News and Views: Evidence based prescription opioids, Additional tropical diseases for PRV, Quality Metrics Site Visit Program, Placebo controlled oncology clinical trials


New steps to advance the development of evidence-based, indication-specific guidelines to help guide appropriate prescribing of opioid analgesics

Need to reexamine how opioid analgesics are being prescribed

  • Arm health care providers with the most current and comprehensive guidance on  appropriate pain management
  • Work together with medical professional societies to develop  evidence-based guidelines

Contract with National Academies of Sciences, Engineering, and Medicine (NASEM)

  • Advance development of evidence-based guideline and understand needed evidence
  • Identification and prioritization of procedures and conditions associated with acute pain for which opioid analgesics are commonly prescribed
  • Scan existing opioid analgesic prescribing guidelines, how developed, gaps in evidence
  • Outline research needed to generate that evidence
  • Meetings and public workshops with broad range of stakeholders



FDA Adds Four Tropical Diseases to Priority Review Voucher (PRV) Program to Encourage Development

Addition of: 

  • Lassa fever
  • Chikungunya virus disease
  • Rabies
  • Cryptococcal meningitis

Applicants who submit drug/biological products applications may qualify for a  Priority Review Voucher (PRV)

  • Can be used to obtain priority review of a subsequent drug application that does not itself qualify for priority review




Quality Metrics Site Visit Program for CDER & CBER; Information Available to Industry; Extension of the Proposal Period

Quality Metrics Site Visit Program for FDA staff involved in development of FDA’s Quality Metrics Program

  • Gain exposure to robust quality metrics programs
  • Through on-site visits, tours of operations, discussions
  • Observe how quality metrics data are gathered, collected, reported to management

The intended timeframe of the on-location Quality Metrics site visits is from October 1, 2018 to  September 30, 2019



Hematologic Malignancy and Oncologic Disease: Considerations for Use of Placebos and Blinding in Randomized Controlled Clinical Trials for Drug Product Development

Placebo-controlled design only in selected circumstances

  • where surveillance is standard of care
  • with certain trial design features (e.g. if the trial uses an add-on design, when the
    endpoint intended to support a labeling claim has a high degree of subjectivity, such as patient reported outcomes


  • Rationale for the trial design
  • Justification in the setting of  sham surgical procedure or when invasive methods required for administration of the placebo (e.g., intrathecal administration, repeated 78 intravenous administration via an indwelling catheter)
  • No requirement of  patient-level maintenance of blinding at time of disease
  • Unblinding patient at time of documented disease recurrence or progression to ensure optimal patient management


Image credit: FDA

Public Meeting – Pediatric Medical Device Development – August 13-14, 2018, FDA White Oak Campus


Pediatric Medical Device Development –FDA Public Meeting 8/13/18

Medical device development for children lagged behind that for adults. FDA workshoop held to identify strategies that enhance the medical device ecosystem toward development and innovation of devices that serve the complex needs of children, and thereby accelerate medical device innovation for all Americans.


  • Need to improve research infrastructure and research networks to the conduct of clinical studies of pediatric devices, appropriately use extrapolation under section 515A(b), enhance the appropriate use of post-market registries and data to increase pediatric medical device labeling,  increase FDA assistance to medical device manufacturers in developing devices for pediatric populations that are approved or cleared, and labeled, for their use; and finally identify current barriers to pediatric device development and incentives to address such barriers. (identify current barriers and incentives)
  • FDA plan to dedicate in promoting timely access to safe and effective medical devices for all patients, and recognizes the unique needs of pediatric patients, despite a recognized need, relatively few medical devices have pediatric-specific indications and labeling
  • Increase availability of safe and effective pediatric devices by providing a roadmap for leveraging relevant existing clinical data for use in premarket approval applications (PMAs), humanitarian device exemptions (HDEs), and de novo request
  • Explain circumstances in which the FDA believes it may be appropriate to leverage existing clinical data to support pediatric device indications and labeling
  • Outline the approach FDA uses to determine whether extrapolation is appropriate, and if so, to what extent the data can be leveraged
  • Describe suggested statistical methodology that may be used to leverage the data in a way that increases precision for pediatric inferences
  • Incentives to increase investor interest and reimbursement success

