Three Investigational Therapies from Novartis, Everest Medicines, and CARsgen Receive Breakthrough Therapy Designation in China

Text: Shibei

On November 30, the CDE publicized three drugs proposed for breakthrough therapy designation: Novartis’ TQJ230 injection, Calliditas Therapeutics’ Nefecon (budesonide) extended-release capsules, and Shanghai Carsgen Pharmaceuticals’ CT053 fully human anti-BCMA autologous CAR-T cell injection.

CT053 Fully Human Anti-BCMA Autologous CAR-T Cell Injection

CT053, a fully human anti-BCMA autologous CAR-T cell injection, is a Class 1 innovative drug independently developed by Carsgen Therapeutics. It consists of T cells modified with chimeric antigen receptors (CARs) targeting B-cell maturation antigen (BCMA) using fully human antibodies, with the primary indicated indication being relapsed/refractory multiple myeloma.

CT053 Demonstrated Excellent Efficacy in an Exploratory Phase I Clinical Study in China. Among 24 patients with relapsed/refractory multiple myeloma (R/R MM), 19 achieved complete response, yielding a complete response rate of 79.2%. Importantly, no grade 3 or higher cytokine release syndrome (CRS) events were observed.

CT053 was granted Orphan Drug designation by the FDA and Priority Medicines (PRIME) designation by the European Medicines Agency (EMA) for the treatment of multiple myeloma in 2019.

Nefecon Sustained-Release Capsules

Nefecon is a delayed-release capsule developed by Calliditas Therapeutics using TARGIT technology, which releases budesonide exclusively in the Peyer’s patches region of the distal small intestine—the site of origin for IgA nephropathy. TARGIT technology enables the active ingredient to pass through the gastrointestinal tract without being absorbed, releasing the drug in a pulsatile manner only upon reaching the lower part of the small intestine.

On November 9, Calliditas Therapeutics announced that the Phase III clinical trial of Nefecon for the treatment of primary IgA nephropathy had met its primary endpoint. Results from Part A of the study showed that after nine months of treatment, the urine protein-to-creatinine ratio (uPCR) in the Nefecon group decreased by an average of 31% from baseline, compared to only a 5% decrease in the placebo group. The Nefecon group demonstrated a mean 27% greater reduction in uPCR compared to the placebo group.

The trial also met its key secondary endpoint, with eGFR remaining stable in patients treated with Nefecon, whereas it declined by 7% in the placebo group. At 9 months, the absolute decline in eGFR was 0.17 mL/min/1.73 m² in patients treated with Nefecon, compared with 4.04 mL/min/1.73 m² in the placebo group.

As early as 2019, Everest Medicines entered into a collaboration with Calliditas Therapeutics, whereby Everest Medicines (which holds 100% ownership of Yunyi Pharmaceutical) would be responsible for the development and commercialization of Nefecon in the Greater China region.

TQJ230 Injection

TQJ230 injection is a cardiovascular therapy targeting lipoprotein(a) [Lp(a)] that Novartis acquired from Akcea Therapeutics, an Ionis company. It is being developed for patients with cardiovascular disease (CVD) and elevated Lp(a) levels. Novartis will be responsible for the global development and commercialization of TQJ230.

TQJ230 is an antisense drug that utilizes Ionis Pharmaceuticals’ advanced ligand-conjugated antisense (LICA) technology to inhibit the production of apolipoprotein(a), thereby reducing lipoprotein(a) [Lp(a)] levels. Elevated Lp(a) is widely recognized as an independent genetic risk factor for cardiovascular disease (CVD), affecting approximately 20%–30% of the CVD patient population. Lp(a) is a lipoprotein present in the bloodstream; high levels of Lp(a) accumulate in the arteries, progressively narrowing them and restricting blood supply to the heart, brain, kidneys, and legs. This leads to an increased risk of coronary heart disease, atherosclerosis, thrombosis, and stroke.

A prior Phase 2 clinical study of TQJ230 (NCT02160899) yielded positive results. The study enrolled a total of 93 participants, who received either placebo (n=29) or TQJ230 (Group A [n=51] and Group B [n=13]). The results showed that mean Lp(a) levels decreased from baseline by 66.8% in Group A and 71.6% in Group B, representing statistically significant differences compared with the placebo group. These early data have generated considerable optimism regarding the outcomes of the ongoing Phase 3 clinical trials.

Source: PharmCube Info

Original Title: CDE Proposes Breakthrough Therapy Designation: Novartis’s Antisense Lipid-Lowering Therapy, Everest Medicines’ Budesonide Extended-Release Capsules, and Carsgen Biologics’ BCMA CAR-T