Inventory of new drugs approved for listing in China, the United States and Europe in March

In March, China, the United States and Europe approved a total of 11 new drugs for the market
.
Among them, China approved 7 models, the United States approved 3 models, and the EU approved 1 model
.

 

China approves 7 new drugs for the market

 

Among the 7 new drugs approved for marketing, slulimumab is a new drug independently developed by Chinese pharmaceutical company Fuhong Henlius, and it is also the 13th PD-1/PD-L1 antibody drug marketed in China
.

 

Slulimumab is approved for patients with unresectable or metastatic high-grade microsatellite instability (MSI-H) solid tumors who have failed standard
therapy .
In the classification of MSI, two or more site changes are called MSI-H, which are commonly seen in endometrial cancer, colorectal cancer, gastric cancer, etc.
, and related patients usually respond to PD-1/PD-L1 antibody drugs have a higher response rate
.
At present, the indications of slulimumab for non-small cell lung cancer and small cell lung cancer have also submitted marketing applications in China
.

 

　　Ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist, which can specifically bind to VEGFR2 and block the binding of this receptor to VEGF-A, C, and D.
Inhibit tumor tissue angiogenesis to achieve anti-tumor effect
.
In April 2014, the drug was approved by the U.
S.
Food and Drug Administration (FDA) as a second-line treatment for advanced gastric cancer, and it is also the world's first targeted drug approved for second-line treatment of advanced gastric cancer
.
On January 12, 2021, Eli Lilly announced the latest update on ramucirumab, with or without paclitaxel, for the treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma that is resistant or progressive after first-line platinum and fluorouracil therapy.
The Asian Phase III study RAINBOW-Asia met the prespecified study endpoint
.
The results of the study showed that the progression-free survival of patients in the ramucirumab combined with paclitaxel group was significantly longer than that in the placebo group
.

 

　　Brigatinib is a new generation of potent and selective tyrosine kinase inhibitor (TKI) targeting fusion mutations in anaplastic lymphoma kinase (ALK), and its unique dimethyl phosphine oxide (DMPO) structure strengthens the interaction with ALK protein The binding force of ALK enhances the activity of the drug, and also creates favorable conditions for the drug to pass through the blood-brain barrier and maintain the blood concentration in the brain.
At the same time, it can widely inhibit a variety of ALK fusion types and drug resistance mutations
.
Brigatinib was approved for marketing in the United States as early as April 2017 for patients with advanced ALK-positive non-small cell lung cancer whose disease has progressed after crizotinib treatment or who are intolerant to crizotinib
.
In May 2020, its indication was further expanded: the US FDA approved its first-line treatment of adult patients with ALK-positive metastatic NSCLC
.

 

　　Neuromyelitis optica spectrum disorder (NMOSD) is a rare, severe, relapsing neuroinflammatory autoimmune disorder characterized by inflammatory lesions of the optic nerve and spinal cord
.
In May 2018, the disease was included in the first batch of rare diseases in China
.
Inelizumab is a humanized monoclonal antibody with high affinity for CD19 developed by Viel a Bio.
By binding to the CD19 antigen, it can rapidly remove these cells from the blood circulation, thereby reducing the production of autoantibodies , in order to achieve the purpose of improving the symptoms of NMOSD patients
.
In May 2019, Hansoh Pharma obtained the rights to develop and commercialize the drug in China from Viel a Bio
.
At present, no other CD19 mAb has been approved for marketing in China
.

 

　　Epravacizumab is a fully humanized monoclonal antibody targeting interferon gamma (IFN-γ) developed by Swedish Orphan Biovitrum (Sobi) and Light Chain.
IFN-γ binds and neutralizes its biological activity
.
In patients with hemophagocytic lymphoproliferative syndrome (HLH), the release of cytotoxic granules is blocked, which impairs cytotoxic function and leads to impaired antigen clearance, while T cells bind to target cells and can continuously produce cytokines, such as IFN-γ, IL-12, IL-18, TNF-α, etc.
, eventually lead to organ failure
.
Among them, IFN-γ is the key and upstream mediator of HLH, so reducing the level of IFN-γ is particularly important for the treatment of HLH
.
Ipravalumab was first launched in the United States in November 2018 and is the only drug approved globally for the treatment of primary HLH and the first drug specifically targeting IFN-γ
.

 

　　Duvelise is a dual inhibitor of PI3K-delta and PI3K-gamma developed by Verast em
.
PI3K signaling may lead to the proliferation of malignant B cells and play an important role in the formation and maintenance of the tumor microenvironment.
Targeting two protein kinases, PI3K-δ and PI3K-γ, has been clinically proven to effectively inhibit malignant B cells and Inhibition of PI3K-δ leads to apoptosis of malignant tumor cells, while inhibition of PI3K-γ reduces Sertoli cell differentiation and metastasis in the tumor microenvironment
.
In September 2018, CSPC signed an agreement with Verastem to obtain the latter's exclusive license to develop and commercialize Doveliser in Greater China
.

