Junlin Healthcare New Drug Express – Issue 3, 2020: Highlights on TCR-T Therapy Breakthroughs, Risankizumab Superiority in Psoriasis, and mRNA Vaccine Progress

This week, there were 8 new drug data entries, including 4 for oncology, 1 for infectious diseases, 2 for metabolic disorders, and 1 for dermatology.

Moderna Announces Positive Interim Results for Safety and Immunogenicity at 7 Months from Phase 1 Clinical Study of Its Investigational CMV Vaccine

Moderna Announces Positive Interim Results for Safety and Immunogenicity at Seven Months Following the Third Dose of Its Investigational Cytomegalovirus Vaccine (mRNA-1647) in Phase 1 Clinical Study

mRNA-1476 is a CMV vaccine composed of six mRNA components, five of which encode different subunits of the CMV cell membrane-associated pentameric complex, and one of which encodes glycoprotein B (gB).

In the Phase I trial, the second interim analysis reported on the safety and immunogenicity for the first three dose levels up to seven months after the start of the clinical trial, as well as for the highest dose level (300 µg) up to three months.

In both the CMV seronegative and seropositive groups, neutralizing antibody titers against epithelial cell infection increased significantly. MRNA-1647 is expected to be the first mRNA vaccine globally to enter Phase 2 clinical trials for CMV.

Schematic of mRNA-1476 

Data source: Moderna

Sintilimab Met Primary Endpoint in Phase 3 Study as First-Line Treatment Combined with Chemotherapy for NSCLC Without EGFR Sensitizing Mutations or ALK Gene Rearrangements

Innovent Announces That Sintilimab Met Primary Endpoint in Interim Analysis of Phase 3 Study as First-Line Treatment for NSCLC Without EGFR Sensitizing Mutations or ALK Gene Rearrangements, in Combination with Pemetrexed Disodium and Platinum-Based Chemotherapy

Sintilimab is a PD-1 antibody.

In the ORIENT-11 study, a Phase 3, randomized, double-blind, controlled trial, 397 patients were enrolled. The primary endpoint was progression-free survival (PFS) assessed according to RECIST criteria, and secondary endpoints included overall survival (OS), safety, and others.

Interim analysis met the primary endpoint; detailed data will be disclosed later.

The U.S. FDA Has Approved a New Indication for Semaglutide Injection to Reduce the Risk of Major Adverse Cardiovascular Events in Patients with Type 2 Diabetes and Cardiovascular Disease

Novo Nordisk Announces U.S. FDA Approval of New Indication for Semaglutide Injection 0.5 mg or 1 mg to Reduce the Risk of Major Adverse Cardiovascular Events (MACE) in Adults with Type 2 Diabetes and Known Cardiovascular Disease

Semaglutide is a glucagon-like peptide-1 (GLP-1) analog, a hormone that induces insulin secretion.

In the SUSTAIN 6 cardiovascular outcomes trial, Ozempic or placebo was added to standard care in adults with type 2 diabetes and established cardiovascular disease, with final assessment of cardiovascular safety.

Ozempic significantly reduced the risk of the composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke.

Intercept Pharmaceuticals Announces FDA Delays Decision Date on Potential First NASH Drug Obeticholic Acid (OCA)

Intercept Pharmaceuticals issued an announcement stating that the U.S. FDA has delayed the review decision date for obeticholic acid (OCA), its potential first-in-class new drug for NASH.

Obeticholic acid is a selective farnesoid X receptor (FXR) agonist.

Phase 3 Trial: Comparing the Therapeutic Efficacy of Different Doses of Obeticholic Acid versus Placebo

At 18 months of treatment, among the intention-to-treat (ITT) population receiving different doses of OCA, the proportion of patients who achieved an improvement in liver fibrosis by more than one stage without worsening of NASH was 17.6% (10 mg) and 23.1% (25 mg), compared with 11.9% in the placebo group. This is currently the only investigational NASH therapy to have yielded positive results in late-stage clinical trials.

