AUTHORIZATIONS: ROZLYTREK for cancers with specific genetic defect, PRETOMANID for multidrug resistant TB, TURALIO for tenosynovial giant cell tumor, NUBEQA for castration resistant prostate cancer


ROZYLTREK (entrectinib)

Genentech, Inc.


  • ROS1-Positive Non-Small Cell Lung Cancer : Treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive.
  • NTRK Gene Fusion-Positive Solid Tumors: Treatment of adult and pediatric patients 12 years of age and older with solid tumors that:
    • have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation
    • are metastatic or where surgical resection is likely to result in severe morbidity, and
    • have either progressed following treatment or have no satisfactory alternative therapy.

Approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.


  • “Tissue agnostic” cancer treatment based on a common biomarker across different types of tumors rather than  body location
  • Innovation in precision oncology drug development, targeted and effective treatments
  • Simultaneous approvals in adult and pediatric populations

MECHANISM OF ACTION: Inhibitor of the tropomyosin receptor tyrosine kinases (TRK), proto-oncogene tyrosine-protein kinase ROS1, naplastic lymphoma kinase (ALK), JAK2 and TNK2. Inhibits tumorigenic potential through deactivation of downstream signaling pathways leading to constrained cell proliferation


  • Four clinical trials studying, n= 54 with NTRK fusion-positive tumors
  • Overall Response Rate (tumor shrinkage) of 57%; 7.4% having complete disappearance of the tumor; 61% with tumor shrinkage persisting for nine months or longer.
  • Most common cancer locations: Lung, salivary gland, breast, thyroid, colon/rectum

For non-small cell lung cancer,  with ROS1-positive and metastatic

  • Clinical studies, n= 51 with ROS1-positive lung cancer
  • Overall response rate: 78%, 5.9% with complete disappearance of cancer, 55% had tumor shrinkage persist for 12 months or longer


  • Most serious side effects: Congestive heart failure, central nervous system effects, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, vision disorders
  • Common side effects: Fatigue, constipation, dysgeusia, edema , dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, weight gain, cough, vomiting, fever, arthralgia, vision disorders


  • Accelerated approval. .Priority ReviewBreakthrough Therapy and Orphan Drug designation
  • Postmarketing requirements: Clinical studies that further characterize clinical benefit, functional activation or inhibition of off-target receptors, transporters, and/or channels, integrated safety analyses and supporting data, effect of moderate and severe hepatic impairment



The Global Alliance for TB Drug Development (TB Alliance)

INDICATION: Limited Population: Part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary extensively drug resistant (XDR) or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB).  Approval of this indication is based on limited clinical safety and efficacy data.

Indicated for use in limited and specific population of patients


  • Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options
  • estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB
  • New treatments are important to meet patient national and global health needs

MECHANISM OF ACTION: Nitroimidazooxazine antimycobacterial drug


  • Open-label study conducted in three centers in South Africa, n=109 with extensively drug-resistant, treatment intolerant or non-responsive multidrug-resistant pulmonary TB (of the lungs), taken orally in combination with bedaquiline and linezolid, 6 months
  • Endpoint: Incidence of bacteriologic failure (reinfection – culture conversion to positive status with different M. tuberculosis strain), bacteriological relapse (culture conversion to positive status with same M. tuberculosis strain), or clinical failure through follow-up until 6 months after the end of treatment
  • Successes (lack of failure) : 89%, significantly exceeded the historical success rates or treatment of extensively drug resistant TB


  • Most common adverse reactions:  Peripheral neuropathy, acne, anemia, nausea, vomiting, headache, increased liver enzymes, dyspepsia, rash, increased pancreatic enzymes, hypoglycemia, diarrhea


  • Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD)pathway
  • Qualified Infectious Disease Product (QIDP) designation, Priority Review, Orphan Drug designation
  • Awarded Tropical Disease Priority Review Voucher 


CaptureTURALIO (pexidartinib) capsules

Daiichi Sankyo

INDICATION: Treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery

ADDRESSING UNMET NEED: TGCT is a rare tumor that affects the synovium and tendon sheaths causing damage to surrounding tissue

MECHANISM OF ACTION: Tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R); inhibition of proliferation of cell lines dependent on CSF1R and ligand-induced autophosphorylation of CSF1R


