July 2018

Features

FDA Posts First List of Surrogate Endpoints

July 30, 2018

The FDA has published the first-ever list of surrogate endpoints, giving sponsors the first concrete suggestions for the kinds of laboratory measures or physical signs that might help develop drugs even when clinically meaningful data proves elusive.

Briefs

FDA: Put Patients on Strict Diets in Trials for Metabolic Disorders

July 30, 2018

Sponsors studying genetic metabolic disorders should put patients on strict diets before clinical trials begin, the FDA says in a new draft guidance. Researchers have already developed drug treatments to complement the diets of people who suffer from such metabolic disorders as phenylketonuria, organic acidemia and urea cycle defects. But even small nutritional changes can affect clinical trial results, especially when a proposed drug’s impact is “relatively modest,” the FDA says. To address those challenges, the FDA recommends that participants in clinical trials be put on strict eating plans (that are clearly detailed) before studies start. While monitoring diets, sponsors should remember that the two most common assessments — food frequency questionnaires and food diaries — have limited value because they rely on “crude measures” and participant memory. The length of time participants spend on their pretrial diet should be based on their age, disorder (and its severity) and how complex the diet is, the guidance states. Patients with metabolic disorders often have to undergo surgeries, which, in turn, may require they go on specialized diets. Any surgeries should be completed well before a trial begins, the FDA says. The agency also discourages switchover trials in which patients are initially put on a special diet and then given a drug. “Without a concurrent control arm and blinding, switchover designs are unlikely to produce interpretable results,” the FDA says.Read the full guidance here: www.fdanews.com/07-23-18-Metabolism.pdf.

Trial Results

GSK’s ViiV Healthcare Presents Data of Trial for Treatment of HIV

July 30, 2018

GSK’s ViiV Healthcare presented results from the Phase III GEMINI 1 & 2 studies, assessing the safety and efficacy of a two-drug regimen (2DR) of dolutegravir (DTG) and lamivudine (3TC) compared to a three-drug regimen of dolutegravir and two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in treatment-naïve, HIV-1 infected adults. The studies are designed to demonstrate the non-inferior efficacy, safety and tolerability of once-daily dolutegravir and lamivudine compared to once-daily dolutegravir and the fixed-dose combination of TDF/FDC. GEMINI 1 (204861) and GEMINI 2 (205543) are duplicate, Phase III, randomized, double-blind, multicenter, parallel group, non-inferiority studies. These studies enrolled naïve adult participants with baseline HIV-1 viral loads up to 500,000 copies per ml. The studies met their primary endpoint for non-inferiority based on plasma HIV-1 RNA <50c/mL, a standard measure of HIV control, at Week 48. Results show broadly consistent results for virus suppression across individuals with higher viral load. Pooled results show that the most common (≥5 percent) adverse events across the studies were headache, diarrhea and nasopharyngitis in both arms (DTG + 3TC arm: 10 percent, 9 percent, and 8 percent, respectively, DTG + TDF/FTC: 10 percent, 11 percent, and 11 percent). Rates of virologic failure were ≤1 percent across all arms of the study. Drug-related adverse events were less frequent in patients on the DTG/3TC regimen (126/716, 18 percent), compared with those on the DTG + TDF/FTC regimen (169/717, 24 percent).

