9 Rare Disease Drugs Poised for Accelerated Approval in China in 2024

▎WuXi AppTec Content Team Report

Today (February 29) is International Rare Disease Day. In the past year, China has seen many significant advancements in the field of rare diseases, includingThe Highly Anticipated List of the "Second Batch of Rare Disease Catalog"Out of the Oven, as well as the approval and market launch of multiple rare disease therapies in China. In the past two months of 2024 alone, at least five new rare disease drugs have been approved in China, including trientine hydrochloride tablets (a copper chelating agent), crovalimab injection (a C5 inhibitor), zinc acetate tablets (a copper absorption inhibitor), teduglutide (a GLP-2 analog), and recombinant porcine factor VIII (rpFVIII) susoctocog alfa for injection, providing...Hepatolenticular Degeneration (Wilson's Disease), Paroxysmal Nocturnal Hemoglobinuria, Short Bowel Syndrome, Acquired Hemophilia A...and other diseases have brought new treatment options.

Looking Forward to 2024, What ElseAre New Rare Disease Drugs Expected to Be Approved for Marketing in China and Benefit Patients?Combined with the priority review and approval information disclosed on the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA),Share9Payment*New rare disease drugs expected to be approved in China this year are for readers' reference only.*Note: This article only shares some of the new drugs (tentatively) included in the priority review by the CDE, which is not an exhaustive list, and is sorted by the publication date of the CDE's priority review.

Huadong Medicine: Rilonacept for Injection (Tentative)

Mechanism of Action: IL-1 Inhibitor

Indications: CAPS,RP

Rilonacept for Injection isAIL-1 Inhibitor, by Huadong Medicine's wholly-owned subsidiary, Sinopharm HuadongIn collaboration with Kiniksa Pharmaceuticals' wholly-owned subsidiary, Huadong Medicine Co., Ltd.PossessThe ProductExclusive license in 24 Asia-Pacific countries and regions including China (excluding Japan), encompassing development, registration, and commercialization rights.In January and December 2023, the product was successively included in the priority review by the CDE, respectively targetingAdults and adolescents aged 12 years and aboveCryopyrin-Associated Periodic Syndromes (CAPS), adults and adolescents aged 12 years and above with recurrent pericarditis (RP).

Takeda（Takeda）: Vonicog alfa for injection

Mechanism of Action: Recombinant Von Willebrand Factor

Indications: Von Willebrand Disease

Vonicog alfa for injection is a product developed by Takeda.Recombinant Von Willebrand FactorIn January 2023, the product's marketing application was included in the priority review by the CDE for the indication ofAdult Patients with Von Willebrand Disease (VWD), including on-demand treatment and control of bleeding events, as well as perioperative bleeding management.

Von Willebrand disease is one of the common hereditary bleeding disorders, primarily due toVon Willebrand Factor (VWF) Gene MutationReduced quantity or abnormal quality of von Willebrand factor in plasma. When von Willebrand factor is dysfunctional or deficient, blood cannot clot effectively, leading to varying degrees of bleeding manifestations, and severe cases may result in visceral bleeding.Vonicog alfa for injection contains complete VWF multimers, including ultra-large multimers, with a long half-life. It can effectively achieve replacement therapy for von Willebrand disease and provide patients with personalized bleeding control methods.. The product has beenCountries such as the United States, Canada, and the United KingdomApproved for the treatment of vascular hemophilia.

Novartis: Eptinezumab Capsules

Mechanism of Action: Inhibitor of Complement Pathway Factor B

Indications: Adult Paroxysmal Nocturnal Hemoglobinuria

Iptacopan is developed by Novartis.An Oral Inhibitor Targeting the Complement Alternative Pathway B FactorIn June 2023, the marketing application for Ipecac Hydrochloride Capsules was included in the priority review by the CDE, intended for the treatment ofAdult Paroxysmal Nocturnal Hemoglobinuria (PNH)Patient.

