June 17–23, 2019: A total of 14 new drug data entries were recorded this week, including 6 for oncology, 2 each for metabolic diseases and rare diseases, and 1 each for liver disease, arthritis, psychiatric disorders, and antibiotics.
❖Merck & Co. shared its strategic plan for Keytruda at an investor conference. Although Keytruda currently has more than ten approved indications, Merck believes that the drug’s development is still in its early stages and has previously been used primarily as a treatment for advanced-stage cancers. In the future, Merck plans to shift its use to earlier stages of treatment, such as neoadjuvant therapy. Currently, there are over 1,000 clinical trials underway for Keytruda, including more than 600 combination therapy trials and over 75 registrational clinical trials, with more than 100 trials focusing on neoadjuvant or adjuvant therapy.
❖Amgen has released the first 5-year overall survival (OS) data for its bispecific antibody Blincyto in patients with acute lymphoblastic leukemia, showing a significantly prolonged median OS of 36.5 months among treated patients. As the first FDA-approved bispecific tumor immunotherapy globally and the inaugural approved drug under Amgen’s BiTE technology platform, the expansion of Blincyto’s indications and the advancement of subsequent studies hold highly positive implications for the entire bispecific antibody field. However, despite the significant improvement in OS, the need for daily intravenous infusion due to its short half-life may remain Blincyto’s Achilles’ heel.
❖ArQule Announces Positive Early Clinical Results for Its Investigational BTK Inhibitor ARQ531 in Patients with Relapsed/Refractory B-Cell Lymphoma. Ibrutinib, the first-generation BTK inhibitor, has become a blockbuster drug with annual sales exceeding $5 billion. However, resistance has emerged in some patients, with the C481S mutation being one of the primary resistance mechanisms. ARQ531 inhibits both wild-type and C481S mutant BTK, positioning it as a potential second-generation BTK inhibitor. In the realm of precision medicine, although the emergence of entirely new targets is unlikely, continuous iteration around specific targets is sufficient to sustain the vitality of this field.
Pharmaceutical R&D Trends
Liraglutide Approved for Expanded IndicationsTreating Pediatric Patients
FDA Announces Expanded Approval of Liraglutide for the Treatment of Type 2 Diabetes in Patients Aged 10 and Older
Liraglutide is a GLP-1 analog.
Inclusion Criteria and Study DesignThis approval was primarily based on the results of clinical trials of liraglutide in adult patients, as well as in placebo-controlled clinical trials in pediatric patients aged 10 years and older.
Trial data showed that the proportion of patients with a reduction in glycated hemoglobin (HbA1c) levels of more than 7% was higher in the liraglutide treatment group than in the placebo group (64% vs. 37%).
Innovative GLP-1 Inhibitors for the Treatment of Hypoglycemia After Bariatric Surgery
Granted Breakthrough Therapy Designation
Eiger Biopharmaceuticals Announces FDA Grants Breakthrough Therapy Designation to Its Investigational Drug Avexitide for the Treatment of Post-Bariatric Hypoglycemia
Avexitide is an innovative GLP-1 receptor antagonist.
Inclusion Criteria and Study Design54 patients received treatment.
Compared with the placebo control group, the treatment group showed significantly improved postprandial blood glucose levels and reduced need for acute therapy.
Daiichi Sankyo's Oral Leukemia DrugApproved for Marketing in Japan
Daiichi Sankyo Announces Approval of Vanflyta (quizartinib), an Oral FLT3 Inhibitor Developed by the Company, for Marketing in Japan to Treat Patients with Relapsed or Refractory Acute Myeloid Leukemia Harboring FLT3-ITD Mutations
Vanflyta is an oral FLT3 inhibitor.
Inclusion Criteria and Study DesignApproval was based on results from the pivotal global Phase 3 QuANTUM-R trial and a Phase 2 clinical trial conducted in Japanese patients.
Compared with salvage chemotherapy, Vanflyta significantly improved patients’ overall survival (6.2 months vs. 4.7 months).
Roche's Tumor-Agnostic Personalized TherapyApproved for Marketing in Japan
Roche’s tumor-agnostic, individually tailored therapy Rozlytrek (entrectinib) has been approved in Japan for the treatment of patients with advanced, recurrent solid tumors harboring NTRK gene fusions.
Rozlytrek is a selective tyrosine kinase inhibitor designed to target NTRK and ROS1 gene fusions.
Inclusion Criteria and Study DesignApproval based on the results of multiple clinical trials, including the pivotal Phase 2 STARTRK-2 trial and the Phase 1 STARTRK-1 and ALKA-372-001 trials.
Trial data showed an ORR of 57.4% and a DOR of 10.4 months.
Amgen's Bispecific Antibody Drug BlincytoSignificantly Prolongs Overall Survival in Leukemia Patients
Amgen Announces Positive 5-Year Long-Term Efficacy Data for Bispecific Antibody Blincyto (blinatumomab) in Patients with Acute Lymphoblastic Leukemia
Blincyto is a bispecific antibody molecule targeting CD19 and CD3, developed using Amgen’s bispecific T-cell engager platform.