Appropriateness of data extrapolation can be considered separately for effectiveness and safety 

  • Full extrapolation: existing clinical data may be used directly for prospective pediatric clinical data
  • Partial extrapolation: existing data are combined via a statistical model with pediatric data sources or prospective pediatric clinical data
  • Partial extrapolation permits utilization of existing clinical data to support demonstration of device safety or effectiveness for use in pediatric patients, with the expectation that some pediatric data are necessary
  • FDA comment about data extrapolation:  Extrapolated data may be used, not necessarily mean the data will support an approval decision

FDA Commissioner stated: we’re committed to supporting the development and availability of safe and effective pediatric medical devices, and to encourage device innovation for medical conditions that impact young populations.  Pediatric Device Consortia Grant Program and the Humanitarian Device Exemption pathway have helped foster the approval of a number of pediatric-specific medical devices and devices with a pediatric indication.

Workshop Information

Authorizations: ONPATTRO, NATURAL CYCLES Mobile Medical App, BONEBRIDGE Hearing System, GALAFOLD, ANNOVERA vaginal system


ONPATTRO (patisiran) infusion 

Alnylam Pharmaceuticals

INDICATION: Treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults (hATTR)


  •  First FDA-approved treatment for patients with polyneuropathy caused by hATTR, a rare, debilitating and often fatal genetic disease
  • Characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart and other organs
  • Also first FDA approval of new class of drugs called small interfering ribonucleic acid (siRNA) treatment

MECHANISM OF ACTION: Silencing portion of RNA involved in causing the disease  by encasing siRNA into lipid nanoparticle to deliver drug directly into the liver to alter or halt the production of disease-causing proteins


  • Randomized, double-blind, placebo-controlled, multicenter clinical trial, n=225  adult patients with polyneuropathy caused by hATTR amyloidosis,  ONPATTRO vs. placebo (N=77), 18 months
  •  Primary efficacy endpoint: Change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7);  objectively measures deficits in cranial nerve
    function, muscle strength, and reflexes, and the +7 assesses postural blood pressure, quantitative sensory testing, peripheral nerve electrophysiology
  •  Clinical meaningfulness assessed by change from baseline in Norfolk
    Quality of Life-Diabetic Neuropathy (QoL-DN) total score (patient reported
  • Both changes significantly favored ONPATTRO


  • Most common adverse reactions: infusion-related reactions including flushing, back pain, nausea, abdominal pain, dyspnea, headache
  • May also experience: vision problems including dry eyes, blurred vision and eye floaters (vitreous floaters)


  • Fast Track, Priority Review and Breakthrough Therapy designations. Onpattro also received Orphan Drug designation
  • Exempt from pediatric requirements
  • Postmarketing requirements: worldwide Pregnancy Surveillance Program
  • Postmarketing commitements: in vitro drug release, quality agreements



NATURAL CYCLES Mobile Medical App

Natural Cycles Nordic AB.

INDICATION FOR USE:  Stand-alone software application, intended for women 18 years and older, to monitor their fertility. Natural Cycles can be used for preventing a pregnancy (contraception) or planning a pregnancy (conception)


  • Consumers increasingly using digital health technologies to inform everyday health decisions
  • First Direct to Consumer App provides effective method of contraception if used carefully and correctly


  • Over-the-counter web and mobile-based standalone software application
  • Monitors menstrual cycle using information entered by the user and informs the user about her past, current and future fertility status
  • Following information entered by user
    • Daily basal body temperature (BBT) measurements
    • Menstruation cycle (i.e., start date, number of days)
    • Optional ovulation or pregnancy test results
  • Proprietary algorithm evaluates data and returns user’s fertility status
  • Three modes: Contraception, Conception, and Pregnancy

