Health & Beauty

China approves the listing of 3 new drugs

In July, my country approved a total of 3 new drugs, of which 2 new drugs were independently developed by Chinese pharmaceutical companies.

Carfilzomib is the third commercial product introduced in the strategic cooperation between BeiGene and Amgen. It is a second-generation proteasome inhibitor for the treatment of patients with relapsed/refractory multiple myeloma (MM) .

In a clinical phase III trial called ASPIRE, 792 patients with relapsed or refractory MM received the combination of carfilzomib + lenalidomide + dexamethasone (KRd) or lenalidomide + dexamethasone Methsone (Rd) regimen treatment. These patients have previously received 1 to 3 other therapies. The results of the test showed that the average overall survival (OS) of the KRd therapy group was 48.3 months, and the average OS of the Rd therapy group was 40.4 months. KRd therapy can prolong OS by 7.9 months. In the subgroup of patients who only received other therapies once, KRd therapy was more effective, and compared with Rd therapy, it could prolong the average OS by 11.4 months.

CMAB008 is a recombinant anti-TNF-α chimeric monoclonal antibody and a biological analogue of infliximab. Infliximab was first approved by the U.S. FDA for marketing in the United States in 1998, was approved for marketing in Europe the following year, and was approved for marketing in my country in 2006. The drug's global annual sales reached a maximum of 9.240 billion U.S. dollars. Despite the impact of biosimilar drugs, it still achieved 4.077 billion U.S. dollars in sales in 2020. At present, three other domestic companies have submitted applications for infliximab biosimilars, namely Hisun Pharmaceutical, Jiahe Biological and Celltrion.

Azivudine is the first HIV reverse transcriptase and accessory protein Vif dual-target inhibitor drug. The results of clinical studies have shown that the oral dose of Azivudine is extremely small. After 5 days of administration, the concentration of Azivudine is still higher than the concentration that inhibits half of the virus. It has the advantages of low-dose, multi-target, long-acting oral administration, and has the advantages of preventing HIV replication by 100% more than 4 days after administration, and is listed with conditions in advance with the results of phase II clinical trials.

The U.S. approves the listing of 4 new drugs

In July of this year, the United States approved four new drugs for marketing, all of which were approved through the accelerated approval channel. According to the Pharmadigger database, 3 of these products are the first batches in the world.

Finer enone is a third-generation, highly selective, non-steroidal corticosteroid receptor antagonist (MRA), which has higher mineralocorticoid receptor specificity than the first and second-generation MRAs Sex and affinity, can selectively bind to mineralocorticoid receptor. Its approval is based on a randomized, multi-center, double-blind study comparing the efficacy of finialidone tablets with placebo in 5674 patients with chronic kidney disease (CKD). Specifically, compared with the placebo group, the compound risk of kidney death in the Finerenone group was significantly reduced by 18%. In the pre-specified subgroups, the effects of Finerenone on the main outcome were broadly consistent, and the treatment effect was sustained throughout the study period.

Fexinidazole (fexinidazole) is the first oral drug for the treatment of sleeping sickness and is a DNA synthesis inhibitor. Current treatments for sleeping sickness include intramuscular injection of Pentamidine or intravenous infusion of Eflornithine. The convenience of oral therapy is very important for the treatment of sleeping sickness. Sanofi was awarded a U.S. FDA tropical disease priority review voucher.

Belumosudil is a new oral selective Rho-related coiled-coil protein kinase 2 (ROCK2) inhibitor, which can enhance regulatory T cells (Treg), rebalance immune response, and treat immune dysfunction. Belumosudil was submitted through the "Real-Time oncology Review (RTOR)" pilot project of the major innovative new oncology drug approval policy of the Oncology Center of Excellence (OCE) under the US FDA. Its approval is based on the results of a trial called ROCKStar. The trial included 66 patients with chronic graft-versus-host disease (cGVHD) who had previously received 2 to 5 systemic therapies. The optimal overall response rate (ORR) of Belumosudil 200 mg once daily and 200 mg twice daily were 74% and 77%, respectively. High response rates were observed in all subgroups. All affected organs showed a complete response. The median duration of response (DOR) was 54 weeks; 44% of subjects received treatment for more than 1 year.

Odevixibat is the first drug approved in the United States for the treatment of all subtypes of progressive familial intrahepatic cholestasis (PFIC) pruritus. It was also approved for marketing in the EU in July. PFIC is a rare and devastating disease that can affect children and cause progressive, life-threatening liver disease. The main problem of PFIC is itching or intense itching, which often leads to a serious decline in the quality of life of patients. Odevixibat is an effective, once-daily, non-systemic ileal bile acid transport inhibitor that acts locally in the small intestine. The medicine does not need to be refrigerated. It can be taken as a capsule for older children or sprinkled on food after opening.

The EU approves the listing of 5 new drugs

In July, the European Union approved the listing of 5 new drugs. Among them, Odevixibat and one-time gene therapy Elivaldogene autotemcel were approved for marketing for the first time in the world, and the rest were approved first in the United States.

Setmelanotide is an oligopeptide melanocortin 4 receptor (MC4R) agonist for the treatment of rare obesity genetic diseases. MC4R is a part of the key biological pathway that the body independently regulates energy expenditure and appetite. Setmelanotide has been approved by the US FDA in November 2020. The approval is based on two pre-opioid melanocyte corticosteroids (POMC), proprotein convertase subtilisin 1 (PCSK1) or leptin receptor (LEPR) Results of a 52-week phase III clinical trial in obese patients caused by genetic defects. The results of the test showed that 80% of obese patients with POMC or PCSK1 gene defects lost more than 10% of their weight after receiving Setmelanotide for one year, and 45.5% of obese patients with LEPR lost more than 10% of their weight.

Elivaldogene autotemcel is a one-time gene therapy drug for patients with cerebral adrenoleukodystrophy (CALD). CALD is an X-linked recessive genetic neurodegenerative disease. It is a more serious phenotype of adrenal leukodystrophy. It is caused by the pathogenic gene ABCD1 (ATP-binding Cassette, Sub-family D, Member I). Caused by the mutation. When the adrenal leukodystrophin (ALDP) encoding ABCD1 located on the peroxisome membrane is abnormal, this protein is responsible for transporting the fatty acid VLCFA (Very Long-chain Fatty Acid) to the peroxidase body for oxidation. The process is blocked, causing a large accumulation of white matter, adrenal cortex and other organs and tissues, and then causing central nervous system demyelination and adrenal atrophy. Elivaldogene autotemcel uses lentiviral vectors to introduce functional ABCD1 gene fragments into the patient's own hematopoietic stem cells, so that the patient's cells can produce functional ALDP protein, thereby removing the accumulated VLCFA.

This approval is based on the results of the pivotal Phase II/III Starbeam study (ALD-02). The main efficacy endpoint of the trial is the survival without major dysfunction (MFD). 90% of patients reached the MFD-free survival endpoint at the 24th month, and the neurological function of most patients was maintained.