AstraZeneca’s Forxiga treatment has received approval from the EU to extend the cover to heart failure (HF) with reduced ejection fraction (HFrEF).

Consequently, it will now include patients across the full spectrum of left ventricular ejection fraction (LVEF), including HF with mildly reduced and preserved ejection fraction (HFmrEF, HFpEF).

The latest European Commission green light arrives after an initial positive opinion of the Committee for Medicinal Products for Human Use in December 2022. This had been based on positive results from the DELIVER phase 3 clinical trial.

Meanwhile, results from the research emerging from both the DELIVER and DAPA-HF phase 3 trials also confirmed Forxiga as the first HF therapy to establish mortality benefits across the full ejection fraction range.

Mene Pangalos, executive vice president BioPharmaceuticals R&D at AstraZeneca, was confident that the latest approval would yield positive results for patients: “This broader indication for Forxiga for the treatment of symptomatic chronic heart failure across the full ejection fraction range will help more patients to benefit from this well-tolerated and guideline-directed treatment.

“We are redefining treatment of cardiorenal diseases with Forxiga’s demonstration of life-saving benefits, underscoring AstraZeneca’s commitment to provide innovative solutions that can help address the complexities of heart failure across the spectrum of the disease.”

HF is a chronic, long-term condition that becomes more serious over time and typically affects about 15 million people across Europe. Approximately half of HF patients die within five years of diagnosis, while patients with HFmrEF and HFpEF are at greater risk of death and hospitalisations. HFmrEF and HFpEF are also majorly under diagnosed as symptoms are often masked by other clinical conditions.

Forxiga – also known as Farxiga in the US – is approved for the treatment of patients with type 2 diabetes, HFrEF and CKD in more than 100 countries around the world including the US, EU, China and Japan. It has most recently received regulatory approvals in Britain, Japan and Turkey.

Small Pharma – a company focused on psychedelic-assisted therapies for mental health conditions – has confirmed that a first subject has been dosed in its phase 1 study evaluating SPL028.

The treatment is a deuterated N, N-dimethyltryptamine (DMT) candidate, providing supportive therapy among healthy volunteers. The trial represents the first-in-human study investigating the overall profile of SPL028.

The phase 1 study is a blinded, placebo-controlled, randomised and dose-escalating study being conducted at MAC Clinical Research in Manchester, England. It is designed to evaluate tolerability, safety, pharmacodynamics and pharmacokinetics of both intravenous and intramuscular delivery of SPL028.

Preclinical research from Small Pharma indicated that SPL028 offered a similar safety and pharmacological profile to its lead candidate, SPL026, while being differentiated by its pharmacokinetics.

Now the company aims to deliver a treatment with an extended psychedelic experience when compared to 20 to 25 minutes with SPL026, but still significantly shorter than the experience of other psychedelics, such as lysergic acid diethylamide and psilocybin.

During the SPL028 clinical programme, Small Pharma is exploring whether an extended duration could offer a treatment tailored for other mental health conditions in addition to depression. Meanwhile, the pharmacokinetic profile of SPL028 offers the chance to investigate additional routes of administration – potentially expanding patient convenience.

George Tziras, chief executive officer at Small Pharma, explained: “This is a significant milestone for Small Pharma, with our second key programme now in clinical development. The recent announcement on 25 January 2023 of our positive phase 2a results demonstrates proof of concept for SPL026 in treating major depression.”

Dr Carol Routledge, chief medical and scientific officer at Small Pharma, concluded: “With the SPL028 trial now underway, we look forward to learning more about its pharmacokinetic and pharmacodynamic properties in humans. Comparison of the IM and IV routes of administration in this study aims to create options for patients and physicians, which may help to expand convenience and accessibility.”

Valneva – a company specialising in vaccines – has completed enrolment for a phase 3 trial of its single-shot chikungunya vaccine candidate, VLA1553. The group is comprised of adolescents and initial results of the study are expected halfway through this year.

Conducted in partnership with Instituto Butantan, VLA1553-321 is a multi-centre, double-blinded, randomised and placebo-controlled phase 3 trial. In total, 754 adolescents aged 12 to 17 years were vaccinated following randomisation at a 2:1 ratio to receive either VLA1553 or the placebo.

The central target of the trial is to evaluate immunogenicity and safety 28 days after a single vaccination with VLA1553. Participants will then be evaluated for the primary endpoint and monitored for up to 12 months.

The company completed submission of the Biologics License Application (BLA) to the US Food and Drug Administration for approval of VLA1553 in individuals of 18 years and above in December 2022. If approved it could become the first chikungunya vaccine to be marketed in the US.

Valneva reported final pivotal phase 3 data for VLA1553 in March last year and final results in May. Furthermore, the company also recently reported positive antibody persistence data with a 99% seroresponse rate 12 months after the single-dose vaccination.

The research is funded by the Coalition for Epidemic Preparedness Innovations (CEPI) and aims to support the label extension in this age group following the initial regulatory approval.

Ultimately, the adolescent trial is expected to yield licences for the vaccine in Europe and Brazil, which would be the first potential approval for use in endemic populations.

Ipsen has revealed follow-up results from its phase 3 CheckMate-9ER trial. The study demonstrated that Cabometyx in combination with nivolumab provides survival benefits after three-years of treating advanced renal cell carcinoma (RCC), compared to sunitinib.

During the CheckMate-9ER trial, overall survival benefits were maintained during three-years of follow-up. Meanwhile, median overall survival was significantly higher for patients on Cabometyx (also known as cabozantinib) together with nivolumab versus sunitinib.

Accounting for around 90% of cases, RCC is the most common type of kidney cancer. When detected at an early stage, the five-year survival rate is high, but for people living with advanced or late-stage metastatic RCC the survival rate is considerably lower – around 12%.

The study results were also assessed by the following International Metastatic Renal Cell Carcinoma Database Consortium risk scores. Benefits were duly identified with Cabometyx in combination with nivolumab across all efficacy measures, regardless of IMDC risk.

Steven Hildemann, executive vice president at Ipsen, explained: “The results from the CheckMate-9ER study continue to demonstrate sustained, now three-year long-term benefits for people living with advanced renal cell carcinoma across the most meaningful efficacy measures and risk scores, adding to the body of evidence we have for Cabometyx plus nivolumab. We sincerely thank the patients who participated in the trial, their families and their healthcare teams.”

Mauricio Burotto, medical director at Bradford Hill Clinical Research Center, added: “Despite the progress made through science and medicine, there remains a need for treatment options that can durably extend survival for patients with metastatic renal cell carcinoma, especially for those classified as higher risk.”