Inclusion Criteria and Study DesignIn the Phase 2 clinical trial named BLAST, enrolled patients had received more than three rounds of chemotherapy but still had residual cancer cells.
At a median follow-up of 59.8 months, the median OS was 36.5 months, with 76% of patients achieving minimal residual disease (MRD) negativity after treatment.
Figure: Mechanism of Action of Blincyto
Source: Amgen
Reversible BTK InhibitorsTreatmentInitial Efficacy Observed in Lymphoma Treatment
ArQule Announces Positive Early Clinical Trial Results for Its Investigational BTK Inhibitor ARQ 531 in Patients with Relapsed/Refractory B-Cell Lymphoma. The Drug Holds Promise for Addressing Resistance to First-Generation BTK Inhibitors.
APQ 531 is a reversible, second-generation oral BTK inhibitor.
Inclusion Criteria and Study DesignAn open-label, single-arm, dose-escalation Phase I clinical trial is ongoing.
APQ 531 demonstrates favorable profiles in terms of safety, pharmacokinetics, and antitumor activity.
AstraZeneca's PARP Inhibitor Olaparib
EU Approval for First-Line Treatment of BRCA-Mutated Ovarian Cancer
AstraZeneca Announces EU Approval of Lynparza (Olaparib), a PARP Inhibitor, for First-Line Treatment of Patients with BRCA-Mutated Advanced Ovarian Cancer.
Olaparib is a PARP inhibitor.
Inclusion Criteria and Study DesignThis approval is based on the randomized, double-blind, placebo-controlled, multicenter Phase 3 clinical trial SOLO-1.
At the 41-month follow-up, the median PFS had not been reached in the olaparib group, compared with 13.8 months in the placebo group. Meanwhile, 60% of patients in the olaparib group remained progression-free within 36 months of treatment, versus 27% in the placebo group.
CARsgen Therapeutics Announces ItsBCMA CAR-T Therapy IND Approved
CT053, a BCMA CAR-T therapy independently developed by CARsgen Therapeutics, has recently received IND approval from the FDA, becoming the first domestically originated CAR-T program to obtain independent IND clearance in the United States.
This therapy is an independently developed CAR-T therapy by Caris Biologics, utilizing a fully human antibody targeting BCMA.
Inclusion Criteria and Study DesignClinical trials have not yet been initiated.
Clinical trials have not yet been conducted.
AstraZeneca's Triple Therapy for COPDGlobalFirst Approved for Market Launch in Japan
AstraZeneca Announces Japanese Approval of Breztri Aerosphere, Its Triple Therapy for Chronic Obstructive Pulmonary Disease (COPD), Marking the First Global Approval for This Regimen
Breztri Aerosphere is a triple therapy consisting of three active ingredients: budesonide, glycopyrronium bromide, and formoterol fumarate.
Inclusion Criteria and Experimental DesignApproval based on the KRONOS randomized, double-blind Phase 3 clinical trial involving 1,900 patients with moderate-to-severe obstructive lung disease.
Trial data demonstrate that this triple therapy significantly improves patients' pulmonary function compared with the control group.
Melinda Submits sNDA for Broad-Spectrum Antibiotic Baxdela
Melinta Therapeutics Announces Submission of sNDA for Broad-Spectrum Antibiotic Baxdela (delafloxacin) to the FDA, Granted Priority Review; The sNDA Seeks to Expand Indications to Include Treatment of Community-Acquired Bacterial Pneumonia (CABP)
Baxdela is an innovative broad-spectrum antibiotic that is effective against both Gram-negative and Gram-positive bacteria and can treat methicillin-resistant Staphylococcus aureus (MRSA).
Inclusion Criteria and Study DesignThis application is based on the results of a randomized, double-blind, Phase 3 clinical trial.
The trial results demonstrated that Baxcela met the non-inferiority criteria compared with moxifloxacin in terms of efficacy.
Positive Results from New Anti-Aging Drug in Treating Osteoarthritis
UNITY Biotechnology’s investigational anti-apoptotic protein inhibitor UBX0101 achieved positive results in a Phase 1 trial for the treatment of moderate-to-severe knee osteoarthritis.
UNITY is an anti-apoptotic protein capable of selectively eliminating senescent cells.
Inclusion Criteria and Study DesignThe primary endpoint of the Phase I clinical trial is safety and tolerability.
The trial results indicate that changes in biomarkers are consistent with the elimination of senescent cells and potential improvement of the tissue microenvironment.
Novo Nordisk's Esperoct in the EU
Approved for the Treatment of Hemophilia A in Adolescents and Adults
Novo Nordisk’s long-acting coagulation factor VIII, Esperoct, has received marketing authorization in the European Union for the treatment of hemophilia A in adolescents and adults aged 12 years and older.
Esperoct is a recombinant form of coagulation factor FVIII concentrate.
Inclusion Criteria and Study DesignEsperoct conducted the largest pre-registration clinical trial in hemophilia A, enrolling 270 previously treated patients with severe hemophilia A.
Trial results demonstrated that Esperoct reduces the frequency of bleeding episodes, enables prophylaxis, and controls bleeding events.