Pipeline

New Pipeline from Dermtreat, Allergan, Pfizer, and LifeSignals

July 30, 2018

Company Drug/Device Medical Condition Status
Tolero Pharmaceuticals, Inc. TP-0184, an activin A receptor type 1 (ACVR1) advanced solid tumors Phase I trial initiated
Sangamo Therapeutics, Inc. SB-318 mucopolysaccharidosis type I (MPS 1, Hurler syndrome) Phase I/II trial initiated enrolling up to 9 adult subjects
Dermtreat Rivelin Clobetasol patch (Rivelin-CLO) oral lichen planus (OLP) Phase IIb trial initiated enrolling 240 subjects
Biohaven Pharmaceutical Holding Company Ltd. trigriluzole (BHV-4157) mild-to-moderate Alzheimer’s disease (AD) Phase II/III trial initiated enrolling 292 subjects
MED-EL USA BONEBRIDGE bone conduction hearing implant system individuals 12 years and older who have been diagnosed with conductive hearing loss, mixed hearing loss or single-sided deafness De Novo clearance granted by the FDA
CarboFix Orthopedics LTD. CarboClear Fiber Pedicle Screw System patients with advanced-stage tumors involving the thoracic and lumbar spine in whom life expectancy is of insufficient duration to permit achievement of fusion 510(k) clearance granted by the FDA
Cepheid Xpert Xpress Flu/RSV test influenza A and B viruses 510(k) clearance granted by the FDA
Allergan plc AGN-241751 Major Depressive Disorder (MDD) Fast Track Designation granted by the FDA
Flashback Technologies CiperOx CRI M1 monitor detection and monitoring of acute blood loss Clearance granted by the FDA
LifeSignals LP1100 Life Signal Patch healthcare monitoring devices Clearance granted by the FDA
AbbVie and Neurocrine Biosciences, Inc. ORILISSA (elagolix) moderate to severe endometriosis pain Approval granted by the FDA
Ology Bioservices, Inc. and Rafa Laboratories Ltd. Atropine Autoinjector chemical nerve agent poisoning Approval granted by the FDA
Devicor Medical Products, Inc. Magtrace and Sentimag Magnetic Localization System (Sentimag System) for guiding sentinel lymph node biopsies breast cancer Approval granted by the FDA
Senseonics and Integrated Device Technology, Inc. Eversense Continuous Glucose Monitoring (CGM) System Diabetes Approval granted by the FDA
Pfizer Inc. NIVESTYM (filgrastim-aafi) neutropenia Approval granted by the FDA
Agios Pharmaceuticals ivosidenib (Tibsovo) specific gene mutation IDH1 found in patients with acute myeloid leukemia (AML) or those patients who have relapsed or do not respond to standard chemotherapy Approval granted by the FDA
Features

New Guidance for Multiregional Clinical Trials

July 23, 2018

The FDA has issued new guidelines designed to help researchers navigate sometimes conflicting regional requirements and differences in global clinical trials in an effort to pave the way for better cooperation and faster international drug development.

Features

New Report: Improving Clinical Site Payment Practices

July 23, 2018

Paying sites on time is critical to a trial’s success, sponsors agree, and most believe they’re making the grade. So why are sites so frustrated with how they’re paid? Are their expectations unreasonable or are sponsors operating in the dark?

Briefs

FDA Issues New Guides on Use of Electronic Health Information in Clinical Trials

July 23, 2018

The FDA is urging researchers to work with electronic health record keepers to help improve clinical trial accuracy and efficiency. The agency doesn’t typically regulate companies or organizations that maintain electronic medical records (EMRs). But it says it’s weighing in to highlight and clarify ways electronic health record (EHR) systems can help clinical trials run more smoothly and use data from foreign studies conducted outside investigational new drug applications and device exemptions. In guidelines released July 18, the FDA encourages sponsors and investigators to use approved EHR or electronic capture data capture (EDC) systems to exchange key information, noting that doing so can dramatically speed up information sharing and precision.

Other FDA tips:

  • Sponsors and investigators should use EHR systems endorsed by the Office of the National Coordinator for Health Information Technology (ONC). If they lack access to ONC-certified systems, they should make sure security measures are in place to protect study data.
  • Study monitors should have easy access to “all relevant information” detailed in consent forms, including how long identifying records will be kept. (Federal law requires investigators to keep records from drug or human biological product trials for at least two years after marketing applications have been approved or trials have been scrapped and the FDA notified. Records relating to medical devices must be retained for at least two years after an investigation wraps up or after it’s determined they are no longer needed to support premarket approval applications or notices of completion.)

