Trends & Technology 2023

An experimental vaccine against Marburg virus (MARV) developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), was found to be safe and induced an immune response in a small, first-in-human clinical trial. This phase 1 study tested an experimental MARV vaccine candidate known as cAd3-Marburg. This vaccine uses a modified chimpanzee adenovirus called cAd3, which can no longer replicate or infect cells, and displays a glycoprotein found on the surface of MARV to induce immune responses against the virus. MARV causes a rapidly progressive febrile illness that leads to shock and death in a large proportion of infected individuals. The symptoms of MARV disease are akin to those seen with Ebola virus and can include fever, headache, chills, rash, abdominal pain, vomiting, and diarrhea. As the disease progresses, patients may suffer from multiple organ dysfunction, delirium, and significant bleeding from the gastrointestinal tract or other sites that may result in death. No approved vaccines or specific therapies are available for MARV disease. Forty healthy adult volunteers received a single dose of either a low dose of the vaccine or a higher dose. Volunteers were monitored for adverse reactions to the investigational vaccine and evaluated at regular intervals for 48 weeks to track their immune responses. The trial’s results showed no serious adverse events, and the experimental vaccine was well-tolerated. 95% of participants in the trial exhibited a robust antibody response after vaccination, and 70% maintained that response for more than 48 weeks.

Researchers are seeking to identify the mechanisms behind the tau proteins related to progressive neurodegenerative disorders, including Alzheimer’s disease, to develop treatments. Previous efforts to detect biomarkers in blood have been hampered by the protective blood-brain barrier. Scientists found that using focused ultrasound-mediated liquid biopsy in a mouse model released more tau proteins and another biomarker into the blood than without the intervention. The noninvasive method, known as sonobiopsy, uses focused ultrasound to target a precise location in the brain. Once located, the researchers inject microbubbles into the blood that travel to the ultrasound-targeted tissue and pulsate, which safely opens the blood-brain barrier. The temporary openings allow biomarkers – such as tau proteins and neurofilament light chain protein (NfL), both indicative of neurodegenerative disorders – to pass through the blood-brain barrier and release into the blood. This method could facilitate diagnosis of neurodegenerative disorders. Sonobiopsy significantly enhanced the release of pTau proteins and a secondary marker of neurodegeneration into the bloodstream for noninvasive diagnosis of neurodegenerative diseases. The team will next examine the qualitative effects of sonobiopsy on plasma biomarkers, characterize the effects of focused ultrasound parameters, and determine an optimal blood collection time, as well as how sonobiopsy can be applied to release larger brain-derived protein biomarkers.

Researchers at the National Institute on Drug Abuse (NIDA) and the Centers for Disease Control and Prevention (CDC) found that the proportion of opioid overdose deaths involving buprenorphine, a medication used to treat opioid use disorder, did not increase in the months after prescribing flexibilities were put in place during the COVID-19 pandemic. In 2021, nearly 107,000 people died of a drug overdose, with 75% of those deaths involving an opioid. Though the benefits of providing medication for opioid use disorder are well-known, only 22% of people with opioid use disorder receive medications. Buprenorphine, one of these medications, helps reduce opioid misuse, decreases risk for injection-related infectious diseases, and decreases risk for fatal and nonfatal overdoses. The recently signed Fiscal Year 2023 omnibus appropriations bill amended the Controlled Substances Act to eliminate the requirement that clinicians obtain a specific waiver to prescribe buprenorphine to treat opioid use disorder, but buprenorphine remains a Schedule III controlled substance with restrictions on prescribing. During the onset of the COVID-19 pandemic, the United States government implemented prescribing flexibilities to facilitate buprenorphine access for patients with opioid use disorder. These updated policies allowed clinicians to remotely prescribe buprenorphine to new patients without conducting in-person examinations, expanded payment for telehealth services, and provided flexibility on accepted communication technologies. Researchers found that buprenorphine was involved in a very small proportion of drug overdose deaths between July 2019 and June 2021 – only 2.2% of the 89,111 total overdose deaths and 2.6% of the 74,474 opioid-involved overdose deaths. Between April 2020 and June 2021, when buprenorphine prescribing regulations were relaxed in response to the COVID-19 pandemic, the researchers found that the proportion of those deaths involving buprenorphine did not increase.

Transforming vaccine structures could increase the efficacy of cancer vaccines

Researchers have found a new way to significantly increase the potency of vaccines using chemistry and nanotechnology to change the structural location of adjuvants and antigens on and within a nanoscale vaccine. This finding exemplifies that vaccine structure is a critical factor in determining efficacy. With most conventional vaccines, the antigen and the adjuvant are blended and injected into a patient. There is no control over the vaccine structure and limited control over the trafficking and processing of the vaccine components. Spherical nucleic acids (SNAs) allow scientists to pinpoint exactly how many antigens and adjuvants are being delivered to cells. SNAs also enable scientists to tailor how these vaccine components are presented and the rate at which they are processed. The heightened emphasis on structure has the potential to improve the effectiveness of conventional cancer vaccines, which historically have not worked well. The team has now studied the effect of vaccine structure in the context of seven different types of cancer to determine the most effective architecture to treat each disease. The study showed that attaching two different antigens to an SNA comprising a shell of adjuvant was the most potent approach for a cancer vaccine structure. It led to a 30% increase in antigen-specific T-cell activation and doubled the number of proliferating T cells, compared to a structure in which the same two antigens were attached to two separate SNAs.

