Authorizations: ORAQUICK Ebola test, TRIKAFTA for cystic fibrosis, REYVOW for migraine, SCENESSE for erythropoietic protoporphyria

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ORAQUICK EBOLA RAPID ANTIGEN TEST 

OraSure Technologies, Inc

INDICATION FOR USE: In vitro diagnostic single-use immunoassay for the qualitative detection of antigens from viruses within the Ebolavirus genus but does not differentiate
between these viruses

ADDRESSING UNMET NEED: First rapid diagnostic test for the Ebola Virus Disease (EVD). The test provides a rapid, presumptive diagnosis that must be confirmed.

TYPE OF DEVICE: Device to detect antigens of biothreat microbial agents in human clinical specimens.

To detect antigens of biothreat microbial agents in human clinical specimens is  identified as an in vitro diagnostic device intended for the detection of antigens of microbial agents in specimens collected from patients with signs and symptoms of infection with biothreat microbial agents and who have been exposed to these agents or are suspected or at risk of exposure. The device can include antibodies for  immobilization and detection of the analyte. This device may also be used for cadaver testing to prevent human diseases for which cadavers constitute a source of human-to-human transmission.

EFFECTIVENESS AND SAFETY:  

  • Data from multiple clinical studies of blood samples and cadaveric oral fluid from the 2014 West African outbreak and analytical studies
  • Reasonable assurance of the safety and effectiveness when intended to identify antigens associated with Ebola virus in blood from symptomatic patients and oral fluid of cadavers – with high levels of Ebola virus
  • OraQuick Ebola Test is not intended to be used for general Ebola infection screening (e.g., airport screening) or testing of individuals at risk of exposure without observable signs of infection

REG PATHWAY: De Novo classification

  •  Emergency Use Authorization (EUA) pathway -Collaboration between FDA, WHO and Democratic Republic of Congo (DRC)
  • Breakthrough Device designation
  • Regulation Number: 21 CFR 866.4002
  • Regulation Name: Device to detect antigens of biothreat microbial agents in human clinical specimens
  • Regulatory Class: Class II
  • Product Code: QID

CLASSIFICATION ORDER


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 TRIKAFTA (elexacaftor/ivacaftor/tezacaftor) tablet

Vertex

INDICATION: Treatment of cystic fibrosis (CF) in patients aged 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one F508del mutation.

ADDRESSING UNMET NEED: First triple combination therapy available to treat patients with the most common cystic fibrosis mutation.

MECHANISM OF ACTION: Elexacaftor and tezacaftor bind to different sites on the CFTR protein to increase the amount of CFTR protein delivered to the cell surface. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of elexacaftor, tezacaftor and ivacaftor is increased quantity and function of F508del-CFTR at the cell surface, resulting in increased CFTR activity

EFFICACY:

  • 2 randomized, double-blind, active and placebo-controlled trials, patients with CF, 12 years and older
  • First trial – n=403 with F508del mutation and mutation on second allele  that is not responsive to ivacaftor or tezacaftor/ivacaftor alone
  • Second trial- n=107 patients with two identical F508del mutations
  • Primary analysis: Increases in % predicted forced expiratory volume in one second, (ppFEV1). Trikafta increased the ppFEV1 in both trials ( 13.8% from baseline vs.  placebo and 10% from baseline vs. tezacaftor/ivacaftor)

SAFETY:

  • Serious adverse drug reactions: Rash and influenza (flu) events
  • Most common adverse drug reactions: Headaches, upper respiratory tract infections, abdominal pains, diarrhea, rashes, increased liver enzymes (alanine aminotransferase and aspartate aminotransferase), nasal congestion, increased blood creatine phosphokinase, rhinorrhea, rhinitis, influenza, sinusitis and increased blood bilirubin
  • Warnings related to elevated liver function tests 

REG PATHWAY: NDA

  • Priority Review, Fast Track, Breakthrough Therapy, and orphan drug designation
  • Rare pediatric disease priority review voucher
  • Postmarketing requirements: Rat carcinogenicity studies, hepatic impairment study

LABEL


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REYVOW (lasmiditan)

Eli LIlly

INDICATION: Acute treatment of migraine with or without aura in adults.

ADDRESSING UNMET NEED: New option for the acute treatment of migraine that affects one in seven Americans

MECHANISM OF ACTION: Binds with high affinity to the 5-HT1F receptor; presumably exerts its therapeutic effects ithrough agonist effects at the 5-HT1F receptor

EFFICACY:

  • 2 randomized, double-blind, placebo-controlled trials, n=3,177 adult patients with history of migraine with and without aura, REYVOW vs, placebo
  • Primary Endpoint: % patients whose pain resolved and whose most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved two hours after treatment; significantly greater among patients receiving Reyvow.

