FDA updates on Oncologic Diseases and NGS test use for HIV-1

Mlo Washington Report

FDA OHOP reorganizes, renamed office of oncologic diseases

The U.S. Food and Drug Administration’s (FDA) office responsible for reviewing applications for new and existing cancer therapies has reorganized and been renamed as part of modernization plans approved in September 2019. The Center for Drug Evaluation and Research (CDER) Office of Hematology and Oncology Products (OHOP) has been reorganized and renamed the Office of Oncologic Diseases (OOD).

The OHOP contained three clinical divisions and one nonclinical division: Division of Oncology Products 1 (DOP1), Division of Oncology Products 2 (DOP2), Division of Hematology Products (DHP), and Division of Hematology Oncology Toxicology (DHOT). The new OOD structure consists of six divisions:

  • DOP1 is re-named Division of Oncology 1 (DO1). 
  • SOP2 will be split into two divisions: Division of Oncology 2 (DO2) and Division of Oncology 3 (DO3).
  • DHP will be split into two divisions to review products intended to treat hematologic malignancies: Division of Hematologic Malignancies 1 (DHM1) and Division of Hematologic Malignancies 2 (DHM2). DHP’s review of products to treat non-malignant hematologic conditions will move to another office within CDER.
  • DHOT remains the same. 

DO1 will retain its responsibilities for products for breast, gynecologic and genitourinary cancers, as well as supportive care. DO2 will review products for thoracic and head and neck cancers, central nervous system cancers, pediatric solid tumors and rare cancers. DO3 will review products for gastrointestinal malignancies, melanoma and other advanced skin cancers and sarcomas.

DHM1 will be responsible for products for acute leukemia and myelodysplasia (includes myelodysplastic-myeloproliferative overlap syndromes), chronic myeloid leukemia and other myeloproliferative neoplasms with the term “leukemia,” blastic plasmacytoid dendritic cell neoplasm (BPDCN), conditioning regimens for DHM1 indications, graft versus host disease, tumor lysis syndrome, cytokine release syndrome and CAR-T neurotoxicity.

DHM2 will review for products for lymphoma, chronic lymphocytic leukemia, multiple myeloma and other plasma cell malignancies.

Products for non-malignant hematologic diseases and conditions that DHP previously covered will be reviewed in the newly formed Division of Non-malignant Hematology (DNH) in the Office of Cardiology, Hematology, Endocrinology and Nephrology (OCHEN).

The Regulatory Project Management Staff are reorganized under the newly formed Office of Regulatory Operations (ORO) within the CDER Office of New Drugs (OND). Regulatory project management staff supporting the OOD will be in the newly formed Division of Regulatory Operations – Oncologic Diseases (DRO-OD), with individual branches supporting each of the five clinical review divisions in the OOD.

First NGS test for detecting HIV-1 drug resistance mutations

The U.S. Food and Drug Administration (FDA) authorized marketing of a test to detect human immunodeficiency virus (HIV) Type-1 drug resistance mutations using next generation sequencing (NGS) technology. The Sentosa SQ HIV Genotyping Assay is the first HIV drug resistance assay that uses NGS technology that the FDA has authorized for marketing in the U.S.

The current standard of care for patients with HIV-1 is antiretroviral therapy, also known as ART, the daily use of a combination of drugs to treat HIV by suppressing the virus. According to the NIH, it is a lifesaving treatment that can let patients with HIV lead long and healthy lives but it is not a cure.

Traditionally, monitoring a patient’s viral load has been done to evaluate the effectiveness of treatments. Increasing viral loads indicate that the virus may have mutated and that a patient’s current regimen is no longer effective at suppressing the virus. Once the virus has mutated and drug resistance develops, a person generally must change medications as different drugs will be needed to keep the virus from multiplying.

The Sentosa SQ HIV-1 Genotyping Assay detects HIV-1 drug resistance mutations in patients taking or about to start antiviral therapy. This assay detects mutations in genes of the HIV-1 virus from a sample of a patient’s blood using NGS. Understanding the mutations in the virus can help healthcare providers select an effective combination of drugs in an ART regimen and indicate which drugs may no longer be effective against the mutated HIV-1 virus. The FDA reviewed data from performance studies, which demonstrated a greater than 95 percent sensitivity and specificity in detecting 342 HIV drug-resistant mutations and determined the Sentosa SQ HIV-1 Genotyping Assay provides a reasonable assurance of safety and effectiveness for its intended use.

The Sentosa SQ HIV Genotyping Assay is for use only in patients with HIV-1 who are about to start or already taking antiviral therapy and is not intended for diagnosing infection with HIV. Results of this test are intended to be used in conjunction with clinical observations, patient history and other laboratory evidence to make patient management decisions.

The FDA reviewed data for the Sentosa SQ HIV Genotyping Assay through the de novo premarket review pathway, a regulatory pathway for devices of a new type. Along with this authorization, the FDA is establishing criteria, called special controls, the requirements that test developers must meet for demonstrating accuracy, reliability and effectiveness of tests intended to identify virus mutations. These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for tests of this type. This action also creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) pathway, whereby devices can obtain clearance by demonstrating substantial equivalence to a predicate device. 

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