PNH isA Rare Blood Disease Mediated by Complement, the patient's hematopoietic stem cellsPIG-AGene mutations lead to the production of red blood cells that are prone to premature destruction by the complement system, causing both intravascular and extravascular hemolysis. Current C5 inhibitor treatments are administered through infusion and may not adequately control PNH symptoms; a significant proportion of patients still experience residual anemia and remain transfusion-dependent even after receiving anti-C5 therapy.

Iptacopan is a B factor inhibitor，Factor B Drives Complement-Mediated in PNHHemolysis. The drug works throughActs on the proximal pathway of the complement alternative pathway in the immune system, providing comprehensive control over intravascular and extravascular red blood cell destruction (intravascular and extravascular hemolysis).。The drug was approved by the U.S. FDA in December 2023 as an oral monotherapy for adult PNH.

Yuanyi Biotechnology: Ganaxolone Oral Suspension

Mechanism of Action: GABAA Receptor-Targeting Positive Allosteric Modulator

Indications: CDKL5 Deficiency Disorder

GanaxoloneOral Suspension(Ganaxolone) is a product developed by Marinus.Positive allosteric modulators targeting GABAA receptors,Yuanyi BiotechnologyThrough a collaboration exceeding $260 million, it has obtained exclusive rights for development and commercialization in Greater China.In September 2023, the new drug application of this product was included in the priority review by the CDE.ProposedFor the treatment of seizures in patients aged 2 years and above with cyclin-dependent kinase 5 (CDKL5) deficiency. CDKL5 deficiency has been included in China's "Second Batch of Rare Disease Catalog."

Epileptic seizures associated with CDKL5 deficiency disorder are a rare form of genetic epilepsy. CDKL5 deficiency disorder is caused by mutations located on the X chromosome.CDKL5Caused by genetic mutations, the disease is characterized by intractable epileptic seizures and severe neurodevelopmental disorders.GanaxoloneActs on neuronal synaptic and extrasynaptic GABAA receptors, thereby achieving antiepileptic and anxiolytic activity.。Ganaxolone Oral Suspension Previously Received FDA Approval for Marketing, Used to Treat Seizures in Patients Over Two Years Old Associated with CDKL5 Deficiency Disorder.

Novo Nordisk: Recombinant Factor VIII (Pegylated) for Injection

Mechanism of Action: Long-acting Recombinant Factor VIII

Indications: Hemophilia A in adults and children

Turoctocog Alfa Pegol for Injection is a product developed by Novo Nordisk.Long-acting Recombinant Factor VIII (FVIII)In September 2023, the CDE included the product's marketing application in the priority review, intended for use in adult and pediatric patients with Hemophilia A (congenital Factor VIII deficiency).

Hemophilia A is a rare hereditary hemorrhagic disease caused by the deficiency of coagulation factor VIII, with repeated bleeding and its related complications as the main clinical manifestations. If repeated bleeding is not treated in time, it can lead to joint deformities or pseudotumor formation, and severe cases can be life-threatening. Currently, the main treatment for hemophilia A is regular infusion of coagulation factor VIII, but frequent infusions bring great inconvenience to patients' lives.The half-life of PEGylated perturocoagulase α for injection is significantly prolonged.Compared with non-modified FVIII products, the half-life of this product is extended by 1.6 times in adults/adolescents and 1.9 times in children.. The product has previously been approved by the FDA.For prophylactic and acute treatment in adult and pediatric patients with hemophilia A.

Ruikangdi Pharmaceuticals: Osimertinib Phosphate Film-Coated Tablets

Mechanism of Action: Cortisol Synthesis Inhibitor

Indications: Cushing's Syndrome

Oxistat Phosphate Film-Coated Tablets are aNovel Oral Cortisol Synthesis InhibitorIn October 2023, the film-coated tablets of osilodrostat phosphate submitted by Recordati Group's wholly-owned Chinese subsidiary, RuiKangDi Pharmaceuticals, were included in the priority review by the CDE.Intended for the treatment of adult endogenous Cushing's syndrome (also known as endogenous hypercortisolism)。

