The FDA ushered in six new drugs just before the close of 2014, bringing the final tally to 41– the highest rate since 1996, when the agency approved 53 drugs.
2014 drug approvals were notable not only for their quantity, but also their quality. A number of new drugs utilized first-in-class mechanisms, and new pathways always put a skip in our step here at WEEKLY headquarters. In this issue, we’ll delve into the science behind a few of our favorites.
PD-1 INHIBITOR DRUGS: WATCH YOUR BACK MELANOMA
The most closely watched drug development story of the year: the PD-1 inhibitor race from clinic to marketplace. PD-1 inhibitor drugs stop PD-1 protein function and represent a novel approach to fighting cancer.
Under healthy conditions, the PD-1 protein prevents the immune system from attacking the body it is charged with protecting. When PD-1 (found on T-cells) encounters a cell with PD-L1 proteins, it identifies that cell as self and tells the T-cell not to attack.
Under cancerous conditions, over-expressed PD-L1 cancer cells help tumors survive and thrive by evading T-cell detection. By inhibiting PD-1 (with the PD-1 inhibitor drug) no signal is sent to the T-cell, so the T-cell attacks the tumor.
Melanoma needs to watch its back, thanks to the approval of PD-1 inhibitors Keytruda (Merck, Whitehouse Station, NJ) and Opdivo (Bristol-Myers Squibb, New York, NY). PD-1 inhibitors are a platform therapeutic with potential broad spectrum application against many cancers. It is widely expected other PD-1 inhibitor drugs will gain approval for bladder, kidney, and non-small cell lung cancer indications.
BISPECIFIC ANTIBODIES: BEATING OUT LEUKEMIA
Amgen’s (Thousand Oaks, CA) Blincyto, for acute lymphoblastic leukemia, brings theory into practice with its “hybrid” monoclonal antibody (mAb) approach, known as a bispecific antibody. A bispecific antibody is composed of two fused mAb fragments, packing the power to bind a target cell on one arm and a therapeutic (or killing agent) on the other.
Blincyto redirects killer T-cells to target specific tumor cells. How? One arm grabs CD19, a protein found on the surface of blood cancer cells, and the other arm targets CD3, a protein that activates the T-cell receptor complex. Bringing the CD19 and CD3 together ensures killer T-cells are triggered to target the cancer cells. Activation also induces T-cell proliferation and the descendants of the activated T-cell also target the tumor cells. This novel mechanism, like PD-1 inhibition, will likely be adapted to fight a range of different cancers.
PARP INHIBITOR DRUGS: CANCER, MEET YOUR CELL DEATH
Programmed cell death, also known as apoptosis, drives the science behind AstraZeneca’s (London, UK) Lynparza for advanced ovarian cancer. This poly ADP-ribose polymerase inhibitor drug (PARP) enables damaging mutations to preferentially accumulate in cancer cells – triggering cell suicide.
Approved for patients with mutations in the DNA-repair enzymes BRCA1 and BRCA2, the drug works by inhibiting another DNA-repair enzyme, PARP1. With all three DNA-repair enzymes inactive, programmed cell death is triggered via the build-up of mutations in the rapidly dividing cancer cells.
NEW ANTIBIOTICS: SEALING THE GAP ON SKIN INFECTIONS
The FDA’s Generating Antibiotic Incentives Now program from 2012 grants qualified antimicrobials in development priority review and an additional five years of data exclusivity once approved. The result of this initiative? Three 2014 antibacterial medicine approvals: Dalvance (Actavis, Parsippany-Troy Hills, NJ), Sivextro (Cubist, Lexington, MA), and Orbactiv (The Medicines Company, Parsippany, NJ), all approved for skin infections.