JunLian Healthcare Global New Drug Insights Weekly – Issue 19 (August 19–25, 2019)
Aug 26, 2019 10:17
CST Updated
10:17
Legend Capital
Early-stage venture capital and growth-stage private equity investment institutions
August 19–25, 2019: A total of 10 new drug data entries were recorded this week, including 4 in oncology, 3 in anti-infectives, and 1 each in cardiovascular disease, gene therapy, and dermatology.
❖The National Healthcare Security Administration has released the conventional list portion of the 2019 National Reimbursement Drug List (NRDL), marking the long-awaited implementation of NRDL adjustments. The previous NRDL was published in 2017, and before that, in the distant year of 2009, indicating an accelerating trend in the iteration and evolution of the list. Furthermore, a significant feature of this adjustment is the removal of certain adjuvant drugs, such as deproteinized calf blood extract and mouse nerve growth factor. These so-called “miracle drugs” were once capable of sustaining entire listed companies on their own. With each version comes its own stars; with the announcement of the new list, the golden age of adjuvant drugs is coming to an end. Subsequently, the National Healthcare Security Administration will conduct a series of negotiation-based access procedures for innovative drugs, and some blockbuster medications are expected to emerge as fortunate beneficiaries.
❖AstraZeneca announced that its SGLT2 inhibitor, Farxiga, met the primary endpoint in a Phase III clinical trial for heart failure. This marks the first time an SGLT2 inhibitor has demonstrated efficacy in heart failure within a prospective trial. Previously, due to their straightforward glucose-lowering mechanism, SGLT2 inhibitors were often regarded as second-line agents in the management of diabetes mellitus (DM). Consequently, AstraZeneca, Eli Lilly, and Johnson & Johnson have been seeking additional evidence of clinical benefit. Eli Lilly’s Jardiance became the first glucose-lowering drug to demonstrate cardiovascular benefits, thereby surging ahead to become the industry leader. Given the substantial unmet medical need in heart failure and the absence of new therapies over the past two decades, Farxiga’s unexpected success may reshape the competitive landscape of the SGLT2 inhibitor market.
GSK’s BCMA-Targeting Antibody-Drug Conjugate for the Treatment of Patients with Relapsed/Refractory Multiple Myeloma
achieved positive results in its pivotal Phase 2 clinical trial
GSK’s BCMA-targeting antibody-drug conjugate, belantamab mafodotin, achieved positive results in a pivotal Phase 2 clinical trial in patients with relapsed/refractory multiple myeloma (R/R MM) who had received multiple prior therapies.
Belantamab mafodotin is a conjugate of a humanized anti-BCMA antibody and a cytotoxic agent, which specifically delivers the cytotoxic agent into multiple myeloma (MM) cells by targeting BCMA, thereby exerting a cancer cell-killing effect.
Phase 2, Randomized, Open-Label Trial with 196 Patients with Relapsed/Refractory Multiple Myeloma (R/R MM)
Data analysis indicates that belantamab mafodotin achieves an overall response rate (ORR) of 60%, a complete response rate of 15%, and a progression-free survival (PFS) of 12 months.
BCMA Has Become a Testing Ground for Numerous Therapies
Data source: ResearchGate
Mustang Bio’s MB-107 (Gene Therapy) for the Treatment of X-Linked Severe Combined Immunodeficiency
Granted Regenerative Medicine Advanced Therapy (RMAT) Designation by the U.S. FDA
Mustang Bio’s MB-107 lentiviral vector gene therapy for the treatment of X-linked severe combined immunodeficiency (X-SCID) has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the U.S. FDA
MB-107 is an innovative gene therapy that uses a lentiviral vector to introduce a healthy IL2RG gene into hematopoietic stem cells obtained from the patient ex vivo. These genetically engineered hematopoietic stem cells are then infused back into the patient.
Phase 1/2 Clinical Trial: Gene Therapy Administered to 8 Infants with X-SCID
Not only did the patients regain NK cell and B cell function, but four infants also discontinued intravenous immunoglobulin therapy for immune support. Among these four infants, three developed antibody responses to vaccines, further confirming their functional B cell activity.
The U.S. FDA has accepted Astellas’ supplemental new drug application for Xtandi,
Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Astellas and Pfizer Announce U.S. FDA Acceptance of Supplemental New Drug Application (sNDA) for Xtandi (enzalutamide) for the Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Xtandi is a selective androgen receptor inhibitor that not only blocks the binding of androgens to their receptors but also inhibits nuclear translocation of the receptor and prevents the binding of the androgen receptor to DNA.
