Iscalimab

Pictured: Sanofi sign in front of building/iStock, JHVEPhoto Wednesday, Sanofi released data from a Phase II study showing its investigational anti-CD40L antibody frexalimab met the trial's primary endpoint and significantly lowered disease activity in patients with relapsing multiple sclerosis. After 12 weeks, patients treated with high and low doses of frexalimab saw an 89% and 79% reduction in the number of new gadolinium-enhancing (GdE) T1-lesions, respectively, compared with the placebo. At the 24-week follow-up, 96% of patients in the higher dose group did not show signs of new GdE T1-lesions. Both frexalimab doses also decreased total GdE T1-lesions and new or enlarging T2-lesions. As for safety, Sanofi found frexalimab to be generally well-tolerated. Sanofi will present these findings during a late-breaking session at the 2023 Consortium of Multiple Sclerosis Centers annual meeting. The company will also push frexalimab into a pivotal trial in MS, which is expected to begin in 2024. Frexalimab is an investigational monoclonal antibody that works by blocking the costimulatory CD40/CD40L pathway, which under healthy circumstances, is crucial for the activation and function of the adaptive and innate immune response. By inhibiting this pathway, frexalimab could address the underlying hyperactive autoimmune pathology of MS. Sanofi’s candidate belongs to a class of medications that is promising in theory but has historically been held back by safety concerns. In the late 1990s, Biogen kicked off several clinical trials of its anti-CD40L antibody ruplizumab and a competing antibody, toralizumab, developed by Idec Pharmaceuticals. Both were eventually discontinued due to thromboembolic side effects. More recently, Novartis has also encountered difficulties with its CD40L blocker iscalimab. In September 2021, the investigational antibody failed to prove its superiority to tacrolimus at preventing organ rejection in kidney transplant recipients. The company was forced to terminate this trial. A year later, in October 2022, Novartis axed another iscalimab trial in liver transplantation after the antibody had a worse benefit/risk pro tacrolimus in these patients. Sanofi Rallies in MS Wednesday’s data drop comes nearly a year after the FDA put Sanofi’s other lead MS candidate, tolebrutinib, under partial clinical hold. The regulatory order was triggered by documented cases of drug-induced liver injury in trial participants who had been treated with the candidate. According to Sanofi, patients who developed these liver injuries had underlying conditions that predisposed them to the complication, and discontinuing treatment would normalize liver injury biomarker levels. Tolebrutinib is in a class of drugs that inhibit the BTK enzyme, an essential component in the B-cell development pathway. Targeting BTK could dampen the excessive activation of B-cells, which play a role in autoimmune diseases such as MS and myasthenia gravis. In February 2023, after having its development suspended for months, Sanofi discontinued the development of tolebrutinib for myasthenia gravis. The drug remains under the FDA’s pause for MS. Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com

Latest patient-level data analysis by Spherix Global Insights showcases year over year shifts in nephrology and rheumatology practice patterns alongside strong appetite for new LN pipeline drugs. EXTON, Pa., Jan. 20, 2023 /PRNewswire/ -- With the approvals of GlaxoSmithKline's Benlysta (belimumab) in lupus nephritis (LN) at the end of 2020 and Aurinia's Lupkynis (voclosporin) at the beginning of 2021, practitioners now have valuable new treatment options to battle this complex and serious condition. Spherix Global Insights has been a leader in tracking the lupus nephritis market for several years, covering physician perspectives, treatment patterns, and pipeline assessments. Spherix's second annual RealWorld Dynamix™ Lupus Nephritis (US) patient chart audit – released in December 2022 – uncovers differences in specialists' perceptions and real-world treatment patterns and outcomes among 962 LN patients with Class III or IV (+/- V) and Class V of the disease; 138 US rheumatologists and 104 US nephrologists collaborated on the project. Compared to the prior year (n=954 patients), use of Aurinia's novel calcineurin inhibitor expanded significantly, regardless of which specialty was managing the treatment regimen. Use of Benlysta was relatively flat with rheumatology-managed patients being far more likely to be treated with the agent than nephrology-managed