JunLian Healthcare Global New Drug Insights Newsletter – Issue 30

This week, there were 10 new drug data entries: 4 in oncology, 2 in anti-infectives, 1 in hematology, 1 in nephrology, 1 in hepatology, and 1 in metabolic disorders.

NextCure’s Second-Generation Immunotherapy NC318 Announces Phase 1/2 Clinical Data

NextCure Announces Latest Data on Its Novel Immuno-Oncology Drug NC318

NC318 is a monoclonal antibody that targets Siglec-15 (S15), which is expressed on the surface of tumor cells and M2 macrophages. It potently inhibits T-cell activation, thereby suppressing the human immune response against cancer cells.

A total of 43 patients with previously treated advanced solid tumors were enrolled across six dose-escalation cohorts (8–800 mg, administered once every two weeks). Common cancer types included non-small cell lung cancer (NSCLC; n=10), ovarian cancer (n=7), melanoma (n=6), breast cancer (n=3), and colorectal cancer (n=3).

A total of 32 patients were evaluable for efficacy. In NSCLC, one patient achieved a complete response lasting 41 weeks; another achieved a partial response lasting 14 weeks; and three additional patients achieved stable disease. The ORR was 29% (2/7), and the DCR was 71% (5/7).

NC318Approvedsiglec-15Mechanisms for Suppressing Immune Overexpression

Data Source: NextCure

Halozyme’s Hyaluronidase Formulation PEGPH20 Fails in Phase III Clinical Trial for Pancreatic Cancer

U.S. biotechnology company Halozyme announced that its hyaluronidase formulation PEGPH20 failed in the Phase III clinical trial for pancreatic cancer, known as HALO-301

PEGPH20 is a PEGylated human recombinant hyaluronidase protein that degrades hyaluronic acid. The temporary and reversible degradation of this polysaccharide enhances the diffusion and absorption of macromolecules, enabling many drugs originally requiring intravenous infusion to be administered via subcutaneous injection.

Comparison of the Impact of PEGPH20 versus Placebo on Overall Survival as First-Line Therapy for Advanced Pancreatic Cancer against a Background of Gemcitabine and ABRAXANE®

The OS for the two groups was 11.2 and 11.5 months, respectively, missing the trial endpoint.

 Daiichi Sankyo's New Drug for Diabetic NephropathyesaxerenoneDa3Phase Clinical Endpoints

Daiichi Sankyo announced that esaxerenone, its selective mineralocorticoid receptor inhibitor, met both the primary and secondary endpoints in a pivotal Phase 3 trial for the treatment of patients with early-stage diabetic nephropathy.

Esaxerenone (CS-3150) is a nonsteroidal, selective mineralocorticoid receptor (MR) antagonist; MR is a nuclear receptor that plays a role in many cardiovascular and metabolic diseases.

A randomized, double-blind, placebo-controlled Phase 3 clinical trial in which patients with diabetic kidney disease received treatment with an ARB or an ACE inhibitor

Using the urine albumin-to-creatinine ratio (UACR) as the endpoint, esaxerenone increased the patient remission rate by 22.1%, compared with 4% in the placebo group, thereby meeting the primary endpoint of the trial.

Cirius Therapeutics’ New NASH Drug MSDC-0602K Shows Positive Phase 2b Clinical Trial Results

Cirius Therapeutics Announces That MSDC-0602K Significantly Improved Liver Enzyme Levels, Glycemic Control, and Insulin Resistance in Patients with Non-Alcoholic Steatohepatitis (NASH) in the Phase 2b EMMINENCE Trial

MSDC-0602K is a second-generation oral insulin sensitizer that, compared with the first generation, modulates mitochondrial pyruvate carrier (MPC) function while minimizing the direct agonist effects on peroxisome proliferator-activated receptor gamma (PPARγ).

Enrollment of 402 NASH patients for efficacy comparison across different doses

Three different doses of MSDC-0602K (62.3 mg, 125 mg, and 250 mg) significantly reduced the NAFLD Activity Score (NAS) in patients, with 33.3%, 39.8%, and 42.6% of patients, respectively, achieving a reduction of at least 2 points in their NAS scores.

Scynexis’ Oral Antibiotic Ibrexafungerp Meets Primary and Key Secondary Endpoints in Phase 3 Clinical Trial

Scynexis Announces That Its Investigational Oral Antifungal Ibrexafungerp Met Primary and Key Secondary Endpoints in Phase 3 Clinical Trial for Patients with Vulvovaginal Candidiasis (VVC)

Ibrexafungerp (SCY-078) is a novel glucan synthase inhibitor that combines the potent activity of glucan synthase inhibitors with the potential flexibility of both oral and intravenous administration.

Randomized, double-blind, placebo-controlled trial enrolling 376 patients with vulvovaginal candidiasis (VVC) who had a signs and symptoms (S&S) score ≥4 (score range: 0–18).

Compared with the placebo group, 50.5% of patients treated with ibrexafungerp achieved clinical cure after 10 days of treatment, defined as a Signs and Symptoms (S&S) score of 0. This rate was significantly higher than that in the placebo group (p=0.001).