GENERIC DEVICE TYPE: Software application for contraception

  • Device that provides user-specific fertility information for preventing a pregnancy. This device includes an algorithm that performs analysis of patient-specific data (e.g., temperature, menstrual cycle dates) to distinguish between fertile and non-fertile days, then provides patient-specific recommendations related to contraception


  • Clinical studies  involved 15,570 women, used app for 8 months
  • “Perfect use” failure rate of 1.8%,
  • “Typical use” failure rate of 6.5%
  • Risk & Mitigation: Unintended pregnancy – Software verification, validation, and hazard analysis; Clinical performance testing; Human factors and usability testing; Labeling


  • New Regulation No.: 21 CFR 884.5370
  • Classification: Class II
  • Product Code: PYT



BONEBRIDGE Hearing System

MED-EL Elektromedizinische Geraete GmbH

INDICATION FOR USE:  Bone conduction hearing implant system for:

  • Patients 12 years of age or older
  • Patients who have a conductive or mixed hearing loss and still can benefit from sound amplification
  • The pure tone average (PTA) bone conduction (BC) threshold (measured at 0.5, 1, 2, and 3 kHz) should be better than or equal to 45 dB HL
  • Bilateral fitting of the BONEBRIDGE is intended for patients having a symmetrically conductive or mixed hearing loss
  • The difference between the left and right sides’ BC thresholds should be less than 10 dB on average measured at 0.5, 1, 2, and 3 kHz, or less than 15 dB at individual frequencies
  • Patients who have profound sensorineural hearing loss in one ear and normal hearing in the opposite ear (i.e., single-sided deafness or “SSD”)
  • The pure tone average air conduction hearing thresholds of the hearing ear should be better than or equal to 20 dB HL (measured at 0.5, 1, 2, and 3 kHz)
  • Any patient who is indicated for an airconduction contralateral routing of signals (AC CROS) hearing aid, but who for some reason cannot or will not use an AC CROS
  • Prior to receiving the device, it is recommended that an individual have experience with appropriately fit air conduction or bone conduction hearing aids.

GENERIC TYPE OF DEVICE: Active implantable bone conduction hearing system

  • Prescription device consisting of an implanted transducer, implanted electronics components, and an audio processor. The active implantable bone conduction hearing system is intended to compensate for conductive or mixed hearing losses by conveying amplified acoustic signals to the cochlea via mechanical vibrations on the skull bone


  • Dural erosion or compression, surgical complications, device software failure, implant failure, interference, adverse tissue reaction, infection



GALAFOLD (migalastat) capsule

Amicus Therapeutics

INDICATION: Treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data

  • Approved under accelerated approval based on reduction in kidney interstitial
    capillary cell globotriaosylceramide (KIC GL-3) substrate
  • Continued approval  contingent upon verification and description of clinical
    benefit in confirmatory trials


  • Rare Fabry disease causes slowly progressive kidney disease, cardiac hypertrophy (enlargement of the heart), arrhythmias (abnormal heart rhythm), stroke, early death
  • Galafold differs from enzyme replacement in that it increases the activity of the body’s deficient enzyme

MECHANISM OF ACTION:  Pharmacological chaperone that reversibly binds to the active site of the alpha-galactosidase A (alpha-Gal A) protein (encoded by the galactosidase alpha gene, GLA), which is deficient in Fabry disease


  • Six-month, placebo-controlled clinical trial, n=45 adults with Fabry disease, 6 months, GALAFOLD vs placebo
  • Greater reduction in globotriaosylceramide (GL-3) in blood vessels of kidneys (as measured in kidney biopsy samples) with GALAFOLD


  • Most common adverse drug reactions: Headache, nasopharyngitis, urinary tract infection, nausea, pyrexia


  • Accelerated Approval, Priority Review, Orphan Drug Designation
  • Accelerated Approval requirements:
    • Randomized, double-blind, placebo-controlled clinical trial to verify and
      describe the clinical benefit in patients with Fabry disease
    • Prospective, longitudinal, observational study to evaluate efficacy and
      pharmacodynamic effects in patients with a confirmed diagnosis of Fabry disease and amenable, disease-causing GLA variants


Capture.JPGANNOVERA (segesterone acetate and ethinyl estradiol vaginal system)

Population Council, Inc.

