FDA Approvals: TREMFYA, NERLYNX, VOSEVI, QUIKCLOT+ – Drug and Device Digest

FDA Brief: Week of July 17, 2017

FDA approved

TREMFYA (guselkumab) injection

Janssen Biotech, Inc.

INDICATION: Treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy


  • Required Pediatric Assessments: PK, Safety and Efficacy Study in pediatric subjects
    6 years to < 18 years with moderate to severe plaque psoriasis
  • Postmarketing requirements: Registry-based observational exposure cohort study on maternal, fetal, and infant outcomes of exposed pregnant women, claims or electronic medical record data or a case control study to assess adverse pregnancy outcomes

MECHANISM OF ACTION: Human monoclonal IgG1λ antibody, selectively binds to p19 subunit of interleukin 23 (IL-23), inhibits its interaction with the IL-23 receptor – inhibits release of proinflammatory cytokines and chemokines


  • Three multicenter, randomized, double-blind trials, n=1443 + 268, moderate-to-severe plaque psoriasis eligible for systemic therapy or phototherapy, TREMFYA vs. placebo or adalimumab, 16 weeks
  • Study 1 &2: Co-primary endpoints- Achievement of (i) Investigator’s Global Assessment (IGA) score of 0 (“cleared”) or 1 (“minimal”) and (ii) at least a 90% reduction from baseline in Psoriasis Area and Severity Index (PASI) composite score
  • 70%-80% vs. <10% response rate, maintained and durable for 48 weeks, greater improvements on Patient Reported Outcome based on Psoriasis Symptoms and Signs Diary (PSSD)
  • Study 3: TREMFYA vs. ustekinumab treatment; greater response with TREMFYA


  • Warnings and Precautions: Infections,  Tuberculosis (TB) – Evaluate for TB prior to initiating treatment
  • Most common (≥1%) adverse reactions:  Upper respiratory infections, headache, injection site reactions, arthralgia, diarrhea, gastroenteritis, tinea infections, herpes simplex infections


NERLYNX (neratinib maleate) Tablets

Puma Biotechnology, Inc.

INDICATION:  Extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab based therapy

ADDRESSING UNMET NEED: Personalized medicine


  • Postmarketing Requirements: Physiologically-based pharmacokinetic  modeling/simulation study on effect of repeat doses of a moderate CYP3A4 inhibitor, 2-year carcinogenicity study in the rat

MECHANISM OF ACTION: Irreversibly binds to Epidermal Growth Factor Receptor  (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4, inhibited activity of EGFR, HER2 and HER4


  • Single multicenter, randomized, double-blind, placebo-controlled trial,  n=2,840, early-stage HER2-positive breast cancer, NERLYNX vs. placebo, one year
  • Major efficacy outcome measure: Invasive disease-free survival (iDFS)  with 2 years and 28 days of follow-up; 94.2% vs. 91.9%  (HR 0.66; 95% CI: 0.49, 0.90, p=0.008)


  • Common adverse reaction leading to discontinuation: Diarrhea, Hepatotoxicity or increases in liver transaminases
  • Most common adverse reactions: Diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection


VOSEVI (sofosbuvir, velpatasvir, and voxilaprevir) tablet

Gilead Sciences, Inc.

INDICATION: Treatment of adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have:

  • genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV
  • regimen containing an NS5A inhibitor
  • genotype 1a or 3 infection and have previously been treated with an HCV regimen
    containing sofosbuvir without an NS5A inhibitor
  • Additional benefit of VOSEVI over sofosbuvir/velpatasvir (SOF/VEL)was not shown in adults with genotype 1b, 2, 4, 5, or 6 infection previously treated with sofosbuvir
    without an NS5A inhibitor


  • Estimated 2.7 to 3.9 million people in US with chronic HCV; may lead to liver cancer and death
  • At least six genetically distinct HCV genotypes or strain; 75% (genotype 1); 20-25% (genotypes 2 or 3), small number (genotypes 4, 5, 6)
  • First treatment approved for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A


  • Fixed-dose, combination tablet with two previously approved drugs – sofosbuvir and velpatasvir – and a new drug, voxilaprevir
  • Required Pediatric Assessments:  PK, safety and treatment response  in pediatric subjects 12 -18 years with chronic HCV genotype 1- 6
  • Postmarketing Requirement:  Assess signals of serious risk due to treatment-emergent resistance substitutions

MECHANISM OF ACTION: Combination of 3 drugs that are direct-acting antiviral (DAA) agents against the hepatitis


  • two trials in DAA-experienced subjects with genotype 1, 2, 3, 4, 5, or 6 HCV infection without cirrhosis or with compensated cirrhosis
  • VOSEVI vs Placebo or VOSEVI vs. SOF/VEL
  • Serum HCV RNA values measured using COBAS AmpliPrep/ COBAS Taqman HCV test,  lower limit of quantification (LLOQ) of 15 IU/mL
  • Primary Endpoint: Sustained virologic response (SVR12) – HCV RNA < LLOQ at 12 weeks; Relapse- HCV RNA >LLOQ; Virologic Failure- breakthrough, rebound, or non-response
  • 90-100% vs 0%  achievement of SVR12 in VOSEVI vs. placebo
  • 96% vs 85% achievement of SVR12 in VOSEVI vs. SOF/VEL


  • Most common adverse reactions: Headache, fatigue, diarrhea and nausea
  • Contraindication: Rifampin
  • Hepatitis B virus (HBV) reactivation: Need for screening


D2 Dressing (QuikClot+)

Z-Medica, LLC

INDICATION FOR USE: For temporary control of internal organ space bleeding for patients displaying class III or class IV bleeding. It may also be used for control of severely bleeding wounds such as surgical wounds and traumatic injuries

REG PATHWAY: De Novo request

  • Regulatory Classification: Class II
  • Product Code: POD
  • Non-absorbable, hemostatic gauze for temporary internal use
  • Intended to be placed temporarily for control of severely bleeding wounds such as surgical wounds and traumatic injuries. The gauze is coated or impregnated with a hemostatic material which may enhance hemostasis by physical means. The device is intended to be removed once the patient is stabilized.


  • Biocompatibility, performance bench, performance animal testing, clinical data on a previous formulation of the device (D1 Dressing)


  • Infection: Shelf Life Testing, Sterilization Validation, Labeling
  • Bleeding (Hemostasis Failure, Bleeding Recurrence): Animal Performance Testing, Technological Specifications
  • Vascular Obstruction (Ischemiam, Emboli Formation): Animal Performance Testing, Labeling
  • Adhesion Formation: Animal Performance Testing, Labeling
  • Adverse Tissue Reaction: Animal Performance Testing. Biocompatibility Evaluation
  • Device Retained in Body Leading to ReOperation: Animal Performance Testing, Non-Clinical Performance Testing, Labeling

Image Credits: Janssen, Puma, Gilead, Z-Medica

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