Read the FDA’s guidance here: https://www.fdanews.com/07-18-18-HealthRecordData.pdf.

Pipeline

New Pipeline from Adaptiiv, Zavation, Astellas, and Ironwood

July 23, 2018

Company Drug/Device Medical Condition Status
Blade Therapeutics BLD-2660 debilitating fibrotic diseases Phase I trial initiated
SOM Biotech SOM3355 chorea movements associated with Huntington’s disease Phase II trial initiated enrolling 30 subjects
Concentric Analgesics, Inc. CA-008 post-surgical pain Phase II trial initiated
Ironwood Pharmaceuticals, Inc. linaclotide irritable bowel syndrome with constipation (IBS-C) Phase IIIb trial initiated enrolling 600 adult IBS-C subjects in the U.S.
RDD Pharma RDD-0315 fecal incontinence in subjects with spinal cord injury IND clearance granted by the FDA
MaxCyte MCY-M11 (chimeric antigen receptor (CAR) therapeutic candidate) solid tumors IND clearance granted by the FDA
Stryker Corporation Surpass Streamline Flow Diverter unruptured large and giant wide neck intracranial aneurysms PMA granted by the FDA
Astellas Pharma Inc. and Pfizer Inc. XTANDI (enzalutamide) castration-resistant prostate cancer, including men with non-metastatic CRPC sNDA approval granted by the FDA
Adaptiiv 3D Bolus Software cancer 510(k) clearance granted by the FDA
Zavation Normandy VBR System (Cervical and Thoracolumbar Expandable Corpectomy Cage) cervical spine (C2-C7) and thoracolumbar spine (T1-L5) for partial or total replacement of a diseased, collapsed, damaged or unstable vertebral body 510(k) clearance granted by the FDA
Quidel Corporation Solana Bordetella Complete Molecular Diagnostic Assay detection of Pertussis (whooping cough) Parapertussis Infections 510(k) clearance granted by the FDA
Genentech TECENTRIQ (atezolizumab) in combination with Avastin (bevacizumab) chronic lymphocytic leukemia Breakthrough Therapy Designation granted by the FDA
Gamida Cell NiCord hematopoietic stem cell transplantation (HSCT) Orphan Drug Designation granted by the FDA
Inozyme Pharma INZ-701 ENPP1 Deficiency (GACI in infants and ARHR2 post-infancy) Orphan Drug Designation granted by the FDA
Vallum Corporation polyetheretherketone (PEEK) spinal interbody fusion device spinal fusion Clearance granted by the FDA
SIGA Technologies Inc. and U.S. Department of Health and Human Services’ BARDA TPOXX (tecovirimat) smallpox Approval granted by the FDA
Janssen Pharmaceutical Companies of Johnson & Johnson SYMTUZA darunavir-based single-tablet regimen (STR) for the treatment of human immunodeficiency virus type 1 (HIV-1) in treatment-naïve and certain virologically suppressed adults Approval granted by the FDA
Trial Results

Viking Therapeutics Announces VK5211 Phase II Study Results

July 23, 2018

Viking Therapeutics announced results from the company’s Phase II study of VK5211 in patients recovering from hip fracture. The Phase II clinical trial was a randomized, double-blind, placebo-controlled, parallel group, international study designed to evaluate the efficacy, safety and tolerability of VK5211 in patients recovering from hip fracture surgery. The top-line data from this study showed that the trial successfully achieved its primary efficacy endpoint, demonstrating statistically significant, dose dependent increases in lean body mass and less head, among patients treated with VK5211, as compared to placebo. The study also achieved important secondary endpoints, demonstrating statistically significant improvements in appendicular lean body mass and total lean body mass compared to placebo. Patients receiving VK5211 also demonstrated numerical improvements in certain exploratory assessments of functional performance. VK5211 demonstrated encouraging safety and tolerability, with no drug-related serious adverse events reported in this study.