INDICATION: For use by females of reproductive potential to prevent pregnancy


  • First vaginal ring contraceptive that can be used for an entire year

DESCRIPTION: Reusable donut-shaped (ring), non-biodegradable, flexible vaginal system, placed in vagina for three weeks followed by one week out of vagina, at which time women may experience a period (a withdrawal bleed). This schedule is repeated every four weeks for one year (thirteen 28-day menstrual cycles).


  • Three, open label clinical trials with healthy women ranging from 18 to 40 years of age
  • About two to four women out of 100 women may get pregnant during the first year they use Annovera
  • Most common side effects: (similar to those of other combined hormonal contraceptive products)- headache/migraine, nausea/vomiting, yeast infections, abdominal pain, dysmenorrhea (painful menstruation), breast tenderness, irregular bleeding, diarrhea, genital itching
  • Boxed Warning: Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive (CHC) use


  • Postmarketing studies: Risks of venous thromboembolism, effects of CYP3A modulating drugs and tampon use on pharmacokinetics
  • Part of FDA’s new pharmacovigilance system, Sentinel’s Active Risk Identification and Analysis (ARIA)


Image Credit: Alnylam, Natural Cycles, MED-EL, Amicus, Population Council

News and Views: Real World Data, CMS Blue Button Conference, Tech Companies and Healthcare Data Interoperability, Competitive Generic Therapy Approval


Use of real-world data (RWD) to enhance research efficiency and bridge evidentiary gap between clinical research and practice

  • Increasing accessibility of digital health data
  • Transition to electronic health records (EHRs)
  • Address rising costs and recognized limitations of traditional trials
  • Research collaborations with Flatiron Health and CancerLinQ for big oncology data
  • Need access to other large databases

FDA effort should be supported by CMS’ Blue Button 2.0 – see below


CaptureKeynote speaker, CMS Administrator Seema Verma, on  Blue Button 2.0 and the MyHealthEData initiative

  • Developers use Medicare claims data to facilitate cost-effective care
  • Aggregate genetic information, medical records, claims data and wearable data in one electronic health record people can share with doctors and researchers.
  • Release of Medicare Advantage data to speed interoperability between EHRs and PHRs
  • Plans to release Medicaid data next year
  • Among 600 companies partnering on Blue Button 2.0 initiative are Verily Life Sciences, Rush, Humetrix, Health Endeavors, Anthem, Massachusetts Institute of Technology, 23andMe, Medware, 3K Technologies

Blue Button

Capture.JPGTech Companies Joint Commitment to Improve Healthcare Data Interoperability

Amazon, Google, IBM, Microsoft, Oracle, Salesforce

  • Frictionless exchange of healthcare data
  • Open standards, open specifications, and open source tools
  • Actively engaging among open source and open standards



FDA approves first generic drug under new pathway aimed at enhancing market competition for sole source drugs

Potassium chloride oral solution USP

Apotex Inc

Several strengths of potassium chloride oral solution approved via  Competitive Generic Therapy (CGT) designation

  • New approval pathway
  • Expedite development and review of generic drug that lack competition

INDICATION: Treatment and prevention of hypokalemia (low potassium blood levels) in patients who are on diuretics, and when dietary management with potassium-rich foods is insufficient or diuretic dose reduction is not possible


  • Met approval standards that ensure an equivalent, high quality, safe and effective generic medicine
  • Review of manufacturing and packaging facilities


Image credits: JAMA, FDA. CMS

Authorizations: MAGTRACE/SENTIMAG Magnetic Localization System, SURPASS Flow Diverter, MOLECULIGHT i:X, POTELIGEO injection


Magtrace and Sentimag Magnetic Localization System

 Endomagnetics Inc.

