eChapter 69 (Part 2): The Goodman & Gilman Year in Review: 2013 New and Noteworthy FDA Approvals

The FDA approved 40 new drugs and biologics of note in 2013. Eight are first-in-class agents indicated for the management of a variety of conditions (see part 1 of this series). Among the remainder are 22 newly approved drugs that are pharmacologically similar to others already marketed (see Table 69-3) and 10 new biologics. Although draft guidance on biosimilar product development was published by FDA in 2012, to date there have been no "follow-on biologics" approved in the U.S. under the new rules.¹ On another note, the FDA Safety and Innovation Act of 2012 had a dramatic impact on pediatric drug approvals in 2013.^2,3 The Act permanently reauthorized the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA).^4,5 Together, these two companion laws provide for an incentive (6 months of marketing exclusivity) and extend federal authority to enforce FDA requirements that drugs used in pediatric populations be reviewed for safety and efficacy. Supplemental pediatric indications were approved for at least 34 new and existing drugs and biologics in 2013.^{6,7,8,9,10,11} Other 2013 noteworthy FDA regulatory activities are summarized below. Table 69-4 lists established drugs that were "repurposed" for a new indication or significantly reformulated in 2013.

Antibiotics in Animal Feeds:

In 2013 FDA initiated a 3-year plan to phase-out the use of medically important antibiotics in animal feeds.¹² Antibiotics are widely added to packaged livestock feeds to improve feeding efficiency for the farmer by enhancing growth. The plan also calls for revoking the current over-the-counter status of veterinary antibiotics to bring them under the prescriptive oversight of veterinarians.¹²

Marketed, Unapproved Drugs:

2.5% and 10% phenylephrine eye drops were licensed in 2013. FDA approval of "marketed, unapproved" drugs establishes the good manufacturing practices necessary to assure their batch-to-batch reliability.¹³

Market Suspensions/Restrictions:

Ponatinib (ICLUSIG), a chemotherapy drug for leukemia, was temporarily suspended from the market in the U.S. in 2013 due to the emergence of life-threatening vascular complications (blood clots and narrowing of blood vessels). The marketing of ponatinib has resumed following labeling revisions, development of a Risk Evaluation and Mitigation Strategy (REMS), and initiation of post-marketing investigations sufficient to clarify the drug's benefit:risk ratio (see Ponatinib: Trials and tribulations of a fast-track drug in Goodman & Gilman Online Updates).¹⁴

Rosiglitazone (AVANDIA, AVANDAMET, AVANDARYL), an oral antidiabetic drug, had FDA-mandated marketing restrictions (in place since 2010) relaxed following confirmation of data that failed to show a heart attack risk in excess of the risk associated with metformin or sulfonylureas.^15,16

Phase-out of CFC-containing inhalers:

During 2013 FDA completed the two decades-long phase out of chlorofluorocarbon-containing inhalers by prohibiting the sale of the last remaining marketed CFC-containing inhaler, MAXAIR AUTOHALER (pirbuterol).¹⁷ Chlorofluorocarbons (CFCs) are known to decrease the protective ozone layer above the Earth and thereby increase the risks from sun exposure. The United States committed to phasing out CFC-containing inhalers under the terms of an international treaty (the Montreal Protocol on Substances that Deplete the Ozone Layer) entered into force on January 1, 1989. Today, 26 non-CFC inhalers are approved for marketing in the United States; many have been reformulated to contain hydrofluoroalkanes (HFAs) as propellants.

2013 Biologic Licenses:

Anti-inhibitor Coagulant Complex (FEIBA): Licensed for hemophilia A or B in patients who have developed inhibitors was extended to include prevention and prophylaxis.^18,19

Botulism antitoxin heptavalent [A, B, C, D, E, F, G], equine (BAT): Licensed as the first plasma derivative approved through the FDA's "Animal Rule" pathway.²⁰ The Animal Rule is used by FDA to judge the effectiveness of drugs and biologics in situations where it would be unethical to deliberately expose healthy human volunteers to a toxic biological, chemical, radiological, or nuclear substance. BAT is manufactured from horse plasma and is indicated for neutralizing all seven known botulinum nerve toxin serotypes.^21,22 The antitoxin will be maintained in the Strategic National Stockpile for distribution through the CDC's Drug Service.²²

Coagulation Factor IX [Recombinant)] (RIXUBIS): Licensed for the prevention and control of bleeding episodes in people with hemophilia B. Hemophilia B is caused by a mutation of the factor IX gene and leads to a functional deficiency of the gene product, coagulation factor IX.^23,24

Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted: Licensed for use in persons 18 years of age and older as a vaccine against avian influenza. This squalene-based "oil-in-water" adjuvanted (AS03) vaccine will be produced and distributed under contract to the U.S. Government as part of national pandemic preparedness initiatives.^25,26

Influenza Virus Vaccine (FLUBLOK): Licensed as the first influenza vaccine made using an insect virus (baculovirus) expression system and recombinant DNA technology. FLUBLOK offers an alternative formulation for patients with an allergy to egg proteins and is indicated for the prevention of seasonal influenza in people 18 through 49 years of age.^27,28

Influenza Virus Vaccine, Inactivated, Quadrivalent (FLUZONE QUADRIVALENT): Licensed as an extension of the FLUZONE product line (FLUZONE, FLUZONE HIGH DOSE, FLUZONE INTRADERMAL), quadrivalent influenza vaccine is indicated for the prevention of influenza in individuals 6 months of age and older. The quadrivalent vaccine contains 15 μg hemagglutinin antigen (HA) per virus strain (A/H1N1, A/H3N2, and two B antigens) per 0.5 mL, for a total of 60 μg HA per dose.^29,30

Pooled Plasma (Human), Solvent/Detergent Treated (OCTAPLAS): Licensed for the replacement of multiple coagulation factors in patients with acquired deficiencies due to liver disease or due to undergo cardiac surgery or liver transplant, and for plasma exchange in patients with thrombotic thrombocytopenic purpura.³¹

Prothrombin Complex Concentrate Human (KCENTRA): Licensed for use in conjunction with vitamin k for the urgent reversal of overanticoagulation by vitamin K antagonists.^32,33,34

Recombinant Coagulation Factor XIII A-subunit (TRETTEN): Licensed for the routine prophylaxis of bleeding in patients with congenital factor XIII A-subunit deficiency.^35,36

Technetium Tc 99m Tilmanocept (LYMPHOSEEK KIT): Licensed as a radioactive diagnostic agent indicated for lymphatic mapping, in conjunction with the use of a hand-held gamma counter, to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer or melanomas.^37,38