Takeda’s Ninlaro Meets Primary Endpoint in Phase 3 Trial for First-Line Treatment of Multiple Myeloma

Takeda Announces That Its Proteasome Inhibitor Ninlaro (ixazomib) Met the Primary Endpoint in a Phase 3 Trial as First-Line Maintenance Therapy for Adult Patients with Multiple Myeloma (MM) Who Have Not Undergone Stem Cell Transplantation

Ninlaro is the first FDA-approved oral proteasome inhibitor, which selectively binds to the PSMB5 subunit of the proteasome and inhibits its activity.

Randomized, double-blind, placebo-controlled study in newly diagnosed adult patients who had not previously undergone stem cell transplantation; after initial therapy and achievement of partial response, patients received either Ninlaro or placebo.

Compared with the placebo group, patients receiving Ninlaro treatment showed a statistically significant improvement in PFS, meeting the primary endpoint of the trial.

Gilead’s Two New HIV Drugs Demonstrate Long-Term Efficacy

Gilead Announces That Descovy, for Reducing the Risk of HIV Infection in Men and Transgender Women as Pre-Exposure Prophylaxis, and Biktarvy, for Treating Patients with Initial HIV Infection, Have Further Demonstrated Their Long-Term Efficacy and Safety in Extension Studies of Phase 3 Trials

Descovy is a combination formulation containing 200 mg of emtricitabine and 25 mg of tenofovir alafenamide; Biktarvy contains an additional ingredient, bictegravir, which is a novel integrase strand transfer inhibitor (INSTI).

The DISCOVER trial was designed to verify whether Descovy meets the non-inferiority criteria compared with the approved PrEP regimen Truvada; the Biktarvy trial aimed to evaluate its efficacy in suppressing HIV-1 in treatment-naïve adults, compared with DTG/ABC/3TC or DTG plus Descovy, respectively.

The average annual HIV incidence rate was 0.16 per 100 person-years in the Descovy group, compared with 0.30 per 100 person-years in the Truvada group; among patients receiving Biktarvy, 82% achieved an HIV-1 RNA level of <50 copies/mL, meeting the non-inferiority criterion for suppression of viral replication compared with the control group.

Sanofi’s Long-Acting Insulin Meets Phase 3 Clinical Trial Endpoints

Sanofi Announces That Its Long-Acting Insulin Toujeo Gla-300 Met Primary Endpoint in Trial for Children and Adolescents (Aged 6 to 17) with Type 1 Diabetes, Compared with Toujeo Gla-100

Toujeo Gla-300 is a long-acting insulin with an insulin concentration three times that of standard 1 mL insulin (100 units/mL), achieving blood glucose reduction by stimulating peripheral glucose uptake and inhibiting hepatic glucose production.

To verify the efficacy of Toujeo Gla-300 versus Toujeo Gla-100 in reducing HbA1c levels and managing glycemic variability among patients aged 6–17 years with type 1 diabetes and baseline HbA1c levels between 7.5% and 11.0%.

The Toujeo Gla-300 group achieved the primary endpoint of non-inferiority in reducing HbA1c levels, and this group also had relatively lower incidence rates of ketosis and severe hypoglycemia (<54 mg/dL).

Bio-Thera's Adalimumab Injection Receives Marketing Approval

Bio-Thera’s adalimumab injection marketing application (CXSS1800018) has been officially approved by the National Medical Products Administration, with indications identical to those already approved in China for the originator drug Humira.

It is the world’s first fully human TNF-α monoclonal antibody approved for marketing. It specifically binds to soluble human TNF-α and blocks its interaction with the cell surface TNF receptors p55 and p75, thereby effectively inhibiting the pro-inflammatory effects of TNF-α.

Developed and submitted for production approval via the biosimilar pathway, using the originator adalimumab as the reference drug, and supported by comprehensive quality similarity studies, non-clinical similarity studies, and clinical comparative studies.

"demonstrated high similarity to the approved reference drug in terms of quality, safety, and efficacy"

Celgene’s Potential Blockbuster Anemia Therapy Reblozyl Approved by FDA for Market Launch

Reblozyl (luspatercept-aamt), jointly developed by Celgene and Acceleron, has received FDA approval for the treatment of anemia in patients with transfusion-dependent beta thalassemia.

Reblozyl is a soluble fusion protein composed of the Fc domain of IgG1 fused to the extracellular domain of activin receptor IIB. It acts as a ligand trap for TGF-β, preventing the activation of the Smad2/3 signaling pathway by TGF-β, thereby promoting the differentiation and maturation of late-stage erythroid cells.

Patients with β-thalassemia requiring transfusion were randomized in a 2:1 ratio to evaluate the efficacy and safety differences between luspatercept plus best supportive care (BSC) and placebo plus BSC, with the primary endpoint being erythroid response.

21% of patients experienced a >33% reduction in transfusion burden compared with baseline, which was significantly superior to the placebo-treated control group (4.5%, p<0.0001).

ReblozylMechanism of Action

Data Source: ACCELERON