FDA Accepts BMS’s BLA for Approval of Opdivo and Yervoy Combination Therapy as First-Line Treatment for NSCLC Without EGFR or ALK Mutations

The FDA has accepted the BLA submission from BMS, approving the combination therapy of Opdivo and Yervoy for first-line treatment of patients with metastatic or recurrent non-small cell lung cancer without EGFR or ALK genomic tumor aberrations.

Opdivo is a PD-1 antibody, and Yervoy is a CTLA-4 antibody; both are products of BMS.

In the Phase 3 CheckMate-227 trial, the study comprised two parts: a) comparing Opdivo in combination with low-dose Yervoy versus chemotherapy in patients whose tumors did not express PD-L1; b) comparing Opdivo in combination with low-dose Yervoy versus chemotherapy in patients regardless of PD-L1 expression status.

Among patients with PD-L1 ≥1% and those with PD-L1 <1% treated with the Opdivo plus low-dose Yervoy combination regimen, the 2-year survival rate was 40% in both groups. In contrast, among patients in the chemotherapy control group, the 2-year survival rates were 33% for those with PD-L1 ≥1% and 23% for those with PD-L1 <1%.

Astellas Publishes Research Findings on Oncolytic Viruses Expressing IL-7 and IL-12 Enhancing Sensitivity to Immune Checkpoint Antibody Therapies

Astellas Publishes Research in Science Translational Medicine on Oncolytic Viruses Expressing IL-7 and IL-12 to Enhance Sensitivity to Immune Checkpoint Antibody Therapies

As an oncolytic virus, ASP9801 can disrupt the integrity of tumor tissue and release tumor antigens. The IL-7 and IL-12 expressed by ASP9801 can significantly promote T cell proliferation and activation.

In animal experiments, comparing the immune cell proliferation and anti-tumor activity of unmodified oncolytic viruses with those engineered to express IL-7 and IL-12

Oncolytic viruses engineered to express IL-7 and IL-12 demonstrated enhanced immune cell proliferation and significantly improved antitumor activity in animal studies. Furthermore, pretreatment with oncolytic viruses expressing IL-7/IL-12 substantially potentiated the therapeutic efficacy of PD-1 and CTLA-4 antibodies.

Mechanism of Action of ASP9801

Data source: Astellas

AbbVie Announces That Its IL-23 Antibody Risankizumab Demonstrated Superior Clinical Efficacy to Secukinumab in Head-to-Head Trial for the Treatment of Adult Psoriasis

AbbVie Announces That Its IL-23 Antibody Risankizumab Demonstrated Superior Clinical Efficacy Compared with Secukinumab (an IL-17A Inhibitor) in a Head-to-Head Trial for the Treatment of Adults with Moderate-to-Severe Plaque Psoriasis

Risankizumab is a humanized IgG1 monoclonal antibody targeting IL-23A, which selectively binds to the p19 subunit of IL-23 and inhibits the interaction between IL-23 and its receptor. In terms of signal transduction, Risankizumab and secukinumab (which targets IL-17A) are in an upstream-downstream relationship.

Phase 3 trial, head-to-head, enrolling 327 patients, with approximately 1:1 randomization

After 52 weeks of treatment, the proportion of patients receiving risankizumab who achieved PASI 90 (a 90% improvement in the Psoriasis Area and Severity Index) was as high as 87%, compared with 57% for secukinumab. The results at 16 weeks also demonstrated non-inferiority

Adaptimmune Announces Initial Responses in Four Solid Tumor Indications with Its SPEAR T-Cell Technology Platform, Including Two Confirmed Responses

Adaptimmune Announces Preliminary Responses in Four Solid Tumor Indications Using Its SPEAR T-Cell Technology Platform: Including Two Confirmed Responses and Two Pending Confirmation. On This News, Adaptimmune’s Pre-Market Stock Price Surged 200%.

Apaptimmune’s SPEAR T-cell technology is a TCR-T therapy.

Phase I Trial, Single-Arm Last-Line Therapy

Two confirmed responses included: one case of hepatocellular carcinoma (100% reduction in lesion size; the first patient enrolled in the Phase 1 ADP-A2AFP trial) and one case of rectal mucosal melanoma (42% reduction in lesion size; the first patient enrolled in the Phase 1 ADP-A2M429L trial).