  • Multi-center international clinical trial, n=120 patients, TURALIO vs. placebo
  • Primary efficacy endpoint: Overall response rate (ORR) analyzed after 25 weeks
  • Statistically significant improvement in ORR: 38% on TURALIO vs 0% on placebo
  • Complete response rate: 15%, Partial response rate: 23%


  • Boxed Warning: Risk of serious and potentially fatal liver injury. REMS program
  • Common side effects: Increased lactate dehydrogenase, increased aspartate aminotransferas, loss of hair color, increased alanine aminotransferase, increased cholesterol


  •  Breakthrough Therapy designation,  Priority Review designation, Orphan Drug designation
  • Postapproval commitments: Further evaluate the risk of hepatoxicity
  • REMS to prevent potentially fatal liver toxicity: To include (i) Communication Plan and (ii)  Elements to  Assure Safe Use


Capture.JPGNUBEQA (darolutamide) tablets


INDICATION: Treatment of patients with non-metastatic castration resistant prostate  cancer (nmCRPC)

MECHANISM OF ACTION: Androgen receptor (AR) inhibitor


  • Multicenter, double-blind, placebo-controlled clinical trial, n=1,509 patients with non-metastatic castration resistant prostate cancer, NUBEQA vs. placebo, all  received gonadotropin-releasing hormone (GnRH) analog concurrently or had previous bilateral orchiectomy
  • Primary endpoint: Metastasis free survival (MFS)
  • 40.4 months with darolutamide vs. 18.4 months with placebo,  p<0.0001


  • Most common adverse reactions: Fatigue, pain in extremity, and rash
  • Other: Ischemic heart disease, failure, seizures


  • Fast track designation, Priority Review


Image credits: Genentech, TB Alliance, Daiichi Sankyo, Bayer








News & Views: Novartis Data Accuracy Issues, e-cigarettes and seizures, Topical drugs bioequivalence, Drug safe importation


Data accuracy issues with Zolgensma, manufactured by AveXis (Novartis)

  • On May 24, the FDA approved Zolgensma, a gene therapy product intended to treat children less than two years of age with spinal muscular atrophy (SMA)
  • On June 28, the agency was informed by AveXis Inc (Novartis subsidiary), about  data manipulation issue of data submitted in the BLA for the approval
  • Thus FDA approved Zolgensma without knowledge of data manipulation; the Agency continues to be supportive of the benefit-risk profile at this time
  • However, the Agency is concerned about the delay in notification by Novartis
  • Ensuring truthful, complete and accurate data in product applications is a critical component of industry responsibility
  • There will be further inspections and investigations and will take action including civil or criminal penalties

FDA 483 Inspection Report


Capture.JPGSeizures following e-cigarette use as part of agency’s ongoing scientific investigation of potential safety issue

  • Continuing FDA scientific investigation on direct relationship between e-cigarettes and risk of seizure or other neurological symptoms
  • 127 reports on e-cigarette users experiencing seizures (between 2010-2019)
  • Some users reported other serious neurological symptoms e.g. fainting, tremors
  • FDA requesting use of Safety Reporting Portal   for any unexpected health or product issues experienced with e-cigarettes


Capture.JPGEvaluating bioequivalence for topical drugs

  • FDA research initiative to facilitate generic topical dermatological drug product development
  • New method for monitoring amount of topical drug in dermis using dermal open-flow microperfusion (dOFM)
  • Thin, hollow porous tube inserted just under the skin surface, liquid similar to body fluid is injected, any applied drug absorbed through the skin’s outer layer enters  flowing liquid, which is then collected for analysis
  • Clinical study performed to confirm dOFM could reliably measure changing amounts of drug in skin after topical application of dermatological drug products



 New Action Plan to Lay Foundation for Safe Importation of Certain Prescription Drugs

Two potential pathways for safe importation of certain drugs originally intended for foreign markets
  1. Pathway 1: Authorize importation of drugs from Canada with conditions to ensure  no additional risk to public’s health and safety
  2. Pathway 2: Import versions of FDA-approved drug products being sold in foreign countries that are the same as the U.S. versions; use a new National Drug Code
Safe Importation Action Plan – PDF*

Image credits: Novartis, FDA