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ONPATTRO (patisiran) infusion 

Alnylam Pharmaceuticals

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

ADDRESSING UNMET NEED:

  •  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

EFFICACY:

  • 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

SAFETY:

  • 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)

REGULATORY PATHWAY: NDA

  • 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

LABEL


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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)

ADDRESSING UNMET NEED:

  • 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

DESCRIPTION: 

  • 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

EFFECTIVENESS & SAFETY: 

  • 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

REGULATORY PATHWAY: De Novo request

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

CLASSIFICATION ORDER


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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

RISKS:

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

CLASSIFICATION ORDER


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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

ADDRESSING UNMET NEED:

  • 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

EFFICACY:

  • 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

SAFETY:

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

REGULATORY PATHWAY: NDA

  • 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

LABEL


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

Population Council, Inc.

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

ADDRESSING UNMET NEED:

  • 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).

EFFICACY & SAFETY:

  • 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

REGULATORY PATHWAY: NDA,  505(b)(2)

  • 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)

LABEL


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

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