COVID-19 News: Vaccine 101, Vaccine Advisory Committee meeting, BARICITINIB (+ Remdesivir) for treatment, LUCIRA at-home test kit, CASIRIVIMAB + IMDEVIMAB for treatment, Bioburden reduction systems, Non-invasive remote monitoring devices

Vaccine Development – 101

Center for Biologics Evaluation and Research (CBER) ensures rigorous scientific and regulatory processes and review.

Typical process
It Starts in a Lab

Research Moves Forward

Testing the Vaccine in People

Special Considerations – Public health emergencies and more information

Assessment of Manufacturing is Also a Key Component

Seeking Approval

Prescribing Information/Labeling

FDA Oversight Continues After Approval

FDA Research Provides a Unique Perspective

NEW WEBSITE

Dec 10, Advisory Committee Meeting to Discuss COVID-19 Vaccine Candidate

Vaccines and Related Biological Products Advisory Committee (VRBPAC) to discuss EUA of COVID-19 vaccine from Pfizer, Inc. in partnership with BioNTech Manufacturing GmbH

  • Public Meeting with outside scientific and public health experts from around the country
  •  Discussion about safety and effectiveness of vaccine
  • Help ensure clear public understanding of the scientific data and information that the FDA will evaluate in order to make a decision about whether to authorize a vaccine for emergency use for the prevention of COVID-19.”

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BARICITINIB (+ REMDESIVIR )

Eli Lilly ( and Gilead)

INDICATION: Treatment of suspected or laboratory confirmed COVID-19 in hospitalized adults and pediatric patients two years of age or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

ADDRESSING UNMET NEED: New treatment for COVID

MECHANISM OF ACTION: Janus kinase inhibitor (JAK) which blocks enzymes interfering with the pathway that leads to inflammation

EFFECTVENESS an SAFETY:

  • Based on totality of evidence
  • Randomized, double-blind, placebo-controlled clinical trial conducted by National Institute of Allergy and Infectious Diseases (NIAID), n=1,0333 with moderate-severe COVID-19, baricitinib + remdesivir vs placebo + remdesivir, followup for 29 days
  • Primary Endpoint: Recovery defined as either being discharged from hospital or being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care; 7 days for baricitinib + remdesivir vs. 8 days for placebo + remdesivir.
  • Odds of patient’s condition progressing to death or being ventilated at day 29 was lower in the baricitinib + remdesivir group vs placebo + remdesivir group (statistically significant)
  • Similarly, odds of clinical improvement at day 15 was higher in the baricitinib + remdesivir group (statistically significant)

REGULATORY PATHWAY: Emergency Use Authorization

  • Previously approved for treatment of moderately to severely active rheumatoid arthritis
  • Expedited by Coronavirus Treatment Acceleration Program (CTAP)

Fact Sheet

LUCIRA COVID-19 All-In-One Test Kit 

Lucira Health

INDICATION FOR USE: Single-use test kit intended to detect SARS-CoV-2 that causes COVID-19. This test is authorized for prescription home use with self-collected nasal swab samples in individuals aged 14 and older who are suspected of COVID-19 by their healthcare provider.

Test is authorized for use at the Point of Care (POC), in patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation

Test utilizes a molecular amplification technology for the detection of SARS-CoV-2 RNA in individuals with known or suspected COVID-19. Positive results are indicative of the presence of SARS-CoV-2. Individuals who test positive should self-isolate and seek additional care from their healthcare provider.

Negative results do not preclude SARS-CoV-2 infection. Individuals who test negative and continue to experience COVID-like symptoms should seek follow up care from their healthcare provider.