SAFETY:

  • Risk of driving impairment
  • Most common side effects: Dizziness, fatigue, a burning or prickling sensation in the skin (paresthesia), sedation

REG PATHWAY: NDA

  • Controlled Substance scheduling by DEA pending
  • Required pediatric assessments
  • Postmarketing requirement: Maternal, fetal, and infant outcomes during pregnancy exposure

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SCENESSE (afamelanotide) implant

Clinuvel

INDICATION: To increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP)

ADDRESSING UNMET NEED: First treatment to increase pain-free light exposure in patients with rare disorder phototoxic reactions from EPP

MECHANISM OF ACTION: Synthetic tridecapeptide and a structural analog of α-melanocyte stimulating hormone – melanocortin receptor agonist and binds predominantly to melanocortin 1 receptor.

EFFICACY:

  •  2 parallel group clinical trials (n-93, 74), patients with erythropoietic protoporphyria, SCENESSE vs placebo
  • First trial primary endpoint: Total number of hours over 180 days spent in direct sunlight between 10 a.m. and 6 p.m. on days with no pain; . 64 hrs vs. 41 hrs
  • Second trial primary endpoint: Total number of hours over 270 days spent outdoors between 10 am and 3 pm on days with no pain for which “most of the day” was spent in direct sunlight; 6 hrs vs. 0.75 hrs

SAFETY:

  • Most common side effects: implant site reaction, nausea, oropharyngeal pain, cough, fatigue, skin hyperpigmentation, dizziness, melanocytic nevus , respiratory tract infection, somnolence, non-acute porphyria, skin irritation

REG PATHWAY: NDA

  • Priority Review, Orphan Drug designation
  • Postmarketing requirements: Thorough QT clinical study, Registry based observational exposure cohort study on long-term safety,

LABEL


Image credits: OraSure, Vertex, Eli Lilly, Clinuvel

 

 

News & Views: CDRH women health plan, ASCA, ALS guidance, Patient engagement, Limited Imodium packaging, Improving naloxone access, Premarket Tobacco Product Applications, Project Orbis

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CDRH: Health of Women Strategic Plan

  • Explores unique issues related to the performance of medical devices in women
  • Improves analysis and communication of sex- and gender-specific data to better assure the safe and effective use of medical devices
  • Develops and implements health science programs, strategies and initiatives focused on women’s health issues across CDRH

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The Accreditation Scheme for  Conformity Assessment (ASCA): Pilot Program

Under ASCA Pilot’s conformity assessment scheme, recognized accreditation bodies accredit testing laboratories for the competence of testing and calibration laboratories

  • ASCA-accredited testing laboratories may determine conformance of device with eligible standards
  • Provide declaration of conformity  to support  premarket submission

Scope

  • Development of the ASCA pilot
  • Conformity assessment resources leveraged in ASCA Pilot
  • Roles and Responsibilities: Accreditation bodies, Testing laboratories, Manufacturers, FDA staff
  • Selected Device Standards
  • Accreditation body and Testing Laboratory Participation

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Amyotrophic Lateral Sclerosis Guidance

ALS is progressive neurodegenerative disease that primarily affects motor neurons in cerebral motor cortex, brainstem, spinal cord, leading to loss of voluntary movement

  • Guidance focuses on specific clinical drug development and trial design issues that are unique to the study of ALS

Considerations

  • Early Phase Clinical Development, Population,  Effectiveness and Safety Considerations.
  • Specific Effectiveness Trial : Trial design, effectiveness endpoints,  timing of assessments, statistical considerations., prognostic factors,  integrated assessment of function and survival, Accelerated Approval considerations, Benefit-Risk considerations.

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Patient Engagement in the Design and Conduct of Medical Device Clinical Investigations

FDA values experience and perspectives of patients and their family caregivers. Draft guidance scope:

  • Use patient engagement to elicit experience, perspectives from patient advisors to improve design and conduct of medical device clinical investigations
  • Benefits of engaging with patient advisors
  • Patient engagement activities not considered by FDA to constitute research
  • Collecting and submitting patient engagement information

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Limited packaging for loperamide (Imodium) to encourage safe use

Reports of serious heart problems and deaths with much higher than the recommended doses of loperamide

  • Primarily among people intentionally misusing or abusing the product

To foster safe use of the over-the counter (OTC) anti-diarrhea drug loperamide

  • Use blister packs or other single dose packaging and to limit the number of doses in a package

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Continued efforts to increase availability of all forms of naloxone to help reduce opioid overdose deaths

Addressing opioid overdose continues to be one of the most urgent public health priorities

  • Naloxone is a critical tool for individuals, families, first responders and communities to help reduce opioid overdose deaths
  • Three FDA-approved forms of naloxone – injectable, auto-injector and nasal spray – require a prescription, which can be a barrier

Steps to improve access to naloxone (Narcan)

  • Pharmacists given direct authority to prescribe and sell naloxone to consumers
  • Community distribution and use by individuals with or without medical training
  • Approveal of first generic version of Narcan
  • Encouraging development of OTC naloxone products.

