FDA approved


ARISTADA (aripiprazole lauroxil) extended-release injectable suspension, for intramuscular use

Indication: Treatment of schizophrenia

Unmet Need:

  • Schizophrenia is  chronic, severe, disabling brain disorder affecting ~ 1% Americans, mostly < 30 years old
  • Long-acting medications can improve the lives of patients
  •  Availability of  variety of treatment options and dosage forms important to tailor to patient’s needs

Reg Pathway : 505(b)(2). Application relied on investigations not conducted by or for the applicant and no right of reference


  • Leveraged efficacy data from approved oral aripiprazole, ABILIFY, Otsuka Pharmaceuticals
  • Additional data  12-week, randomized, double-blind, placebo-controlled, fixed-dose study (n=622) using Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Improvement Scale (CGI-I)
  • Demonstration of statistically significantly better PANSS and CGI-I scores versus placebo


  • Boxed Warning (Class labeling): Increased risk of death with off-label
  • Most common side effect  : Akathisia –  urge to move constantly

  • novocure OPTUNE – Device (Class III)


Portable, non-invasive device delivering low-intensity, intermediate frequency, alternating electric fields – referred to as Tumor Treating Fields (TTFields) – that inhibit cancer cell replication and cause cancer cell death.

Unmet Need:

  • 23,000 Americans diagnosed with brain or other nervous system cancers in 2015; >15,000 will die from them
  • 15 percent of all brain tumors -Glioblastoma Multiforme (GBM) – ages 45 to 70; highly resistant tumor, < 15 months survival
  • Need for new treatment option to increase survival

Reg Pathway : Priority Review of PMA supplement

Indication: Expanded indication for newly-diagnosed  GBM in combination with chemotherapy drug temozolomide (TMZ) following standard treatments that include surgery, and radiation therapy and chemotherapy used together.


  • A multinational, open-label, randomized Phase 3 trial (n=695) , Optune  + TMZ vs TMZ alone
  • Superior Progression-free Survival and Overall Survival. – study stopped early based on interim analysis
  • Survival : 19.4 months vs 16.6 months
  •  2-year survival rate  : 48% vs 32% (p=0.0058)

Safety: Skin irritation


FilmArray Meningitis/Encephalitis (ME) Panel


First cerebrospinal fluid (CSF) nucleic acid-based test for simultaneous detection of multiple pathogens that can cause central nervous system infections.   ME Panel uses CSF specimens from patients who have signs and/or symptoms of meningitis or encephalitis.

Unmet need: 

  • Meningitis and encephalitis are inflammatory diseases of the brain and spinal cord; caused by bacterial, viral or yeast infections;
  • Needs rapid treatment – otherwise can cause brain damage and can be fatal
  • ME Panel :
    •  Simple: 2 minutes of hands-on time
      • Easy: No precise measuring or pipetting required
      • Fast: Turnaround time of about 1 hour
      • Comprehensive: 14 bacterial, viral, and fungal targets

Reg Pathway : De novo classification process, a regulatory pathway for some low- to moderate-risk devices that are novel and not substantially equivalent to any legally marketed device.

Indication : Intended as aid in diagnosis of meningitis and encephalitis  when used in conjunction with other clinical and laboratory findings.

Clinical Performance:  Comparison of ME panel results vs other tests (including culture) demonstrated high level of agreement

  • CSF samples (n=1560)  with suspected meningitis/encephalitis
  • CSF Sample (n=150) previously determined to contain microorganisms
  • CSF samples (n=425) artificially prepared with specific concentrations of bacteria or viruses

intelesens Zensor wearable monitor for patients outside the hospital, 510 K Cleareance

  • zensorSmall, battery-powered device that clips on to an adhesive patch which also contains electrodes
  • Collects data on respiration rate, three-lead ECG, heart rate, and motion
  • Data sent via wifi to the cloud, allowing a clinician to access it on a smartphone, desktop computer, or tablet.

nfant NFant Feeding solution , 510 K clearance

nfant feeding

  • Monitor Progress During Feeding TransitionMeasures movement of the tongue on the nipple during pacifier and bottle sucking.
  • 100% PortableSmall NICU footprint. Integrates into normal clinical workflow; minimal setup.
  • User-friendlyFits most standard nipples, pacifiers, and bottles.