INDICATION FOR USE: To assist in localizing lymph nodes draining a tumor
site, as part of a sentinel lymph node biopsy procedure, in patients with breast cancer undergoing a mastectomy. Magtrace™ is intended and calibrated for use ONLY with the Sentimag® system.


  • Sentinel lymph node biopsies are crucial for determining whether a patient’s breast cancer has spread and helping the provider determine the most appropriate course of treatment
  • System offers patients undergoing mastectomy an option for their sentinel lymph biopsy procedure that does not require the injection of radioactive materials


  • Sensitive magnetic sensing probe and base unit designed to detect small amounts of Magtrace, the magnetic tracer drug that is injected into breast tissue
  • Magtrace particles travel to lymph nodes, become physically trapped in them, facilitating magnetic detection of the lymph nodes
  • Following injection of Magtrace, the Sentimag probe is applied to the patients’ skin in areas closest to the tumor site containing the lymph nodes
  • Sensing of the magnetic particles is indicated by changes in audio and visual alerts from the base unit, enabling the surgeon to move the hand-held probe around the area of the lymph nodes, and locate the sentinel lymph node or nodes (if there are more than one)
  • Surgeon makes a small incision and removes the node, which is checked by a pathologist for the presence of cancer cell
  • Negative result: Suggests cancer has not spread to nearby lymph nodes
  • Positive result: May indicate cancer present in sentinel lymph node,  nearby lymph nodes and, possibly, other organs
  • Help determine stage of cancer and develop appropriate treatment plan


  • Trial of 147 patients with breast cancer, n=147, Sentimag System vs. control methodin sentinel lymph node detection ratw
  •  94.3% for Sentimag System vs. 93.5% for control
  • Overall, 98.0% same detection rate with both Sentimag System and control
  • Most common adverse event: Breast discoloration, cardiac disorder (bradycardia) and potential allergic reaction to the magnetic materials
  • Contraindication: Hypersensitivity to iron oxide or dextran compounds

REGULATORY PATHWAY: PMA, Combination Product

  • Product Code: PUV
  • Classification: III
  • Classification Name:  Lymph Node Location System during Sentinel Biopsy Procedure
  • Coordinated, cross-agency approach- Clinical review conducted by CDRH in consultation with CDER and with support from Oncology Center of Excellence. All other aspects of review and final product approval by CDRH


LABEL Part 2


Surpass Streamline Flow Diverter


INDICATION FOR USE: In the endovascular treatment of patients (18 years of age and older) with unruptured large or giant saccular wide-neck (neck width ≥ 4 mm or dome-to-neck ratio < 2) or fusiform intracranial aneurysms in the internal carotid artery from the petrous segment to the terminus arising from a parent vessel with a diameter ≥ 2.5 mm and ≤ 5.3 mm.


  • Self-expandable braided device preloaded into a delivery system. Each device is shipped sterile and labeled for single use only
  • Consists of the following major components: Surpass Flow Diverter (Implant),  Delivery Catheter, Pusher


  • Multi-center, prospective, non-randomized clinical study., n=180, follow-up at discharge, 30 days, 6 months, and 12-months post-procedure
  • Primary Safety endpoint: % experiencing neurologic death or major ipsilateral stroke through 12-months post-procedure
  • Major Effectiveness endpoint: % with complete (100%) occlusion (Raymond-Roy Class I) of the treated intracranial aneurysm without clinically significant stenosis
  •  62.8% achieved complete occlusion of their intracranial aneurysm within 1year post-procedure without re-treatment or clinically significant in-stent stenosis


  • Product Code: OUT
  • Classification: III
  • Generic Name: Intracranial Aneurysm Flow Diverter



MolecuLight i:X

MolecuLight Inc.