BRIUMVI™ anti-CD20 monoclonal antibody approved for treatment of relapsing forms of multiple sclerosis

TG Therapeutics, Inc. announced the commercial launch of BRIUMVI™ for the treatment of relapsing forms of multiple sclerosis (RMS) to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. BRIUMVI is a novel monoclonal antibody that targets a unique epitope on CD20-expressing B-cells. BRIUMVI is uniquely designed to lack certain sugar molecules normally expressed on the antibody. Removal of these sugar molecules, a process called glycoengineering, allows for efficient B-cell depletion at low doses. BRIUMVI was granted approval by the U.S. Food and Drug Administration (FDA) based on data from the ULTIMATE I & II Phase 3 trials, which demonstrated superiority over teriflunomide in significantly reducing the annualized relapse rate (ARR), the number of T1 Gd-enhancing lesions, and the number of new or enlarging T2 lesions. ULTIMATE I & II were randomized, double-blind, active comparator-controlled clinical trials of identical design in over 1,000 patients with RMS treated for 96 weeks. Both studies enrolled patients who had experienced at least one relapse in the previous year, two relapses in the previous two years, or had the presence of a T1 gadolinium (Gd)-enhancing lesion in the previous year. Patients were randomized to receive either BRIUMVI, given as an I.V. infusion with gradually increasing doses over the weeks of the trial, as well as an oral placebo administered daily, or teriflunomide, the active comparator, given orally as a 14 mg daily dose with I.V. placebo administered on the same schedule as BRIUMVI. BRIUMVI is the first and only anti-CD20 monoclonal antibody approved for patients with RMS that can be administered in a one-hour infusion following the starting dose. The launch of BRIUMVI includes an extensive program designed to support patients through their treatment journey.

Technology

The FDA has given clearance to Lightning Flash, the most advanced mechanical thrombectomy system on the market. Penumbra Inc.’s Lightning Flash is designed to quickly remove large blood clots in the body, including venous thrombus and pulmonary emboli, with catheter engineering and dual clot detection algorithms. The torqueable, larger catheter is designed to remove a large clot burden in the pulmonary arteries or deep venous system more efficiently while maintaining safety profile with computer-aided algorithms that can distinguish flowing blood from clot. The Lightning Flash catheter is made with MaxID hypotube technology, allowing an inner diameter similar to large-bore catheters while maintaining a lower profile and a soft, atraumatic tip designed to help navigate the complex and delicate anatomy of the body. When used together, the device is intended to help remove blood clots quickly while minimizing potential blood loss. Lightning products are the only computer-aided mechanical thrombectomy systems currently available in the U.S., and early data has shown improvement in clinical outcomes and quality of life.

Cook Medical launches portfolio of urological bipolar electrodes

Cook Medical has launched a new portfolio of urological bipolar electrodes in the U.S. This portfolio includes the products that urologists use most frequently to focus on daily electrode needs when performing procedures on the bladder and prostate. The bipolar electrodes portfolio includes a total of seven products. Six of the products are configurations indicated for use in transurethral resection, ablation, and soft tissue removal of the prostate and bladder and where hemostasis is required, including a bipolar transurethral bladder loop, four transurethral cutting loops, and a bipolar transurethral needle electrode. The seventh product, the Bipolar Transurethral Plasma Disc^®, is made for electro-vaporization in urological procedures to help with vaporization of the prostate and coagulation. The patented concentric, multitiered disc design provides concentrated current density to be more energy efficient while still supporting current flow and plasma ignition. The distal wires of each electrode tip are made from a platinum-iridium alloy, which extends from the leading edge past the stabilizer. The platinum-iridium alloy is reinforced by being crimped deep into the body of the electrode for durability. The electrodes have a shelf life of five years, providing additional stock and supply benefits.

CEYEBER develops smart intraocular lens technologies to address macular degeneration and prevent blindness

The CEYEBER Third Eye™ is the next leap in smart intraocular lens technologies. The CEYEBER Third Eye™ is an intraocular lens and a solution for macular degeneration and preventing blindness. This has the potential to significantly reduce the prevalence of global blindness and visual impairment. Age-related macular degeneration affects nearly 200 million people worldwide. In cases of macular degeneration, optical signals cannot reach the brain as they should. By placing CEYEBER’s high-resolution, finely pixelated display in the eye, doctors may be able to help those with significant degeneration regain a crucial amount of sight. Developed by health care company Strathspey Crown, the product features smart-lens technology that includes an implantable intraocular lens with an optic, a camera and an LED display, and a communications module that wirelessly transmits and receives information.