FDA Brief, Weeks of Nov. 23 and 30, 2015 – Drug and Device Digest

FDA approved

BMSEMPLICITI (elotuzumab) for injection

Indication:  In combination with lenalidomide (Revlimid)  and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies

Unmet need:

  • Multiple myeloma form of blood cancer in  bone marrow
  • 26,850 new cases and 11,240 related deaths in the US in 2015
  • Need to therapies to provide additional benefit vs currently approved

Reg Pathway:  BLA, Breakthrough Designation, Priority Review, Orphan Drug Designation

Mechanism of Action:  Humanized IgG1 monoclonal antibody targeting  SLAMF7 (Signaling Lymphocytic Activation Molecule Family member 7)  expressed on myeloma cells and Natural Killer cells to mediate the killing of myeloma cells


  • Randomized open label (n=646); Empliciti + lenalidomide and  dexamethasone vs . lenalidomide and  dexamethasone
  • Progression-Free Survival : Hazard Ratio (95% CI) :0.70 [0.57, 0.85], p = 0.0004
  • Overall Response Rate : 252 vs.213, p = 0.0002
  • 1-and 2-year PFS rates :  68% and 41% vs. 57% and 27%, respectively



  • Most common side effects: Fatigue, diarrhea, fever (pyrexia), constipation, cough, nerve damage resulting in weakness or numbness in the hands and feet (peripheral neuropathy), infection of the nose and throat (nasopharyngitis), upper respiratory tract infection, decreased appetite and pneumonia


 Fluad (inactivated influenza vaccine containing adjuvant)

 Indication:   Aactive immunization against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine; approved for use in persons 65 years of age and older

Unmet Need:

  • 80 – 90 %  of seasonal influenza-related deaths & 50 – 70 %  of seasonal influenza-related hospitalizations occur in 65  years of age and older.
  • Need for immunizing in this age group; to decrease disease burden as well as  influenza-related hospitalizations and deaths

Reg Pathway: BLA, Accelerated Approval

Mechanism of Action:  Inactivated trivalent influenza vaccine,  containing hemagglutinin of influenza virus strains (two subtypes A and one type B), representing the  viruses likely to be circulating in the US  in  winter

Efficacy: Approval is based on the immune response; data demonstrating a decrease in influenza disease after vaccination  not available

  • Single study (n= 7,082) Fluad vs Agriflu (unadjuvanted vaccine)
  • Primary  immunogenicity analyses:Non-inferiority for all three vaccine strains for antibody levels


  • No safety concerns
  • Most common adverse events : Injection site pain and tenderness, muscle aches, headache and fatigue


lilly  Portrazza (necitumumab injection)

Indication: In combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer

Unmet need:

  • Lung cancer leading cause of cancer death in US
  • 221,200 new diagnoses and 158,040 deaths in 2015
  • Lung cancer tumors  varied, so need tailored treatment options to extend survival

Reg Pathway:   BLA, Standard Review

Mechanism of Action : Recombinant human lgG1 monoclonal antibody that binds to human epidermal growth factor receptor (EGFR) commonly found in lung cancer and blocks  malignant progression, induction of angiogenesis, and inhibition of apoptosis.


  • Multicenter, randomized, open-label (n= 1,093(, Portrazza + chemotherapy (gem + cis) vs chemotherapy alone
  • Overall Survival (median) : 11.5 mo. vs 9.9 mo. (p = 0.01)
  • Progression Free Survival (median) : 5.7 mo. vs 5.5 mo. (p=0.02_
  • No difference in Overall Response Rate


  • Most common side effects: Skin rash and magnesium deficiency (hypomagnesemia), which can cause muscular weakness, seizure, irregular heartbeats and can be fatal
  • Boxed Warning: Serious risks of  cardiac arrest and sudden death, as well as hypomagnesemia.


BMSOpdivo (nivolumab injection)

Indication : Treat advanced (metastatic) renal cell carcinoma  who have received prior anti-angiogenic therapy

Unmet need: 

  • Renal cell carcinoma is the most common form of kidney cancer
  • 61,560 new cases and 14,080 deaths from kidney and renal pelvis cancer in the US in 2015 .
  • Need for therapy to extend  survival ( Torisel, approve din 2007, only agent to extend survival)

Reg Pathway : Supplemental BLA, Breakthrough Therapy Designation, Fast Track Designation, Priority Review

Mechanism of Action: Human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor,releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.


