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NEFEGAN demonstrated clinically meaningful results over placebo. Credit: Peakstock via Shutterstock. Everest Medicines has received approval from the Singapore Health Sciences Authority (HSA) for NEFEGAN to treat primary immunoglobulin A nephropathy (IgAN) in adults at disease progression risk. An oral, delayed-release budesonide formulation, NEFEGAN is also known as Nefecon in other regions and is the first medication for IgAN, having received the first full approval from the US Food and Drug Administration. Singapore is the third region within Everest’s territories to approve the new drug application (NDA), following mainland China and Macao. The efficacy and safety of Nefecon were evaluated in the Phase III NefIgArd clinical trial. This randomised, double-blind, multicentre study tested a once-a-day dose of 16mg Nefecon against a placebo in adults with primary IgAN who were also receiving optimised angiotensin system inhibitors therapy. See Also: Johnson & Johnson’s paediatric HIV-1 treatment secures FDA approval FDA approves Boehringer’s SPEVIGO for psoriasis treatment Spanning over two years, the NefIgArd trial included nine months of treatment with either Nefecon or a placebo, succeeded by a follow-up period of 15 months without the study drug. The time-weighted average of the estimated glomerular filtration rate (eGFR) over two years was the trial’s primary endpoint. The findings showed that Nefecon offered a statistically significant and clinically meaningful benefit over a placebo. Additionally, the trial demonstrated a favourable two-year total eGFR slope difference of 2.95ml per minute and 1.73m² per year with Nefecon treatment. These benefits were consistent across the entire study population, irrespective of the baseline level of urine protein-creatinine ratio. An in-depth analysis of the full two-year results from the NefIgArd trial, which involved 364 patients, was conducted to examine the response to Nefecon treatment based on self-reported ancestry. Among the participants, 83 identified as Asian and 275 as White. In both subgroups, Nefecon’s 16mg a day dosage over nine months led to a clinically meaningful preservation of kidney function, with a reduction in proteinuria and stabilisation of eGFR compared to placebo. Everest CEO Rogers Yongqing Luo said: “The NDA approval in Singapore marks an important event for IgAN patients in the region as we continue to expand patient access to Nefecon throughout Asia, an area of high IgAN disease prevalence. “Following approval of Nefecon in mainland China and commercial launch in Macao, we are working to rapidly expand availability of this first-in-disease therapy which targets the origin of the disease and can slow disease progression to more underserved patients in 2024, including Hong Kong, Taiwan and South Korea.”

Cardiometabolic disease isn’t a big part of Roche’s drug portfolio or pipeline, but the pharmaceutical giant is trying to change that with a deal to share in the development of an experimental Alnylam Pharmaceuticals hypertension drug that could offer patients efficacy and dosing advantages. According to deal terms announced Monday, Roche is paying $310 million for outside-of-the-U.S. rights to the drug, zilebesiran. The companies will share in the development of the RNA therapy for hypertension. Roche has the opportunity to lead future development of the drug for other indications. Cambridge, Massachusetts-based Alnylam is a pioneer among companies developing therapies that leverage RNA interference, a pathway in cells that stops protein translation. Sometimes referred to as “gene silencing,” this approach employs small pieces of RNA to stop the production of a disease-causing protein. Zilebesiran is intended to block production of angiotensinogen in the liver. This protein is upstream in a protein cascade that plays a role in blood pressure regulation. Hypertension drugs that address angiotensin are already available as small molecules dosed as once-daily pills. Zilebesiran a small interfering RNA molecule formulated as an injection that lasts up to six months. Alnylam has advanced zilebesiran to Phase 2 testing. The Roche deal follows publication of Phase 1 data last week in the New England Journal of Medicine. Results of the dose-ascending study showed dose-dependent decreases in levels of angiotensin in the blood. The drug also resulted in lowering of blood pressure that was sustained for up to 24 weeks. No serious adverse events were reported and the most common side effect was mild injection-site reactions. There are already many hypertension drugs available for the more than 1.2 billion adults who have hypertension. However, many patients are unable to adequately manage their high blood pressure with those medications, putting them at higher risk of developing more cardiovascular problems. Two Phase 2 tests of zilebesiran are enrolling patients whose hypertension is inadequately controlled by standard of care drugs. One study will evaluate the drug as a monotherapy; preliminary data are expected later this year. A second Phase 2 trial will test the drug in combination with standard hypertension medications. Preliminary data are expected in early 2024. The size of the hypertension