In a randomized, double-blind, phase 3 clinical trial, 1,150 patients with metastatic hormone-sensitive prostate cancer (mHSPC) received treatment with Xtandi or placebo. Patients concurrently underwent androgen deprivation therapy (ADT).
Compared with placebo plus ADT, the treatment group reduced the risk of radiographic progression or death by 61% (HR=0.39, 95% CI: 0.30-0.50, p<0.001).
ViiV Healthcare Announces Its Long-Acting Innovative Two-Drug Combination Therapy for HIV,
Met the Primary Endpoint in Phase 3 Clinical Trials
ViiV Healthcare Announces That Its Long-Acting Innovative Two-Drug HIV Regimen Met the Primary Endpoint in the Phase 3 ATLAS-2M Clinical Trial
In the two-drug combination, rilpivirine is an oral non-nucleoside reverse transcriptase inhibitor (NNRTI) already approved in the United States and the European Union, while cabotegravir is an integrase inhibitor (INI) under development.
In a 48-week, randomized, open-label, active-controlled study, the efficacy of once-every-8-weeks versus once-every-4-weeks injections was compared in 1,045 patients infected with HIV-1.
The overall safety and antiviral activity following injections every 8 weeks were consistent with the results of the every-4-week injection regimen.
The U.S. FDA Accepts BeiGene’s New Drug Application for the BTK Inhibitor Zanubrutinib,
For the treatment of relapsed/refractory mantle cell lymphoma (R/R MCL)
BeiGene Announces FDA Acceptance of New Drug Application for BTK Inhibitor Zanubrutinib for the Treatment of Patients with Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL); FDA Grants Priority Review
Zanubrutinib is a BTK inhibitor.
The program includes one global Phase 1/2 clinical trial in patients with B-cell lymphoma, one multicenter Phase 2 clinical trial conducted in China in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), as well as safety and non-clinical data obtained from five clinical trials involving a total of 641 patients.
In the pivotal Phase 2 trial in China, the overall response rate (ORR) reached 83.5%, with a complete response (CR) rate of 58.8% and a partial response (PR) rate of 24.7%. In the global Phase 1/2 clinical trial, the ORR was 85.4%, with a CR rate of 29.2% and a PR rate of 56.3%.
Eiger BioPharmaceuticals’ PEGylated Interferon Lambda Receives Breakthrough Therapy Designation,
Treatment of Hepatitis D Virus (HDV) Infection
Eiger BioPharmaceuticals, a company focused on the research and development of targeted therapies for rare diseases, announced that its pegylated interferon lambda has been granted Breakthrough Therapy Designation by the FDA for the treatment of hepatitis D virus (HDV) infection.
Lambda is a “first-in-class” type III interferon (type III IFN) that stimulates immune responses during viral infection to protect the host.
In the phase 2 clinical trial LIMT (Lambda Interferon Mono Therapy), 33 patients with HDV infection received treatment.
After 24 weeks of treatment, the durable virologic response rate in patients reached 36%, which is superior to the historical performance of pegylated IFN-α.
Cassiopea Submits Topical Androgen Receptor Inhibitor to the FDA
New Drug Application for Clascoterone 1% Cream for the Treatment of Acne
Cassiopea, a company focused on developing novel-mechanism dermatological therapies, announced that it has submitted a New Drug Application (NDA) to the FDA for its first-in-class topical androgen receptor inhibitor, 1% clascoterone cream, for the treatment of acne.
Clascoterone is designed to be an effective and safe topical androgen receptor inhibitor for the treatment of acne or androgenetic alopecia, without systemic side effects.
Clascoterone underwent two pivotal Phase 3 clinical trials
At Week 52, 57% and 62% of subjects, respectively, achieved an improvement of at least 2 points on the Investigator’s Global Assessment (IGA) scale, attaining clear (score of 0) or almost clear (score of 1) skin. Furthermore, clascoterone demonstrated a favorable safety and tolerability profile.
AstraZeneca's SGLT2 inhibitor dapagliflozin,
Achieved the primary composite endpoint in the Phase 3 DAPA-HF clinical trial
AstraZeneca announced that its SGLT2 inhibitor dapagliflozin (brand name Farxiga) met the primary composite endpoint in the Phase 3 DAPA-HF clinical trial.