patients. Among patients not treated with Lupkynis, physicians identified 14% as being likely to initiate the drug within the next twelve months; this is down from 22% in 2021. LN patients under nephrology management were three times as likely to be on an SGLT2 inhibitor compared to those under management of a rheumatologist. By contrast, rheumatology patients were twice as likely to be on a biologic-based regimen and more likely to be on branded Lupkynis than generic CNIs compared to nephrology patients. Unsurprisingly, rheumatology-managed patients had higher mean eGFR levels compared to those being managed by nephrologists. With these new FDA-approved options available, use of "off label" rituximab saw major erosion over the past year. For Roche, which is advancing Gazyva (obinutuzumab) in LN, this pattern may erode the bridge that most physicians see between rituximab and Gazyva, given their similar mechanisms of action. Overall, the majority of LN patients are still treated with steroids with a relatively high percent on doses of more than 5mg, which is generally where practitioners become concerned about safety. With steroid minimization increasingly a key goal in LN patient management to avoid the serious side effects of the drug class, it is notable that both Benlysta and Lupkynis succeed in achieving this result in a sizable proportion of patients. Of note, Benlysta had a better overall steroid-sparing result than Lupkynis with one-third of patients able to fully discontinue steroids altogether since starting on the drug. Most audited LN patients displayed extra-renal manifestations of lupus, most commonly skin involvement, in addition to other comorbidities like hypertension and anemia. Notably, B-cell targeted therapies Benlysta and rituximab are more commonly chosen for patients with moderate-to-severe skin issues versus Lupkynis, which tends to be known more for its perceived quicker onset of action and effect on proteinuria. With 40-50% of LN patients still not "optimally managed," there is ample opportunity for agents in the very robust pipeline including AstraZeneca's Saphnelo (anifrolumab), Roche-Genentech's Gazyva (obinutuzumab), Janssen's Tremfya (guselkumab), Horizon's daxdilimab (HZN-7734), Novartis' Cosentyx (secukinumab), iscalimab, and ianalumab (VAY736), and Vera Therapeutic's atacicept, all of which are evaluated on familiarity, level of interest, and potential patient candidacy in the research. Saphnelo (anifrolumab) and Gazyva (obinutuzumab) stand out as the two agents that are most appealing to practitioners, with rheumatologists more bullish on Saphnelo overall. Up to 30% of LN patients in the audit are considered strong candidates for AZ's Saphnelo, with rheumatologists seeing more potential upside. Among rituximab-treated patients, 39% are considered strong candidates for Gazyva. Additional differences in pipeline agent preference and the "whys" behind those perceptions are highlighted in the published research. Insights from the report also reveal which clinical trial endpoints physicians find most important in their clinical practice. About RealWorld Dynamix™ RealWorld Dynamix™ is an independent, data-driven service unveiling real patient management patterns through rigorous analysis of large-scale patient chart audits. Insights reveal the "why" behind treatment decisions, include year over year trending to quantify key aspects of market evolution, and integrate specialists' attitudinal & demographic data to highlight differences between stated and actual treatment patterns. About Spherix Global Insights Spherix Global Insights is a leading provider of market research, business intelligence and advisory services to the global life sciences industry. The company's unique service offerings are powered by deep therapeutic knowledge, the Spherix Network specialty physician panel, and commercially relevant analyses to enable strategic decision-making by our valued customers. A trusted advisor and industry thought leader, Spherix Global Insights provides specialized market expertise in six (6) focused therapeutic areas including: dermatology, gastroenterology, nephrology, neurology, rheumatology and ophthalmology. To learn more about Spherix Global Insights, visit spherixglobalinsights.com or connect through LinkedIn and Twitter. All company, brand or product names in this document are trademarks of their respective holders. Spherix Global Insights Contacts: Ryan Rex, Rheumatology Insights Director [email protected] Scott Upham, Corporate Communications [email protected] SOURCE Spherix Global Insights