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New HIV vaccine shows great results in phase 1 trial

The International AIDS Vaccine Initiative (IAVI) and Scripps Research have recently announced the results of an important Phase I clinical trial. The researchers tested a new vaccine approach designed to prevent HIV infections by stimulating the production of rare immune cells. These cells are needed to create the right antibodies to fight HIV.

The trial saw 48 participants divided into a low-dose group or a high-dose group. They received either the vaccine candidate or a placebo in two doses two months apart. Of those who received the vaccine, 97 percent had developed the right immune cells to respond to an HIV infection.

“This study demonstrates proof of principle for a new vaccine concept for HIV, a concept that could be applied to other pathogens, as well,” Dr William Schief, a professor and immunologist at Scripps Research and executive director of vaccine design at IAVI’s Neutralizing Antibody Center (NAC), whose laboratory developed the vaccine, said in a statement. “With our many collaborators on the study team, we showed that vaccines can be designed to stimulate rare immune cells with specific properties, and this targeted stimulation can be very efficient in humans. We believe this approach will be key to making an HIV vaccine and possibly important for making vaccines against other pathogens.”

The results were presented at the International AIDS Society HIV Research for Prevention (HIVR4P) virtual conference in February. The team has been looking to stimulate the body to create broadly neutralizing antibodies or bnABs, specialized blood proteins that can attach themselves to the spikes on the surface of HIV. This is an immune response that can neutralize diverse strains of the virus.

“We and others postulated many years ago that in order to induce bnAbs, you must start the process by triggering the right B cells — cells that have special properties giving them potential to develop into bnAb-secreting cells,” Schief explained. “In this trial, the targeted cells were only about one in a million of all naïve B cells. To get the right antibody response, we first need to prime the right B cells. The data from this trial affirms the ability of the vaccine immunogen to do this.”

Source: IAVI.org

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HCC risk reduced by aspirin in chronic viral hepatitis

HCC is the fourth-leading cause of cancer mortality worldwide, and is driven mostly by viral hepatitis B (HBV) and viral hepatitis C (HCV) infection. The risk of hepatocellular carcinoma (HCC) was reduced by 31% compared with no aspirin use, and liver-related mortality dropped by 27%, as long as aspirin use continued. The analysis showed that in aspirin users, the 10-year cumulative incidence of HCC was 4% compared with 8.3% in nonusers. After multivariable adjustment, aspirin users had a risk of HCC that was 31% lower compared with nonusers (adjusted subhazard ratio, 0.69; 95% confidence interval.

Source: New England Journal of Medicine

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Chronic adverse events likely common after Anti-PD-1 therapy for Melanoma

Chronic immune-related adverse events (irAEs) associated with anti-programmed cell death-1 (PD-1) therapy for melanoma were more common than previously thought in a retrospective multicenter study.

As reported in JAMA Oncology, Dr. Johnson and colleagues analyzed data on 387 melanoma patients treated at eight academic medical centers between 2015-2020. The median age was 63, 61% were men, and all received adjuvant anti-PD-1 for stage III-IV melanomas.

Sixty-nine percent of patients had any acute irAE, defined as arising during anti-PD-1 treatment, including 19.5% with grades 3-5 events. One patient had neurotoxicity and one had fatal myocarditis.

Chronic irAEs – those that persisted beyond 12 weeks after anti-PD-1 discontinuation – developed in 43.2% of patients; most (96.4%) were grade 1 or 2 and only 14% had resolved by the last available follow-up.

Source: Medscape

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Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer

When esophageal or gastroesophageal-junction cancer remains a threat after chemoradiotherapy and surgery because of residual pathological disease, treatment with the checkpoint inhibitor nivolumab doubles disease-free survival, according to the results of the large international CheckMate 577 trial.

The treatment, also used for kidney, liver, lung and a host of other cancers, is designed to block the cancer’s defense mechanism against the immune system. It costs about $165,000, sells under the brand name Opdivo.

Source: The New England Journal of Medicine

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BRCA1 & BRCA 2 mutations raise risk for Endometrial Cancer also

Women with a BRCA1 or BRCA2 mutation have an increased risk for endometrial cancer (EC), and the greatest risk is for the rare subgroup of serous-like and p53-abnormal endometrial cancers in BRCA1 mutation carriers, according to a Dutch study.

BRCA1 and BRCA2 mutation carriers had a significant two- to three-fold increase in EC risk, with the highest risk increases found for two EC subgroups with “unfavorable” clinical outcomes: serous-like histology (8-10 fold) and p53-abnormal EC (11-12 fold), the researchers report in the Journal of the National Cancer Institute.

Source: Journal of the National Cancer Institute.