  • Single open-label  randomized (n=821), Opdivo vs  everolimus
  • Overall Survival (median) : Median 25.0 mo. vs 19.6 mo. (p = 0.0018)
  • Complete or partial tumor shrinkage : 21.5 % (for 23 mo.) vs 3.9 % (for 13.7 mo)



  • Most common side effects : Abnormal weakness or lack of energy (asthenic conditions), cough, nausea, rash, difficulty breathing (dyspnea), diarrhea, constipation, decreased appetite, back pain and joint pain (arthralgia).
  • Serious  side effects :  “immune-mediated side effects” involve healthy organs, including the lung, colon, liver, kidneys, hormone-producing glands and the brain.


emergentBioThrax (Anthrax Vaccine Adsorbed)

Indication : Active immunization for the prevention of disease caused by Bacillus anthracis in persons 18 through 65 years of age.

Unmet Need: 

  • Anthrax disease, esp.inhalation form, is often fatal
  • Need for vaccine to prevent disease after exposure to anthrax spores (Post Exposure prophylaxis – PEP)

Reg Pathway:Supplemental BLA, FIRST  Approval  based on  Animal Rule.;  allows animal efficacy data to be used as a basis for approval when human efficacy studies are not ethical or feasible.

 10-year collaborative effort between Emergent, Biomedical Advanced Research and Development Authority (BARDA),  National Institute of Allergy and Infectious Diseases. A  2010 pre-Phase 3 Vaccines and Related Biological Products Advisory Committee meeting confirmed the regulatory pathway  

Mechanism of Action : Induces antibodies for  neutralizing the activities of the cytotoxic lethal toxin and edema toxin of Bacillus anthracis

Efficacy :

Animal Models : To derive protective antibody thresholds to bridge animal efficacy and human immunogenicity data and predict efficacy in humans.

  • Pivotal efficacy animal studies  in rabbits and nonhuman primates: Model developed for  70% probability of survival
  • 70-100% survival in animals receiving both  antimicrobial treatment and vaccination vs  antimicrobial treatment only

Human Studies : Safety and antibody responses

  • 200 healthy adults in three doses at zero, two, and four weeks;  antibody responses  correlated to a 70 percent probability of survival  observed in animal models.

Safety : Localized adverse events reported as tenderness, pain, swelling, and redness at the injection site, as well as limited movement of the injected arm. The most common systemic adverse reactions were muscle aches, headache, and fatigue


AngioJet™ ZelanteDVT™ Thrombectomy Catheter

510K Clearance, Boston Scientific

  • Use with the AngioJet Ultra Console to break apart and remove thrombus, including deep vein thrombus (DVT), from:
    • Iliofemoral and lower extremity veins ≥ 6.0 mm in diameter
    • Upper extremity peripheral veins ≥ 6.0 mm in diameter.
  • Infusion of physician specified fluids, including thrombolytic agents, into the peripheral vascular system.
  • NOT been evaluated for pulmonary embolism (PE)

algovitaAlgovita Spinal Cord Stimulation (SCS) System

510K Clearance, Nuvectra

  • Aid in the management of chronic intractable pain of the trunk and/or limbs, including unilateral or bilateral pain associated with failed back surgery syndrome, intractable low back pain, and leg pain.
  • 24-channel implantable pulse generators (IPGs)
  • Wireless clinician programmer with  computer-assisted stimulation programming to assist with effective and efficient localization, targeting and fine-tuning of pain coverage.




SilverCoat Silicone Foley Catheter

510K Clearance, Covalon Technology

  • Greater bacterial kill than two of the leading antimicrobial catheters
  • Minimizes biofilm formation and bacterial adherence
  • Kills pathogens most associated with CAUTI (Catheter Associated Urinary Tract Infections)




IQQA-Guide, an intra-operative 3D navigation system for thoracic, abdominal, and pelvic surgery

510K Clearance, EDDA Technology

  • Patient-specific anatomic models  extracted from multi-modality images for  3D navigation during surgery
  •  Surgeon can “see through” organ surfaces; may reduce use of intra-operative CT scans during imaging-guided surgical procedures

FDA Drug Safety Communication:

WARNING:  SGLT2 inhibitors for diabetes can cause too much acid in the blood and serious urinary tract infections

SGLT2 inhibitors


  • March 2013 – May 2015: 73 cases of ketoacidosis with hospitalization, 19 cases of life-threatening blood infections (urosepsis) and kidney infections (pyelonephritis)
  • May 2015 : Drug Safety Communication alert; continue to evaluate
  • Now :  Patients should stop taking their SGLT2 inhibitor and seek medical attention immediately if they have any symptoms of ketoacidosis. Health care professionals should assess for ketoacidosis and urinary tract infections in patients.  Label updated to include WARNING





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