 

　　Pratinib is a highly selective oral inhibitor targeting oncogenic transfection rearrangement (RET) variants, RET-activating fusions and mutations that are key disease drivers in many cancer types
.
About 1% to 2% of non-small cell lung cancer patients and about 10% to 20% of papillary thyroid cancer patients carry RET fusions, and about 90% of advanced medullary thyroid cancer (MTC) patients carry RET mutations
.
Pratinib was first approved by the U.
S.
FDA in September 2020, and is currently approved for the treatment of adult patients with metastatic RET fusion-positive NSCLC, adults with advanced or metastatic RET-mutant medullary thyroid cancer requiring systemic therapy, and Pediatric patients 12 years of age and older , as well as adults and children 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer requiring systemic therapy and refractory to radioactive iodine (if applicable)
.
In June 2018, CStone acquired the exclusive development and commercialization rights of Pratinib in Greater China through a partnership with Blueprint Medicines
.

 

3 new drugs 　　approved in the U.
S.

 

　　According to the Pharmadigger database, the three new drugs approved for marketing in the United States in March were the first in the world
.

 

　　Ganaxolone (brand name Ztalmy) is the first FDA-approved therapy to treat seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency (CDD) in patients older than two years of age
.
The disorder is a rare inherited form of epilepsy characterized by uncontrollable seizures and severe neurodevelopmental impairment for which no prior therapies have been approved
.

 

　　Ganaxolone is a neuroactive steroid that acts as a GABAA receptor-positive allosteric modulator
.
GABA is one of the inhibitory neurotransmitters in the central nervous system, which is related to emotional changes such as anxiety, tension and depression.
Therefore, acting on this receptor can achieve anti-epileptic and anti-anxiety activities
.
Ganaxolone was granted orphan drug designation and rare pediatric disease (RPD) designation for the treatment of CDKL5 deficiency diseases in June 2017 and July 2020, respectively; in September 2021, its new drug application was granted priority review by the US FDA
.
This time it is listed as an oral suspension, which is more convenient for children to take
.

 

　　The lymphocyte activation gene 3 (LAG-3) antibody drug Relatlimab in the fixed-dose antibody combination therapy of Relatlimab and Nivolumab (trade name Opdualag) is the first LAG-3 antibody approved by the US FDA, and its approval is based on a II/ Efficacy and safety results of phase III clinical trials
.
In 2021, data published by the American Society of Clinical Oncology (ASCO) showed that the combination therapy of Relatlimab and Nivolumab resulted in a statistically and clinically significant benefit in progression-free survival (PFS) in patients with melanoma compared to Nivolumab monotherapy
.

 

　　LAG-3 is a cell surface molecule expressed on effector T cells and regulatory T cells (Tregs) and functions to control T cell response, activation and growth
.
Early research suggests that inhibition of LAG-3 restores T-cell effector function and may promote anti-tumor responses
.
LAG-3 can be used in combination with other potentially complementary immune checkpoints, such as co-expression with PD-1 on tumor-infiltrating lymphocytes, so combination therapy targeting these two targets is an effective strategy to enhance anti-tumor immune activity one
.

 

　　Lutetium Lu 177 vipivotide tetraxetan (trade name Pluvicto) is the first targeted radioligand-targeted therapy approved by the US FDA for the treatment of patients with PSMA-positive mCRPC
.
The drug consists of a targeting compound (ligand) combined with a therapeutic radionuclide that binds to PSMA-expressing prostate cancer cells and causes DNA damage to kill tumor cells through beta rays emitted when the radionuclide 177Lu decays
.
PSMA is highly expressed in more than 80% of prostate cancer patients and thus has a high selective tumor-killing effect
.

 

　　EU approves 1 new drug

 

　　The new drug approved by the European Union in March is a combination product of Tixagevimab and Cilgavimab (trade name Evusheld)
.
The product is administered by intramuscular injection at different sites, and is suitable for people who are not currently infected or exposed to the new coronavirus and have difficulty developing sufficient antibody protection against the new coronavirus vaccine, including those who are not recommended to be vaccinated
.

 

　　The two antibodies, first discovered by Vanderbilt University Medical Center, are derived from B cells of recovered patients and can bind to different sites on the SARS-CoV-2 spike protein
.
AstraZeneca optimized both antibodies to increase half-life and reduce Fc receptor and complement C1q binding
.
The prolonged half-life results in increased persistence of action compared to conventional antibodies
.