INDICATION FOR USE:  Handheld imaging tool that allows clinicians diagnosing and treating skin wounds, at the point of care, to:

  1. view and digitally record images of a wound, and
  2. view and digitally record images of fluorescence emitted from a wound when exposed to an excitation light

For prescription use only.

GENERIC DEVICE TYPE: Wound autofluorescence imaging device

Tool to view autofluorescence images from skin wounds that are exposed to an excitation light. The device is not intended to provide quantitative or diagnostic information


  • Classification: I
  • Product Code: QCR
  • Regulation Number: 21 CFR 878.4165
  • Regulation Name: Wound autofluorescence imaging device

IDENTIFIED RISKS: Electrical/mechanical/thermal, electromagnetic compatibility (EMC) and optical safety of the device, and the error in fluorescence detection from the wound.

  • No special controls



POTELIGEO (mogamulizumab-kpkc) injection 

Kyowa Hakko Kirin

INDICATION FOR USE: Treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy


  • Mycosis fungoides and Sézary syndrome are rare, hard-to-treat types of non-Hodgkin lymphoma
  • Fills an unmet medical need for these patients

MECHANISM OF ACTION: CC chemokine receptor type 4 (CCR4)-directed monoclonal antibody; CCR4 present in some cancern cells


  • Clinical trial, n=372 patients with relapsed MF or SS, Poteligeo vs. vorinostat
  • Progression-free survival:  Median 7.6 months vs. median 3.1 months


  • Most common side effects: Rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain and upper respiratory tract infection
  • Serious warnings:  Risk of dermatologic toxicity, infusion reactions, infections, autoimmune problems,  complications of stem cell transplantation that uses donor stem cells (allogeneic) after treatment with the drug


  • Priority Review and Breakthrough Therapy designation, Orphan Drug designation
  • Postmarketing Requirements: Characterize complications after allogeneic hematopoietic stem cell transplantation
  • Exempt from pediatric assessments


Image credit: Endomagnetics, Stryker, MolecuLight Inc., Kyowa Hakko Kirin

News and Views: 2018-2019 Flu season, Transmucosal immediate-release fentanyl products, Electronic health record data in clinical investigations, Continuous manufacturing technology, Nicotine replacement drug therapies


Influenza Virus Vaccine for the 2018-2019 Season

Flu vaccine lots for 2018-2019 season have been released by FDA and are available for distribution by the manufacturers

  • Afluria, Afluria Quadrivalent, Fluad, Fluarix Quadrivalent, Flucelvax Quadrivalent, Flublok Quadrivalent, FluLaval Quadrivalent, Fluzone Quadrivalent

Selected by FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC)

  • Reviewed and evaluated surveillance data related to epidemiology and antigenic characteristics of recent influenza isolates, serological responses to 2017-2018 vaccines, and the availability of candidate strains and reagents



Continued, careful oversight of the REMS associated with transmucosal immediate-release fentanyl products

FDA Public Meeting with Drug Safety and Risk Management Advisory Committee (DSARM) and the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC)

  • Review data from Risk Evaluation and Mitigation Strategy (REMS) with Elements to Assure Safe Use (ETASU) for transmucosal immediate-release fentanyl (TIRF) products
  • Discuss findings from assessments conducted by manufacturers and  additional data about their use patterns and adverse events
  • Provide transparency around effectiveness of the REMS and whether changes might be necessary.

Significant decline in prescribing of TIRF products since REMS  implemented

  • How the TIRF REMS has affected the prescribing patterns
  • How the TIRF REMS can better promote safe prescribing
  • Reliability of current trend information, and how to collect even more accurate data

READFDA Briefing Document


FDA issues policy to facilitate the use of electronic health record data in clinical investigations

Publication of Guidance entitled, “Use of Electronic Health Record Data in Clinical Investigations; Guidance for Industry.”

  • Recommendations for sponsors, clinical investigators, contract research organizations (CROs), institutional review boards (IRBs), and other interested parties on the use of electronic health record (EHR) data in FDA-regulated clinical investigations
  • Goal to modernize and streamline clinical investigations through the use of EHR data
  • Inclusion of real world data in clinical investigations
  • Advance  interoperability and integration of EHR and Electronic Data Capture systems.