PERFORMANCE CHARACTERISTICS:

  • Analytical sensitivity based on Limit of detection, Inclusivity, Cross-reactivity,
  • Human usability study, n=398 asymptomatic subjects, for safe and effective use
  • Community testing study, n=101 asymtomatic subjects, independent collection of Lucira nasal swab samples and running the test. Comparable results vs high sensitivity molecular FDA Authorized SARS-CoV-2 assay (Roche Cobas)

ADDRESSING UNMET NEED: First COVID-19 diagnostic test for self-testing at home and that provides rapid results

REG PATHWAY: Emergency Use Authorization

Instructions for Use

CASIRIVIMAB + IMDEVIMAB intravenous infusion 

Regeneron

INDICATION: Treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization. This includes those who are 65 years of age or older or who have certain chronic medical conditions.

ADDRESSING UNMET NEED: Pandemic treatment option that may help outpatients avoid hospitalization and alleviate the burden on health care system

MECHANISM OF ACTION: Monoclonal antibodies that are specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment and entry into human cells

EFFICACY & SAFETY:

  • Randomized, double-blind, placebo-controlled clinical trial, n= 799 non-hospitalized adults with mild to moderate COVID-19 symptoms
  • Primary endpoint: Time-weighted average change in viral load from baseline; viral load reduction in patients treated with casirivimab and imdevimab was larger than placebo
  • Secondary endpoint: Hospitalizations and emergency room visits within 28 days after treatment; 3% of casirivimab and imdevimab-treated patients vs. 9% on placebo
  • Possible side effects: Anaphylaxis and infusion-related reactions, fever, chills, hives, itching and flushing. 

REGULATORY PATHWAY: Emergency Use Authorization

  • Part of Coronavirus Treatment Acceleration Program

FACT SHEET

Bioburden Reduction Systems

Bioburden: Whole population of viable microorganisms that inhabit a non-sterile surface or device

 Reduction : Dry heat, such as application of temperatures of 70° C for 60 minutes or 75° C for 30 minutes, will kill many of the moderately-resistant microbes present

Intention: To kill and reduce microorganisms on a non-sterile device surface. For use in addition to existing CDC reuse recommendations

Use: In shortage situations, when there is an insufficient supply of essential supplies such as new respirators

GUIDANCE

Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring During the pandemic

Policy to expand availability and capability of non-invasive remote monitoring devices

  • To facilitate patient monitoring while reducing patient and healthcare provider contact
  • To remain in effect only for the duration of the COVID-19 public health emergency
  • Enforcement policy applies to legally marketed non-invasive remote monitoring devices that measure or detect common physiological parameters to support patient monitoring
  • Devices can be connected to wireless network to transmit patient’s measurements directly to health care provider

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Image credit: FDA, Lucira Health, Regeneron

COVID-19 News: BAMLANIVIMAB monoclonal antibody therapy, cPass neutralization antibody detection kit, Enhancing clinical trial diversity, Policy for diagnostic tests, Coronavirus Treatment Acceleration Program, Fraudulent flu products

bamlanivimab investigational monoclonal antibody therapy

Eli Lilly

INDICATION: For patients with positive results of direct SARS-CoV-2 viral testing who are 12 years of age and older weighing at least 40 kilograms, and who are at high risk for progressing to severe COVID-19 and/or hospitalization

ADDRESSING UNMET NEED: Monoclonal antibody for coronavirus treatment

MECHANISM OF ACTION: Monoclonal antibody that is specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment and entry into human cells

EFFECTIVENESS & SAFETY:

  • Interim analysis from Phase II randomized, double-blind, placebo-controlled clinical trial, n=465 non-hospitalized adults with mild to moderate COVID-19 symptoms; several doses of bamlanivimab vs placebo
  • Primary endpoint: Change in viral load from baseline to day 11; similar outcomes
  • Secondary endpoint: COVID-19-related hospitalizations or emergency room visits within 28 days after treatment; 3% for bamlanivimab vs.10% for placebo

REGULATORY PATHWAY; EUA, Coronavirus Treatment Acceleration Program

Fact Sheet

cPass SARS-CoV-2 Neutralization Antibody Detection Kit

GenScript

INDICATION: Qualitative detection of total neutralizing antibodies to SARSCoV-2 in human serum and K2-EDTA plasma. Intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection

