FDA BRIEF: Week of June 19, 2017
BAXDELA (delafloxacin) Tablets and Injection
INDICATION: Treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following:
Gram-positive organisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillinsusceptible [MSSA] isolates), Staphylococcus haemolyticus, taphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), Streptococcus pyogenes, and Enterococcus faecalis.
Gram-negative organisms: Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
ADDRESSING UNMET NEED: Antibacterial product treating serious or life-threatening infections
- Qualified infectious disease product (QIDP) under Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act
- Fast Track Designation, Priority Review
- Postmarketing Requirements: Surveillance for resistance, tissue distribution
MECHANISM OF ACTION: Fluoroquinolone class of antibacterial drugs, antibacterial activity due to inhibition of both bacterial topoisomerase IV and DNA gyrase
(topoisomerase II) enzymes for DNA replication, transcription, repair, recombination.
- 2 multicenter, multinational, double-blind, double-dummy, non-inferiority trials. (n=1510), adults with ABSSSI, BAXDELA vs. comparator (intravenous combination of vancomycin and aztreonam)
- Objective Clinical Response: 20% or greater decrease in lesion size determined by digital planimetry of the leading edge of erythema 48 to 72 hr post initiation.
- Investigator Assessment of response was made at Follow-up (Day 14 ± 1)
- Positive Clinical Response and Investigator Assessments in both trials
- Boxed Warning: Increased risk of disabling and potentially irreversible serious adverse reactions that have occurred together including tendinitis and tendon rupture, peripheral neuropathy, and central nervous system effects.
- Contraindication: Hyersensitivity to fluoroquinolones
- Adverse reactions: Nausea, diarrhea, headache, transaminase elevations (an enzyme that is an indicator of liver injury) and vomiting
HAEGARDA (C1 Esterase Inhibitor Subcutaneous [Human])
INDICATION: Plasma-derived concentrate of C1 Esterase Inhibitor (Human) (C1-INH) indicated for routine prophylaxis to prevent Hereditary Angioedema (HAE) attacks in adolescent and adult patients.
ADDRESSING UNMET NEED:
- HAE patients have absence or low levels of endogenous or functional C1-INH
- HAEGARDA replaces missing or malfunctioning C1-INH protein
- First C1-INH for subcutaneous administration for rare genetic disease
REG PATHWAY: BLA
- Orphan Drug Designation
DESCRIPTION: Human plasma-derived, purified, pasteurized, lyophilized (freeze-dried) concentrate prepared from large pools of human plasma from U.S. donors.
- A multicenter, randomized, double-blind, placebo-controlled, crossover study (n=90), 16-week treatment period, HAEGARDA (2 doses) vs placebo
- Efficacy Endpoint: Time-normalized number of HAE attacks (the rate of attacks) relative to placebo
- Significant decreases with both doses (p<0.001); median reduction 89%, 95%
- Responders (95% CI) with a ≥50% reduction vs placebo was 83% (73%, 90%)
- Significant decrease in time-normalized number of uses of rescue medication
- Most common side effects: Injection site reactions, hypersensitivity reactions, nasopharyngitis and dizziness
RITUXAN HYCELA (rituximab and hyaluronidase human) injection
INDICATION: For the treatment of Follicular Lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL)
Indicated for the following previously approved indications for Rituxan:
- Relapsed or refractory FL as a single agent
- Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
- Non-progressing (including stable disease), FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.
- Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.
- Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide (FC).
ADDRESSING UNMET NEED:
- Subcutaneous route of administration that shortens administration time to 5 to 7 minutes vs. several hours for intravenous infusion
- Provides for flat dosing.
REG PATHWAY: BLA
MECHANISM OF ACTION:
- Rituximab is monoclonal antibody targeting CD20 antigen and mediates B-cell lysis
- Hyaluronidase increases permeability of the subcutaneous tissue by temporarily depolymerizing hyaluronan
- Based on Pharmacokinetic (PK) results
- Non-inferior rituximab trough concentrations (Ctrough) levels for Rituxan Hycela 1,400 mg/23,400 Units compared to a intravenous rituximab 375 mg/m2
- NBon-inferior rituximab Ctrough levels for Rituxan Hycela 1,600 mg/26,800 Units compared to intravenous rituximab 500 mg/m2
- Comparable Overall Response, Progression Free Survival, Overall Survival Rates of Rituxan vs, Rituxan Hycela
- Boxed Warning: Severe mucocutaneous reactions, Hep B Virus reactivation, progressive multifocal leukoencephalopathy
- Most common adverse events: FL- infections, neutropenia, nausea, constipation, cough, and fatigue, DLBCL-infections, neutropenia, alopecia, nausea, and anemia, CLL- infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema
Image Credits: Melinta, CSL Behring, Genentech