively, and ...