Emergency use of this test is limited to authorized laboratories

ADDRESSING UNMET NEED: First serology test authorized to detect neutralizing antibodies from recent or prior COVID-19 infection

ASSAY PRINCIPLE: Blocking Enzyme-Linked Immunosorbent Assay (ELISA) intended for qualitative direct detection of total neutralizing antibodies to SARS-CoV-2 in human serum and K2-EDTA plasma

Instruction For Use

FDA Guidance: Enhancing the Diversity of Clinical Trial Populations

Clinical trials design of drugs and biologics to include different demographic characteristics (e.g., sex, race, ethnicity, age) and non-demographic characteristics (e.g., patients with organ dysfunction, comorbid conditions, and disabilities)

  • Addresses health disparities
  • Critical during the COVID-19 public health emergency as certain segments of the population are being affected by the virus in different ways
  • Developers of CVOID-19 treatments or vaccines for COVID-19 should include diverse populations to understand their risks or benefits across all groups

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FDA Guidance: Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised)

To help rapidly expand testing capacity by facilitating development and use of SARS-CoV-2 tests during the public health emergency

  • Two policies for accelerating the development of certain laboratory developed diagnostic tests for COVID-19
  • EUA submission to FDA
  • No EUA submission when test is developed under State authorities and the State takes responsibility

Guidance

Coronavirus Treatment Acceleration Program (CTAP) update

Special emergency program for possible coronavirus therapies

  • Accelerate patient availability of new treatments while maintaining statutory standrads for safety and effectiveness
  • Accelerate development and publication of guidances and other information for industry on developing COVID-19-related treatments

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Fraudulent Flu Products

Unproven products that claim to prevent, mitigate, treat, or cure the flu

  • Not been FDA approved for safety and effectiveness; can be ineffective and dangerous
  • Might cause people to delay, forgo, or stop the medical treatment they need, leading to serious and life-threatening harm
  • Ingredients could lead to unexpected side effects and interactions with other medications
  • Can be found online, including popular marketplaces, and in retail stores
  • Labeled as dietary supplements, foods, hand sanitizers, nasal sprays, or devices

READ Warning Letters page Fraudulent product views


Image credit: FDA, GenScript

Market Authorizations: NIGHWARE App for PTSD sleep disturbance, INMAZEB for Ebola treatment, REACTIV8 Implantable Neurostimulation System for pain, MAKENA withdrawal proposal

NIGHTWARE Digital Therapeutic

Nghtware Inc

INDICATION FOR USE:  Temporary reduction of sleep disturbance related to nightmares in adults 22 years or older who suffer from nightmare disorder or have nightmares from post-traumatic stress disorder (PTSD)

The device should be used in conjunction with prescribed medications for PTSD and other recommended therapies for PTSD-associated nightmares and nightmare disorder

ADDRESSING UNMET NEED: New, low-risk treatment option that uses digital technology to provide temporary relief from sleep disturbance related to nightmares in PTSD patients

DESCRIPTION: Digital therapeutic software using Apple Watch and Apple iPhone

  • Throughout the night, Apple Watch sensors monitor body movement and heart rate during sleep
  • Data are sent to the Nightware server and, using a proprietary algorithm, the device creates a unique sleep profile for the patient
  • When Nightware detects patient experiencing a nightmare based on analysis of heart rate and body movement, the device provides vibrations through the Apple Watch

EFFECTIVENESS AND SAFETY:

  • Randomized, sham-controlled trial of 70 patients for 30 days
  • Patients in the sham group wore the device, but no vibratory stimulation was provided
  • Effectiveness was assessed by Sleep based on two versions of the Pittsburgh Sleep Quality Index scale, including a version intended for PTSD patients
  • Safety was assessed using validated measurements of suicidality and sleepiness
  • Both the sham and active groups showed improvement on the sleep scales, with the active group showing greater improvement than sham
  • Nightware is intended to be used under the supervision of a healthcare provider. Patients who have been known to “act out” during their nightmares (sleepwalking, violence) should not use Nightware

REGULATORY PATHWAY: De Novo pathway with Breakthrough Designation

INMAZEB™ (atoltivimab, maftivimab, and odesivimab-ebgn) injection

Regeneron Pharmaceuticals

INDICATION: Treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection

ADDRESSING UNMET NEED: First FDA-approved treatment for Zaire ebolavirus infection in adult and pediatric patients.