　　In March, China, the United States and Europe approved a total of 11 new drugs for the market
.
Among them, China approved 7 models, the United States approved 3 models, and the EU approved 1 model
.

 

　　China approves 7 new drugs for the market

 

　　Among the 7 new drugs approved for marketing, slulimumab is a new drug independently developed by Chinese pharmaceutical company Fuhong Henlius, and it is also the 13th PD-1/PD-L1 antibody drug marketed in China
.

 

　　Slulimumab is approved for patients with unresectable or metastatic high-grade microsatellite instability (MSI-H) solid tumors who have failed standard
therapy .
In the classification of MSI, two or more site changes are called MSI-H, which are commonly seen in endometrial cancer, colorectal cancer, gastric cancer, etc.
, and related patients usually respond to PD-1/PD-L1 antibody drugs have a higher response rate
.
At present, the indications of slulimumab for non-small cell lung cancer and small cell lung cancer have also submitted marketing applications in China
.

 

　　Ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist, which can specifically bind to VEGFR2 and block the binding of this receptor to VEGF-A, C, and D.
Inhibit tumor tissue angiogenesis to achieve anti-tumor effect
.
In April 2014, the drug was approved by the U.
S.
Food and Drug Administration (FDA) as a second-line treatment for advanced gastric cancer, and it is also the world's first targeted drug approved for second-line treatment of advanced gastric cancer
.
On January 12, 2021, Eli Lilly announced the latest update on ramucirumab, with or without paclitaxel, for the treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma that is resistant or progressive after first-line platinum and fluorouracil therapy.
The Asian Phase III study RAINBOW-Asia met the prespecified study endpoint
.
The results of the study showed that the progression-free survival of patients in the ramucirumab combined with paclitaxel group was significantly longer than that in the placebo group
.

 

　　Brigatinib is a new generation of potent and selective tyrosine kinase inhibitor (TKI) targeting fusion mutations in anaplastic lymphoma kinase (ALK), and its unique dimethyl phosphine oxide (DMPO) structure strengthens the interaction with ALK protein The binding force of ALK enhances the activity of the drug, and also creates favorable conditions for the drug to pass through the blood-brain barrier and maintain the blood concentration in the brain.
At the same time, it can widely inhibit a variety of ALK fusion types and drug resistance mutations
.
Brigatinib was approved for marketing in the United States as early as April 2017 for patients with advanced ALK-positive non-small cell lung cancer whose disease has progressed after crizotinib treatment or who are intolerant to crizotinib
.
In May 2020, its indication was further expanded: the US FDA approved its first-line treatment of adult patients with ALK-positive metastatic NSCLC
.

 

　　Neuromyelitis optica spectrum disorder (NMOSD) is a rare, severe, relapsing neuroinflammatory autoimmune disorder characterized by inflammatory lesions of the optic nerve and spinal cord
.
In May 2018, the disease was included in the first batch of rare diseases in China
.
Inelizumab is a humanized monoclonal antibody with high affinity for CD19 developed by Viel a Bio.
By binding to the CD19 antigen, it can rapidly remove these cells from the blood circulation, thereby reducing the production of autoantibodies , in order to achieve the purpose of improving the symptoms of NMOSD patients
.
In May 2019, Hansoh Pharma obtained the rights to develop and commercialize the drug in China from Viel a Bio
.
At present, no other CD19 mAb has been approved for marketing in China
.

 

　　Epravacizumab is a fully humanized monoclonal antibody targeting interferon gamma (IFN-γ) developed by Swedish Orphan Biovitrum (Sobi) and Light Chain.
IFN-γ binds and neutralizes its biological activity
.
In patients with hemophagocytic lymphoproliferative syndrome (HLH), the release of cytotoxic granules is blocked, which impairs cytotoxic function and leads to impaired antigen clearance, while T cells bind to target cells and can continuously produce cytokines, such as IFN-γ, IL-12, IL-18, TNF-α, etc.
, eventually lead to organ failure
.
Among them, IFN-γ is the key and upstream mediator of HLH, so reducing the level of IFN-γ is particularly important for the treatment of HLH
.
Ipravalumab was first launched in the United States in November 2018 and is the only drug approved globally for the treatment of primary HLH and the first drug specifically targeting IFN-γ
.

 

　　Duvelise is a dual inhibitor of PI3K-delta and PI3K-gamma developed by Verast em
.
PI3K signaling may lead to the proliferation of malignant B cells and play an important role in the formation and maintenance of the tumor microenvironment.
Targeting two protein kinases, PI3K-δ and PI3K-γ, has been clinically proven to effectively inhibit malignant B cells and Inhibition of PI3K-δ leads to apoptosis of malignant tumor cells, while inhibition of PI3K-γ reduces Sertoli cell differentiation and metastasis in the tumor microenvironment
.
In September 2018, CSPC signed an agreement with Verastem to obtain the latter's exclusive license to develop and commercialize Doveliser in Greater China
.