BMSOPDIVO (nivolumab) Targeting PD-1/PD-L1 pathway. Supplemental indication

Indication : Treatment for advanced (metastatic) non-small cell lung cancer (NSCLC) whose disease progressed during or after platinum-based chemotherapy.

Unmet Need: 

  • Lung cancer leading cause of cancer death in US; 221,200 new diagnoses and 158,040 deaths in 2015
  • NSCLC most common type of lung cancer, 2 types: Squamous cell and Non-squamous cell (which includes adenocarcinoma)
  • Opdivo blocks PD-1/PD-L1cellular pathway to enable immune system fight the cancer cells

Reg Pathway:

  • BreakThrough designation, Priority Review – Approval 3 months ahead of PDUFA goal!
  • Earlier approval treat advanced squamous NSCLC whose disease progressed during or after platinum-based chemotherapy. This approval expands treatment of non-squamous NSCLC.
  • Additional parallel approval of D-L1 IHC 28-8 pharmDx test (Dako North America Inc. in Carpinteria, CA) to detect PD-L1 protein expression


  • Open-label, randomized study (n=582);  Opdivo vs docetaxel
  • Primary endpoint : Overall Survival – 12.2 months vs 9.4 months
  • Secondary endpoint: Objective Response Rate (complete or partial shrinkage of their tumors). 19% (for 17 months) vs 12% (for 6 months)
  • Level of PD-L1 expression in NSCLC tumors may help identify patients who are more likely to live longer due to treatment with Opdivo. Use pharmDx test to determine potential responders


  • Most common side effects : fatigue, musculoskeletal pain, decreased appetite, cough and constipation
  • Serious  “immune-mediated side effects” on healthy organs, including the lung, colon, liver, kidneys, hormone-producing glands and the brain.

BIPRAXBIND (idarucizumab)

Indication : For use in patients who are taking the anticoagulant Pradaxa (dabigatran) during emergency situations when there is a need to reverse Pradaxa’s blood-thinning effects.  

Unmet need:

  • Pradaxa (anticoagulant) approved for stroke prevention in atrial fibrillation
  • Medical need for reversal of effect in some medical situations to control bleeding

Reg Pathway : Accelerate approval  ( approve drugs for serious conditions that fill an unmet medical need based on an effect on a surrogate or an intermediate clinical endpoint that is reasonably likely to predict a clinical benefit to patients)


  • 3 trials (n=283) healthy volunteers taking Pradaxa. Immediate reduction in the amount of Pradaxa in participants’ blood (measured as unbound dabigatran plasma concentration) that lasted for a period of at least 24 hours.
  • 1 trial (n=123)  patients taking Pradaxa, with uncontrolled bleeding or required emergency surgery. Full reversal of effect in 89% within 4 hrs.

Safety: Headache, low potassium (hypokalemia), confusion, constipation, fever and pneumonia.

FDA Voice

The Merging of Medical Products: Enhancing review of therapeutic and diagnostic combination products

By: Robert M. Califf, M.D. and Jill Hartzler Warner, J.D.

  • Combination products – new , novel approaches
  • Involve new, complex technologies – review  involves the expertise of more than one Center.

FDA Approaches:

◾Issuing more guidance for review of combination products (e.g., our pending draft guidance document on human factors);
◾Enhancing and simplifying data access and sharing for internal staff;
◾Making it easier for staff to request and monitor inter-center consults;
◾Updating and maintaining our internal contact directory for experts to review a combination product; and
◾Improving our internal standard operating procedures for premarket reviews and compliance activities.

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