FDA supports critical research to spur innovation for continuous manufacturing technology to support and advance drug and biologics development

Under Emerging Technology Program, FDA awarded three grants, to study and recommend improvements for continuous manufacturing of drugs and biological products, innovative monitoring and control techniques

  • Rutgers University: Implementation in Continuous Pharmaceutical Manufacturing
  • Massachusetts Institute of Technology: Smart Data Analytics for Risk Based Regulatory Science and Bioprocessing Decisions
  • Georgia Institute of Technology: Continuous Synthesis, Crystallization, and Isolation (CSCI) of an API: Process Model-Controlled Enzymatic Synthesis of Beta-Lactam Antibiotics



New steps the agency is taking to support the development of novel nicotine replacement drug therapies to help smokers quit cigarettes

Aim to significantly reduce the rate of tobacco-related disease and death

  • Nicotine replacement therapy (NRT) products regulated as new drugs, is a critical part of overall strategy on nicotine
  •  New kinds of NRTs – with different characteristics or routes of delivery – can offer additional opportunities for smokers to quit combustible tobacco
  • Nicotine Steering Committee has been evaluating new, evidence-based opportunities to advance therapeutic nicotine products for combustible tobacco product cessation

Two draft guidances aimed at supporting the development of novel, inhaled nicotine replacement therapies that could be submitted to the FDA for approval as new drugs

  1. Nonclinical testing of orally inhaled nicotine-containing drug products
  2. Framework for new potential clinically relevant outcomes for smoking cessation products


Image credits: FDA, CDC

Authorizations: ORILISSA, MULPLETA, AZEDRA, FREESTYLE LIBRE Glucose Monitoring System


ORILISSA (elogolix) Tablets


INDICATION: Management of moderate to severe pain associated with endometriosis

ADDRESSING UNMET NEED:  First FDA-approved oral treatment for management of moderate to severe pain associated with endometriosis in over a decade

MECHANISM OF ACTION:  Nonpeptide small molecule gonadotropin-releasing hormone (GnRH) receptor antagonist; causes  suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of ovarian sex hormones, estradiol and progesterone.


  • Two multinational double-blind, placebo-controlled trials, n=1686 premenopausal women with moderate to severe pain associated with endometriosis
  • Co-primary efficacy endpoints: (1) dysmenorrhea response at Month 3 and (2) non-menstrual pelvic pain response at Month 3
  • Daily self-assessment of their endometriosis pain using numeric rating scale (NRS)
  •  Statistically significant greater responses (mean decreases from baseline) vs. placebo
  • Statistically (p <0.001) significant reduction from baseline in NRS scores vs. placebo


  • Most common side effects: hot flashes or night sweats, headache, nausea, difficulty sleeping, absence of periods, anxiety, joint pain, depression and mood changes
  • Warnings and Precautions: Bone loss, reduced ability to recognize pregnancy, suicidal ideation and mood disorder, reduced efficacy if contraceptives


  • Priority Review
  • Pediatric Assessments: Waived -product does not represent meaningful therapeutic benefit over existing therapies for pediatric patients and is not likely to be used in a substantial number of pediatric patient
  • Postmarketing Requirements:  Prospective pregnancy registry to evaluate effects  on pregnancy  and maternal and fetal/neonatal outcomes


Capture.JPGMULPLETA (lusutrombopag) Tablets

Shionogi Inc.