 

　　Pratinib is a highly selective oral inhibitor targeting oncogenic transfection rearrangement (RET) variants, RET-activating fusions and mutations that are key disease drivers in many cancer types
.
About 1% to 2% of non-small cell lung cancer patients and about 10% to 20% of papillary thyroid cancer patients carry RET fusions, and about 90% of advanced medullary thyroid cancer (MTC) patients carry RET mutations
.
Pratinib was first approved by the U.
S.
FDA in September 2020, and is currently approved for the treatment of adult patients with metastatic RET fusion-positive NSCLC, adults with advanced or metastatic RET-mutant medullary thyroid cancer requiring systemic therapy, and Pediatric patients 12 years of age and older , as well as adults and children 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer requiring systemic therapy and refractory to radioactive iodine (if applicable)
.
In June 2018, CStone acquired the exclusive development and commercialization rights of Pratinib in Greater China through a partnership with Blueprint Medicines
.

 

3 new drugs 　　approved in the U.
S.

 

　　According to the Pharmadigger database, the three new drugs approved for marketing in the United States in March were the first in the world
.

 

　　Ganaxolone (brand name Ztalmy) is the first FDA-approved therapy to treat seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency (CDD) in patients older than two years of age
.
The disorder is a rare inherited form of epilepsy characterized by uncontrollable seizures and severe neurodevelopmental impairment for which no prior therapies have been approved
.

 

　　Ganaxolone is a neuroactive steroid that acts as a GABAA receptor-positive allosteric modulator
.
GABA is one of the inhibitory neurotransmitters in the central nervous system, which is related to emotional changes such as anxiety, tension and depression.
Therefore, acting on this receptor can achieve anti-epileptic and anti-anxiety activities
.
Ganaxolone was granted orphan drug designation and rare pediatric disease (RPD) designation for the treatment of CDKL5 deficiency diseases in June 2017 and July 2020, respectively; in September 2021, its new drug application was granted priority review by the US FDA
.
This time it is listed as an oral suspension, which is more convenient for children to take
.

 

　　The lymphocyte activation gene 3 (LAG-3) antibody drug Relatlimab in the fixed-dose antibody combination therapy of Relatlimab and Nivolumab (trade name Opdualag) is the first LAG-3 antibody approved by the US FDA, and its approval is based on a II/ Efficacy and safety results of phase III clinical trials
.
In 2021, data published by the American Society of Clinical Oncology (ASCO) showed that the combination therapy of Relatlimab and Nivolumab resulted in a statistically and clinically significant benefit in progression-free survival (PFS) in patients with melanoma compared to Nivolumab monotherapy
.

 

　　LAG-3 is a cell surface molecule expressed on effector T cells and regulatory T cells (Tregs) and functions to control T cell response, activation and growth
.
Early research suggests that inhibition of LAG-3 restores T-cell effector function and may promote anti-tumor responses
.
LAG-3 can be used in combination with other potentially complementary immune checkpoints, such as co-expression with PD-1 on tumor-infiltrating lymphocytes, so combination therapy targeting these two targets is an effective strategy to enhance anti-tumor immune activity one
.

 

　　Lutetium Lu 177 vipivotide tetraxetan (trade name Pluvicto) is the first targeted radioligand-targeted therapy approved by the US FDA for the treatment of patients with PSMA-positive mCRPC
.
The drug consists of a targeting compound (ligand) combined with a therapeutic radionuclide that binds to PSMA-expressing prostate cancer cells and causes DNA damage to kill tumor cells through beta rays emitted when the radionuclide 177Lu decays
.
PSMA is highly expressed in more than 80% of prostate cancer patients and thus has a high selective tumor-killing effect
.

 

　　EU approves 1 new drug

 

　　The new drug approved by the European Union in March is a combination product of Tixagevimab and Cilgavimab (trade name Evusheld)
.
The product is administered by intramuscular injection at different sites, and is suitable for people who are not currently infected or exposed to the new coronavirus and have difficulty developing sufficient antibody protection against the new coronavirus vaccine, including those who are not recommended to be vaccinated
.

 

　　The two antibodies, first discovered by Vanderbilt University Medical Center, are derived from B cells of recovered patients and can bind to different sites on the SARS-CoV-2 spike protein
.
AstraZeneca optimized both antibodies to increase half-life and reduce Fc receptor and complement C1q binding
.
The prolonged half-life results in increased persistence of action compared to conventional antibodies
.