Cushing's syndrome is a group of symptoms caused by excessive cortisol secretion from the adrenal cortex due to various etiologies over a long period.Cushing's SyndromeMore common in adults aged 40-45, with more females than males. The most important and common complications of this disease include hypertension, diabetes, osteoporosis, and metabolic syndrome. Therefore, most patients die from cardiovascular or cerebrovascular diseases or severe infections.Oxistat Phosphate Film-Coated TabletsBy blocking adrenal cortisol synthesis, it inhibits the excessive production of cortisol, thereby controlling or normalizing cortisol levels in adult patients.. The product has been approved in the European Union, the United States, and other regions for the treatment of adult Cushing's disease.。

Ipsen: Odevixibat Capsules

Mechanism of Action: IBAT Inhibitor

Indications: Progressive Familial Intrahepatic Cholestasis (PFIC)

Odevixibat is aStrongEfficacy, Non-Systemic Circulating Ileal Bile Acid Transporter (IBAT) InhibitorIpsen announced the completion of its acquisition of Albireo Pharma in March 2023, thereby gaining access to the latter's product. In November 2023,Odevixibat capsules have been included in the priority review by the CDE for the proposed use ofTreatment of Progressive Familial Intrahepatic Cholestasis (PFIC) in Patients for 6 Months or Longer。

PFIC is a rare genetic disorder that can lead to progressive liver disease and has been included in the "First List of Rare Diseases" in China.。PFIC patients have a reduced ability to secrete bile in the liver, and the accumulation of bile within the liver can lead to liver disease, with severe cases resulting in liver failure.The signs and symptoms of this disease usually begin in infancy, with patients experiencing severe itching, jaundice, slow growth or failure to thrive, and gradual loss of liver function.Odevixibat CapsulesCan block intestinal bile acids from re-entering the liver through the enterohepatic circulation, thereby reducing the concentration of bile acids within the liver and in circulation.The ProductAlready approved in the U.S. for treatment 3 months agoAgePruritus in PFIC patients and above.

Shugfang Pharmaceuticals: Vamorolone Oral Suspension

Mechanism of Action:Steroid drugs

Indications: Duchenne Muscular Dystrophy (DMD)

Vamorolone Oral Suspension is a rare disease new drug that Sperogenix Therapeutics introduced from Santhera Pharmaceuticals for $124 million. It was proposed by the CDE to be included in the priority review in February 2024 and is intended for the treatment of...DMD patients aged 4 years and above。DMD is a fatal rare X-linked degenerative neuromuscular disease and also one of the most common lethal genetic disorders. Shortly after birth, patients exhibit inflammatory responses, leading to muscle fibrosis as well as muscle atrophy and degeneration. Due to respiratory or cardiac failure, the life expectancy of patients typically does not exceed 40 years.Corticosteroids are the standard treatment for DMD patients.These hormones, while able to delay disease progression, have some side effects.。

Vamorolone is an original new drug. Its mechanism of action is the same as the receptor bound by glucocorticoids but alters its downstream activity. It is not a substrate for 11-β-hydroxysteroid dehydrogenase, thereforeWill not cause local tissue expansion and corticosteroid-related toxicity in local tissues. This mechanism showsVamorolone has the potential to "separate" efficacy from hormonal safety concerns.`, is expected to bring a safer treatment option for children and adolescents with DMD. The product`Previously approved for the treatment of DMD in the United States and the European Union.

MSD: Belzutifan Tablets

Mechanism of Action: HIF-2α Inhibitor

Indications: VHL-associated renal cell carcinoma, etc.

Belzutifan is aSelective Novel Oral HIF-2α Inhibitor. In February 2024, the product was proposed by the CDE for priority review, targeting indications such as von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET).

VHL is a rare genetic disease that can abnormally activate hypoxia-inducible factor (HIF-2α) in cancer patients, leading to the accumulation of HIF-2α in the body and causing the formation of benign and malignant tumors. Research related to the HIF-2α pathway won the Nobel Prize in Physiology or Medicine in 2019. Belzutifan has previously been approved by the FDA for the treatment of VHL-related cancers.

In addition to the aforementioned products, some rare drugs are also expected to be approved for marketing in China in 2024. Due to space limitations, this article will not introduce them one by one.We hope that these innovative therapies will be approved in China as soon as possible, bringing new treatment options to patients!