Alnylam’s First Global RNAi Drug Approved for Launch in Japan
Alnylam Announces Approval of Onpattro, Its RNAi Therapeutic, in Japan for the Treatment of Hereditary Transthyretin (hATTR) Amyloidosis with Polyneuropathy. Onpattro Was Approved by the FDA in August 2018, Becoming the World’s First Approved RNAi Drug.
Onpattro is an RNAi therapeutic that inhibits the production of transthyretin.
Inclusion Criteria and Study DesignApproved based on the global Phase 3 clinical trial APOLLO, a randomized, double-blind, placebo-controlled study.
Trial results demonstrated that Onpattro improved patients’ neurological function, quality of life, activities of daily living, ambulatory ability, nutritional status, and autonomic symptoms, thereby meeting the primary endpoint and all secondary endpoints.
Figure: Structure of Onpattro
Source: Alnylam
Sumitomo Pharma Lonasen Tape
ChengThe World's First Approved Transdermal Patch for Antipsychotic Drugs
Sumitomo Pharma Announces Approval of Lonasen Tape (blonanserin) Transdermal Patch in Japan, Marking the World’s First Transdermal Patch Antipsychotic Drug
Lonasen tablets and powder were launched in Japan in 2008, and the patch technology for this launch is from Nippon Denko Co., Ltd.
Inclusion Criteria and Study DesignThe approval of this transdermal patch was based on a multinational, multicenter, randomized, placebo-controlled, double-blind Phase 3 study and a long-term, single-arm, open-label, continuous-treatment study.
Trial data demonstrate that Lonasen Tape significantly reduces the primary endpoint PANSS score, achieving therapeutic effects comparable to those of the tablet formulation.
❖At a recent investor conference, Merck & Co. stated that Keytruda is still in the early stages of development, with over 1,000 clinical trials currently underway. The next R&D objective is to utilize the drug as an adjuvant therapy for early-stage cancer.
❖Bluebird bio announced that the price of Zynteglo (LentiGlobin), its gene therapy for transfusion-dependent β-thalassemia recently approved in the European Union, is $1.77 million, making it the second most expensive drug globally, surpassed only by Novartis’ Zolgensma, a gene therapy for spinal muscular atrophy priced at $2.1 million. However, due to manufacturing issues, the market launch of the drug has been further delayed.
❖Gilead Sciences Announces Strategic Collaboration with Nurix Therapeutics to Develop Innovative Protein Degradation Drugs for Cancer and Other Challenging Diseases Using Nurix’s Proprietary Ubiquitin/E3 Ligase Platform
❖Pfizer recently announced the acquisition of Array BioPharma for $11.4 billion. Array BioPharma’s core platform focuses on kinase inhibitors, with its primary asset being the BRAF/MEK inhibitor combination Braftovi/Mektovi for the treatment of melanoma.
❖According to Reuters, GSK plans to sell some non-core products to cover the integration costs of its consumer health business with Pfizer. The products slated for sale include certain drug licenses in Latin America and Europe, as well as the Physiogel skincare brand.
❖Sanofi Announces 466 Job Cuts in France and Germany to Restructure R&D, Focusing on Oncology, Immunology, Rare Diseases, and Vaccines. The Company Also Halts New Research in Cardiology Indications and Narrows Diabetes Research to Treatments Addressing the Root Causes of the Disease.
❖Genzyme, a subsidiary of Sanofi, announced the termination of its collaboration with gene therapy company Voyager Therapeutics. The discontinued projects included VY-HTT01, a gene therapy for Huntington’s disease, and VY-FXN01, a gene therapy for Friedreich’s ataxia. In 2017, Sanofi had already abandoned its plan to collaborate with Voyager on VY-AADC, a gene therapy for Parkinson’s disease.
❖Beigene Announces Joint Venture with SpringWorks Therapeutics to Establish MapKure, Collaborating on the Development of Beigene’s Preclinical Candidate BGB-3245, an Oral, Highly Selective Small-Molecule Inhibitor Targeting Specific Monomeric and Dimeric B-RAF Activating Mutations with Potential for Treating Multiple Solid Tumors
❖SuoYuan Biopharma Announces Acquisition of Global Rights to Develop, Manufacture, and Commercialize Orion Corporation’s Novel Alzheimer’s Disease Drug ORM-12741. This innovative selective antagonist targeting the α-2C adrenergic receptor has undergone 11 clinical trials to date.
❖Hengrui Announces Exclusive License in China for Mycovia’s Patent-Lead Compound VT-1161, with a $7.5 Million Upfront Payment, $9 Million in R&D Milestone Payments, and Up to $92 Million in Sales Milestone PaymentsVT-1161 is a novel oral small-molecule selective fungal CYP51 inhibitor developed by Mycovia for the treatment of recurrent vulvovaginal candidiasis.
❖Akeso Biopharma Announces Joint Venture with Chia Tai Tianqing to Co-Develop Akeso’s Self-Developed PD-1 Antibody AK105. Chia Tai Tianqing will contribute RMB 345 million, while Akeso Biopharma will contribute its intellectual property and technical rights as intangible assets. Each party will hold a 50% equity stake, and Chia Tai Tianqing will obtain exclusive commercialization rights for AK105.