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Proposed rule for premarket tobacco product applications as part of commitment to continuing strong oversight of e-cigarettes and other tobacco products

Premarket tobacco product applications (PMTAs) for oversight of e-cigarettes and other tobacco products. Provide sufficient information on 

  • Physical aspects of a tobacco product
  • Potential public health benefits and harms
  • Also review tobacco product’s components, ingredients, additives, constituents, toxicological profile and health impact, as well as how the product is manufactured, packaged and labeled
  • Establish requirements for manufacturers to maintain records related to the legal marketing status of their tobacco products

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FDA takes first action under new international collaboration with Australia and Canada designed to provide a framework for concurrent review of cancer therapies

Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE), provides  framework for concurrent submission and review of oncology products among international partners

  • May allow cancer patients receive earlier access to drkugs
  • Greater uniformity of new global standards of treatment leading to the optimal design of  global clinical trials

First Project Orbis action in conjunction with the Australian Therapeutic Goods Administration and Health Canada

  • Accelerated approval to Lenvima (lenvatinib) in combination with Keytruda (pembrolizumab) for treatment of advanced endometrial carcinoma
  • Also used ‘Real-Time Oncology Review’ (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire clinical application

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Image credits: FDA, CDC

News & Views: AEDs, Office on New Drugs reorganization, New digital health policies, Office of Women’s Health, THC vapes warning

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Check Your AED: Is it FDA Approved?

Automated external defibrillators (AEDs) are portable, life-saving devices designed to treat sudden cardiac arrest,

  • Public access AEDs used by laypeople who have received minimal training
  • Professional use AEDs  used by first responders who receive additional AED training

Premarket approval (PMA) now required new and existing AEDs and necessary AED accessories batteries, pad electrodes, adapters and hardware keys for pediatric use)- deadline Feb 3, 2020

  • To ensure the quality and reliability
  • Needs sufficient valid scientific evidence to reasonably assure the device is safe and effective
  • Requires manufacturers to receive FDA approval before initiating design, manufacturing, or labeling changes to the device, imposes certain other annual reporting requirements.

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Reorganization of the Office of New Drugs with Corresponding Changes to the Office of Translational Sciences and the Office of Pharmaceutical Quality

To modernize the New Drugs Regulatory Program – a reorganization of the New Drugs Regulatory Program

Restructuring of the Office of New Drugs (OND) and corresponding changes in the Office of Translational Sciences (OTS) and Office of Pharmaceutical Quality (OPQ)

  • Create offices that align interrelated disease areas, and divisions with clearer and more focused areas of expertise
  • Enable greater efficiency, better understand the diseases, enhance scientific leadership

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New steps to advance digital health policies that encourage innovation and enable efficient and modern regulatory oversight

Guidances to continue to encourage innovative approaches to the development of digital health tools and advanced FDA oversight 

Clinical Decision Support Software, (revision)

  • Patients, families and health care professionals increasingly embracing digital health technologies to inform everyday decisions
  • Encourage developers to create, adapt and expand functionalities of software to support providers in diagnosing and treating diseases, while ensuring  no  unacceptable risk to patient
  • Focus our regulatory oversight on CDS functions intended to help health care professionals and patients inform their clinical management for serious or critical conditions- no independent evaluation of the basis of software’s recommendations

Changes to Existing Medical Software Policies Resulting from Section 3060 of the 21st Century Cures Act

  • Types of software that are no longer considered medical devices under the amended definition of device
  • Mobile apps that are intended only for maintaining or encouraging a healthy lifestyle – generally fall outside the scope FDA’s regulation

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Critical Focus on Women’s Health

Office of Women’s Health established in 1994  to advance health of women through science, policy, education, outreach, and inclusion of women in clinical trials

  • Investing in Women’s Health Through Engagement and Education 
  • Fostering Scientific Research and Filling Knowledge Gaps
  • Advancing Medical Therapies that Meet Women’s Needs

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FDA Warns Public to Stop Using Tetrahydrocannabinol (THC)-Containing Vaping Products and Any Vaping Products Obtained Off the Street

FDA strengthening warning to consumers to STOP using vaping products containing THC

  • More than 1,000 reports of lung injuries- including some resulting in deaths-following the use of vaping products
  • Most of the patients reported using THC-containing products, suggesting THC vaping products play a role in the outbreak

FDA Actions

  • Working closely with federal and state partners to identify the products or substances that may be causing the illnesses
  • FDA’s Forensic Chemistry Center using state-of-the-art technology to analyze hundreds of samples for the presence of a broad range of chemicals

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Image credit: FDA