MECHANISM OF ACTION:  Targets the glycoprotein on the surface of Ebola virus and blocks attachment and entry of the virus.

EFFICACY:

  • Clinical trial led by the U.S. National Institutes of Health and the Democratic Republic of the Congo (DRC) Institut National de Recherche Biomédicale
  • Multi-center, open-label, randomized controlled trial, n= 382 adult and pediatric patients with confirmed Zaire ebolavirus infection during an Ebola virus outbreak in 2018-2019 in DRC, Inmazeb (50 mg of each monoclonal antibody) vs control
  • Primary efficacy endpoint: 28-day mortality
  • With Inmazeb, 33.8% died after 28 days vs. 51% on control

SAFETY:

  • Most common: fever, chills, tachycardia (fast heart rate), tachypnea (fast breathing), and vomiting; however, these are also common symptoms of Ebola
  • Avoid concurrent administration of a live vaccine due to the treatment’s potential to reduce the vaccine’s efficacy.

REGULATORY PATHWAY: BLA

  • Orphan Drug designation,  Breakthrough Therapy designation 

Label

REACTIV8 Implantable Neurostimulation System 

Mainstay Medical

INDICATON FOR USE: For bilateral stimulation of the L2 medial branch of the dorsal ramus as it crosses the L3 transverse process as an aid in the management of intractable chronic low back pain associated with multifidus muscle dysfunction, as evidenced by imaging or physiological testing in adults who have failed therapy including pain medications and physical therapy and are not candidates for spine surgery.

ADDRESSING UNMET NEED: Treatment option for patients who have failed therapy including pain medications and physical therapy and are not candidates for spine surgery 

DEVICE DESCRIPTION: The system consists of an Implantable Pulse Generator (IPG), Leads, surgical tools and accessories, Application Software, Programmer Wand, Activator, Magnet and Tunneler. The ReActiv8 IPG, Torque Wrench and Leads, and the Mainstay Tunneler have been sterilized using ethylene oxide (EO) gas.

EFFECTIVENESS & SAFETY:

  • International, multi-center, prospective, randomized, blinded trial; ReActiv8 System (Treatment group) vs. active Sham Control, n= 204
  • Although the primary efficacy endpoint was not met at the 120-day visit, totality of evidence supports clinical benefit
  • Additional potential secondary benefits were observed, with improvement in patient pain symptoms, as seen in the percent pain relief, and improvement in functionality measured by the Oswestry Disability Index
  • System was determined to have safe electrical and mechanical characteristics
  • Reasonable expectation of biocompatibility
  • Adverse events that were reported were consistent with those reported with the marketed spinal systems

REGULATORY PATHWAYL PMA

  • Device Generic Name: Stimulator, neuromuscular, lower back muscles, totally implanted for pain relief
  • Device Procode: QLK

Label

MAKENA (hydroxyprogesterone caproate injection) proposed withdrawal

FDA has issued a notice of opportunity for a hearing (NOOH) for withdrawal of MAKENA, marketed by Amag Pharmaceuticals  

  • Accelerated approval granted to Amag Pharmaceuticals in 2011 to reduce the risk of preterm birth in women who previously had a spontaneous (unexplained) preterm birth
  • Company required to conduct a clinical trial to confirm the drug provided clinical benefit to newborns
  • However, confirmatory study failed to substantiate efficacy
  • Health Care Professionals discuss Makena’s benefits, risks and uncertainties with their patients to decide whether to use while a final decision is being made

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Image credits: Nightware, Regeneron, Mainstay, Amag