market and the fact that so many patients are inadequately served by currently available medications makes the indication attractive for drug research efforts. Mineralys Therapeutics is developing a small molecule that takes a different approach than other oral hypertension drugs. In February, the Radnor, Pennsylvania-based biotech raised $192 million in IPO cash to continue clinical testing of this hypertension drug, lorundrostat. AstraZeneca joined the pursuit for new hypertension drugs with a $1.3 billion acquisition CinCor Pharma early this year. The CinCor drug, baxdrostat, is also a once-daily oral small molecule. Alnylam won the first ever RNAi drug approval in 2018 for Onpattro, a drug that treats nerve pain caused by the rare disease hereditary transthyretin amyloidosis. While Alnylam has since won additional approvals in rare diseases, bringing RNAi to more prevalent conditions is a key part of the drugmaker’s growth strategy. Under Alnylam’s deal with Roche, the biotech will continue to lead development of zilebesiran for the first indication. Funding of the program will be split 40% to Alnylam and 60% to Roche. Regulatory and commercial milestones payments could bring Alnylam’s total payout to up to $2.8 billion. According to deal terms, Alnylam will share equally in the profits and losses from sales of the drug in the U.S. The biotech will receive royalties from Roche’s sales of the drug in all other markets. “With this collaboration, we now can develop zilebesiran in a more robust way, allowing us to have cardiovascular outcomes data in hand at launch to ensure results relevant not only for health authorities but also for access and clinical practice in order to ultimately reach as many patients as possible,” Alnylam CEO Yvonne Greenstreet said in a prepared statement.

– IONIS-FB-L Rx achieved a 44% mean reduction in proteinuria in patients treated for 6 months – Roche to advance IONIS-FB-L Rx into Phase 3 development in H1 2023 CARLSBAD, CA, USA I November 7, 2022 I Ionis Pharmaceuticals, Inc. (Nasdaq: IONS ) today presented positive results from a Phase 2 clinical study of IONIS-FB-L Rx in patients with immunoglobulin A nephropathy (IgAN). Results from the study were presented in a poster session at the American Society of Nephrology's (ASN) Kidney Week 2022. In the Phase 2 study, IONIS-FB-L Rx met its primary endpoint of change in 24-hour urinary protein, demonstrating a 44% mean reduction in proteinuria from baseline to week 29. Kidney function, as measured by estimated glomerular filtration rate (eGFR), was maintained in all patients in the study. IONIS-FB-L Rx achieved robust and sustained reductions in plasma complement Factor B (CFB), Alternative Pathway Activity (AH50), and urinary complement fragment Ba (Factor Ba). IONIS-FB-L Rx also demonstrated a favorable safety and tolerability profile in this study. "We are extremely pleased with the results from this proof-of-concept Phase 2 study of IONIS-FB-L Rx , which demonstrated the potential to treat IgAN by inhibiting complement Factor B," said Richard Geary, Ph.D., executive vice president, drug development, at Ionis. "IgAN can lead to chronic kidney disease and kidney failure and has few treatment options. Given the significant unmet medical need, we are particularly pleased that Roche is moving expeditiously to advance IONIS-FB-L Rx into Phase 3 development for IgAN in the first half of next year." About the IONIS-FB-L Rx Study IONIS-FB-L Rx is being evaluated in an ongoing open-label, single arm, Phase 2 clinical study in up to 25 participants with IgAN in two dose cohorts treated sequentially ( NCT04014335 ). The first dose cohort included 10 patients treated for 29 weeks. The primary endpoint in the study is the change in 24-hour urine protein excretion from baseline to week 29. The study is also evaluating reduction in plasma complement Factor B, measures of kidney function and safety and tolerability of monthly dosing of IONIS-FB-L Rx . About IgA Nephropathy (IgAN) Immunoglobulin A nephropathy (IgAN) is an important cause of chronic kidney disease and renal failure. Also known as Berger's disease, IgAN is characterized by deposition of IgA and Complement 3 (C3) activation products in the glomerular mesangium of the kidneys, resulting in inflammation and tissue damage. Although IgAN may occur at any age, it generally presents in the second or third decade of life. The clinical presentation, disease progression and histologic findings are highly variable among affected individuals. Current therapies are aimed at reduction of protein levels in the urine with administration of angiotensin inhibitors and control of blood pressure. Sometimes immunosuppressive therapies are given; however, this practice is not universally accepted. About Ionis Pharmaceuticals, Inc. For more than 30 years, Ionis has been the leader in RNA-targeted therapy, pioneering new markets and changing standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a premier late-stage pipeline highlighted by industry-leading cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision of becoming a leading, fully integrated biotechnology company. To learn more about Ionis, visit www.ionispharma.com and follow us on Twitter @ionispharma. SOURCE: Ionis Pharmaceuticals