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Quadruple medical therapy for Heart Failure

Quadruple therapy with an angiotensin receptor–neprilsyin inhibitor (ARNI), evidence-based β-blocker, mineralocorticoid receptor antagonist (MRA), and sodium glucose cotransporter 2 inhibitor (SGLT2i) may reduce risk of death by 73% over 2 years in patients with heart failure (HF) with reduced ejection fraction (HFrEF).

Simultaneous or Rapid Sequence Initiation of Comprehensive Disease-Modifying Medical Therapy (CDMMT) for Heart Failure:

Source: JAMA

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Higher calorie refeeding effective in teens with anorexia nervosa

Researchers examined data on adolescents (mean age 16.4 years) hospitalized with anorexia nervosa who were randomized to higher-calorie refeeding (n=60) or lower-calorie refeeding (n=51). Patients started higher-calorie refeeding (2,000 kcals/day, increasing by 200 kcals per day) or lower-calorie refeeding (1,400 kcals/day, increasing by 200 kcals every other day) within 24 hours of admission.

The primary endpoints were clinical remission at one year, defined by reaching a weight of at least 95% of median body mass index (BMI) based on U.S. Centers for Disease Control and Prevention growth charts, and psychological recovery, defined by achieving a global score within one standard deviation of community norms on the Eating Disorder Examination Questionnaire (EDE-Q).

Source: Reuters

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European Union approved Duvelisib for CLL and Follicular Lymphoma

European Union approval has been recommended for duvelisib (Copiktra) for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or refractory follicular lymphoma (FL) who have received at least two prior lines of therapy.

Duvelisib is an inhibitor of phosphoinositide 3–kinase (PI3K) and is the first drug to act as a dual inhibitor of PI3K-delta and PI3K-gamma. These enzymes are involved in the proliferation and survival of malignant B-cell lines and primary CLL tumor cells and are involved in immunologic pathways in the tumor microenvironment of malignant B cells.

Duvelisib is already on the market in the United States; it was approved in 2018 for the same two indications and also for use in the treatment of small lymphocytic lymphoma (CLL/SLL).

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FDA approves neuromodulation device to improve gait in MS

The US FDA has approved the Portable Neuromodulation Stimulator for the short-term treatment of walking impairments as a result of mild to moderate symptoms from multiple sclerosis (MS).

PoNS is a prescription-only device intended to be used in combination with a supervised therapeutic exercise program in patients aged 22 years and older with MS.

PoNS is a neuromuscular tongue stimulator that generates electrical pulses that stimulate the trigeminal and facial nerves, sending neural impulses to the brain stem, which is thought to enhance neuroplasticity to address motor deficits.

The device’s controller and mouthpiece are connected to each other by a cord. The mouthpiece is held in place by the lips and teeth and the control unit is worn around the neck during a patient’s visit with a therapist.

In a randomized, controlled, double-blind trial involving 20 patients with MS-related gait deficits, 10 patients used the PoNS device and 10 used a sham control device that did not deliver stimulation.

No serious safety adverse events were reported in clinical studies or separate real-world data provided by the company, the FDA said.

The PoNS device should not be used by patients with penetrating brain injuries, neurodegenerative diseases, oral health problems, chronic infectious diseases, unmanaged hypertension or diabetes, pacemakers, and/or a history of seizures.

Source: FDA

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FDA approves Transcatheter Pulmonary Valve for Congenital Heart Disease

The US FDA has approved Medtronic’s Harmony Transcatheter Pulmonary Valve (TPV) System to treat severe pulmonary regurgitation in pediatric and adult patients who have a native or surgically repaired right ventricular outflow tract (RVOT).

The Harmony TPV is the first nonsurgical heart valve to treat severe pulmonary valve regurgitation, which is common in patients with congenital heart disease.

The Harmony valve, which was granted breakthrough device designation, is a 22 mm or 25 mm porcine pericardium valve, sewn to a nitinol frame. It is implanted with a 25-French delivery system using a coil-loading catheter.

The FDA approval was based on the 70-patient prospective, nonrandomized, multicenter Harmony TPV Clinical study, in which 100% of patients achieved the primary safety endpoint of no procedure or device-related deaths 30 days after implantation.

Among 65 patients with evaluable echocardiographic data, 89.2% met the primary effectiveness endpoint of no additional surgical or interventional device-related procedures and acceptable heart blood flow at 6 months.

Adverse events included irregular or abnormal heart rhythms in 23.9% of patients, including 14.1% ventricular tachycardia; leakage around the valve in 8.5%, including 1.4% major leakage; minor bleeding in 7.0%, narrowing of the pulmonary valve in 4.2%, and movement of the implant in 4.2%.

The Harmony TPV device is contraindicated for patients with an infection in the heart or elsewhere, for patients who cannot tolerate blood thinning medicines, and for those with a sensitivity to nitinol (titanium or nickel).

Source: FDA