INDICATION: Treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure

ADDRESSING UNMET NEED: Offers physicians and patients another choice beyond platelet transfusions as adult patients with CLD often undergo procedures that could put them at increased risk for bleeding

MECHANISM OF ACTION:  Thrombopoietin (TPO) receptor agonist; induces proliferation and differentiation of megakaryocytic progenitor cells from hematopoietic stem cells and megakaryocyte maturation


  • 2 randomized, double‐blind, placebo‐controlled trials; n=312 patients with chronic liver disease who were undergoing an invasive procedure
  • Major efficacy outcome was the proportion of patients who require no platelet transfusion prior to the primary invasive procedure
  • Statistically significant (p<0.0001) treatment difference vs, placebo


  • Most common adverse reaction: Headache
  • Warning and Precautions: Thrombotic/Thromboembolic Complications


  • Priority Review
  • Pediatric assessments: Waived as necessary studies are impossible or highly impracticable



AZEDRA (iobenguane I 131) injection

Progenics Pharmaceuticals

INDICATION: Treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy


  • First FDA-approved drug for this use in ultra-rare cancer
  • Has been shown to decrease the need for blood pressure medication and reduce tumor size in some patients

MECHANISM OF ACTION: I 131 labeled iobenguane; taken up and accumulates within pheochromocytoma and paraganglioma cells, and radiation resulting from radioactive decay of I 131 causes cell death and tumor necrosis


  • Single-arm, open-label, clinical trial, n=68 patients
  • Primary Endpoint: ≥ 50% reduction of all antihypertensive medications lasting for at least six months
  • Secondary Endpoint: Overall tumor response measured by traditional imaging criteria
  • 25%  experienced ≥ 50% reduction of all antihypertensive medication
  • 22% with overall tumor response


  • Most common severe side effects:  Lymphopenia, neutropenia, thrombocytopenia, fatigue, anemia, increased INR, nausea, dizziness, hypertension and vomiting
  • Warning about radiation exposure to patients and family members
  • Other warnings and precautions:  Myelosuppression, underactive thyroid, elevations in blood pressure, renal failure or kidney injury and inflammation of lung tissue (pneumonitis)


  • Priority review, orphan product, fast track status, and breakthrough therapy designation



FREESTYLE LIBRE Libre 14 Day Flash Glucose Monitoring System


INDICATION FOR USE:  Continuous glucose monitoring (CGM) device indicated for the management of diabetes in persons age 18 and older. It is designed to replace blood glucose testing for diabetes treatment decisions

The System detects trends and tracks patterns aiding in the detection of episodes of hyperglycemia and hypoglycemia, facilitating both acute and long-term therapy adjustments

Interpretation of the System readings should be based on the glucose trends and several sequential readings over time. The System is intended for single patient use and requires a prescription

Expanding indication to:

  • extend the sensor wear period to 14 days
  • reduce the sensor warm up time to 1 hour

ADDRESSING UNMET NEED: Longest-lasting self-applied personal blood sugar sensor on the market


  • Externally-worn glucose sensor that continuously measures glucose levels and displays values to the user in response to a user-initiated action (scan)
  • Provide on-demand glucose information to user for up to fourteen days (the life of each sensor)
  • Does not passively monitor glucose levels or provide messages, alarms or alerts in the absence of user-intiated action


  • Non-randomized, single arm, multi-center, prospective, pivotal, nonsignificant risk study, without controls
  • Primary endpoint: Accuracy performance evaluation vs. laboratory glucose analyzer during in-clinic sessions that spanned the wear period of the device (days 1, 4, 7 and 10)
  • Comparable to performance of current generation CGM systems; established accuracy across the claimed measuring range (40 to 500 mg/dL glucose), precision, 14 day wear period (following the 1 hour warm-up period) for the sensor, notifications (Glucose Messages), and number of readings displayed during the wear period
  • Possible adverse effects of inserting sensor and wearing adhesive patch: local erythema, local infection, inflammation, pain or discomfort, bleeding at the glucose sensor insertion site, bruising, itching, scarring or skin discoloration, hematoma, and adhesive irritation
  • Potential adverse effects associated with making diabetes treatment decisions when glucose values and rates of change provided by the device are inaccurate


  • Previous version marketed in the US since October 2017 under P160030


Image credits: AbbVie, Shionogi, Progenics, Abbott