Dapagliflozin is a first-in-class oral SGLT2 inhibitor. It has been approved by the FDA to improve glycemic control in patients with type 2 diabetes, alongside diet and exercise.
In the Phase 3 clinical trial, patients were typical heart failure patients, with or without type 2 diabetes. Patients with heart failure with reduced ejection fraction received either dapagliflozin or placebo in addition to standard therapy.
The primary composite endpoint of the trial was worsening heart failure events (defined as hospitalization or emergency department visits for heart failure) or cardiovascular death. Dapagliflozin met the primary composite endpoint of the trial. Detailed data from this trial will be presented at future medical conferences.
FDA Approves Nabriva Therapeutics’ Innovative Antibiotic Xenleta for Market Launch,
Adult Patients with Community-Acquired Bacterial Pneumonia (CABP)
Nabriva Therapeutics Announces FDA Approval of Its Innovative Antibiotic Xenleta (lefamulin) for the Treatment of Adult Patients with Community-Acquired Bacterial Pneumonia (CABP)
Lefamulin is an innovative pleuromutilin-class antibiotic that inhibits bacterial protein synthesis by binding to the peptidyl transferase center (PTC) of the bacterial ribosome, thereby suppressing bacterial growth.
In two pivotal Phase 3 clinical trials, the safety and efficacy of intravenous and oral lefamulin versus moxifloxacin for the treatment of adult community-acquired bacterial pneumonia (CABP) were evaluated, with a total of 1,289 patients enrolled.
Lefamulin demonstrated non-inferiority in efficacy compared with moxifloxacin.
Camrelizumab for cHL: Key Phase II Data Officially Published, Showing an Objective Response Rate of 76.0%
Hengrui’s PD-1 inhibitor camrelizumab: Phase 2 data in patients with relapsed or refractory classical Hodgkin lymphoma (cHL) officially released, with an objective response rate of 76.0%
Camrelizumab is a PD-1 inhibitor.
In the pivotal Phase II trial, 75 patients with relapsed or refractory classical Hodgkin lymphoma (cHL), with a mean age of 34 years (range: 22–77 years), were enrolled across 14 centers in China and received camrelizumab 200 mg via intravenous infusion every two weeks.
Treatment with camrelizumab was discontinued due to disease progression in 32 patients (42.7%), while the remaining 43 patients continued to receive treatment. The overall response rate (ORR) was 76.0% (57/75), including a complete response rate of 28.0% (21/75) and a partial response rate of 48.0% (36/75).
Phase 2 Results of Camrelizumab
Data Source: Clinical Cancer Research
❖The clinical trial application for the JAK1 inhibitor itacitinib, jointly submitted by Innovent Biologics and Incyte, has been accepted by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration. Currently, no second-generation JAK inhibitors with selectivity for the JAK protein kinase family have been marketed in China.
❖Pharming Group announces collaboration agreement with Novartis, under which Pharming will receive an exclusive license to develop and commercialize CDZ173. CDZ173 is a small-molecule phosphoinositide 3-kinase delta (PI3Kδ) inhibitor developed by Novartis for the treatment of Activated PI3K Delta Syndrome (“APDS”).
❖Amgen and Allergan Announce Positive Top-Line Results from Comparative Efficacy Study of Rituximab Biosimilar ABP798. To date, 23 biosimilars have been approved, with nine targeting Roche’s three blockbuster drugs. Among them, Mvasi and Kanjinti were launched in the U.S. market in mid-July this year, becoming the first biosimilars of Avastin and Herceptin to enter the market.
❖The data manipulation scandal involving Novartis’s SMA gene therapy, Zolgensma, continues to intensify, eroding external confidence in CEO Vas Narasimhan. To date, Novartis has dismissed five scientists implicated in the Zolgensma data manipulation and appointed a new Chief Scientific Officer for AveXis.
❖The National Healthcare Security Administration and the Ministry of Human Resources and Social Security jointly issued the “National Catalogue of Drugs for Basic Medical Insurance, Work-Related Injury Insurance, and Maternity Insurance.” The regularly included portion released this time comprises a total of 2,643 drugs, including 1,322 Western medicines and 1,321 Chinese proprietary medicines (including 93 ethnic medicines). Traditional Chinese medicine decoction pieces are managed under an inclusion-based approach, with 892 items incorporated. Regarding removed items, a total of 150 varieties were delisted, approximately half of which were drugs whose approval numbers had been revoked by the national drug regulatory authorities.