Novo Nordisk’s recombinant coagulation factor Ⅷ (turoctocog alfa, trade name: Novoeight) has recently been applied for marketing in China for the treatment of hemophilia A. Chiatai Tianqing previously completed the relevant Phase III clinical trial ahead of Novo Nordisk, however, Novo Nordisk filed the marketing application to the NMPA ahead of Chiatai Tianqing.
As a B-domain truncated recombinant human coagulation factor Ⅷ, turoctocog alfa is used to prevent and treat bleeding in patients with hemophilia A; it is the third-generation recombinant coagulation factor Ⅷ product of Novo Nordisk and uses the latest gene recombination and protein purification techniques; it received FDA’s approval in Oct. 2013.
Turoctocog alfa was evaluated in the Guardian Phase III trials which have been so far the largest clinical pre-registered trial project conducted in hemophilia A patients, involving more than 200 hemophilia A patients. Those Phase III clinical trials conducted by Novo Nordisk included previously treated severe hemophilia A adult and child patients, of which the results proved the prevention and therapeutic effects of turoctocog alpha against bleeding, without inhibitor occurring inside patients.
Global annual sales of Novo Nordisk’s Novoeight and Novoseven are around USD2 billion at present.
Related news: Market shares of overseas pharma enterprises approach 70% in China’s coagulation factor Ⅷ market
Long-acting recombinant coagulation factors become the future R&D trend
Hemophilia is a group of hemorrhagic diseases with inherited coagulation disorder and belongs to a rare disease, with the common characteristics of active thromboplastin generation disorder, prolonged coagulation time, lifelong slight post-trauma bleeding tendency, and severe patients possibly having "spontaneous" bleeding even without obvious trauma. Hemophilia is generally divided into type A, type B, and type C according to the factor deficiencies, wherein, hemophilia A patients as a result of the deficiency of coagulation factor Ⅷ account for 80%-85% of the total hemophilia patients.
Type | Factor deficient | Patient proportion | Disease characteristic |
Hemophilia A | Coagulation factor Ⅷ |
>80%
| It is an X-linked recessive disorder, therefore, the proportion of male patients is far higher than that of female patients: the prevalence in baby boys is around one per five thousand to ten thousand |
Hemophilia B | Coagulation factor Ⅸ | <20% | The proportion of female patients is higher than that of male patients; the prevalence in babies is around one per twenty thousand to thirty-four thousand |
Hemophilia C | Coagulation factor Ⅺ | Very small | Autosomal recessive inherited disorder |
(Source: CNKI)
The inheritance mode of hemophilia is X-linked recessive inheritance and the gene is carried throughout patients’ lives, which still cannot be cured at present. The current therapeutic methods are all replacement therapy, with coagulation factors being the main drugs for hemophilia, wherein, coagulation factor Ⅷ is a kind of glycoprotein with molecular weight reaching over one million and it is dissociated to subunits with molecular weight of about 200,000 under high salt concentration to serve as the cofactor of coagulation factor IXa in the coagulation process and participate in the activation of the coagulation factor X; it is mainly used to treat hemophilia A.
Hemophilia replacement therapies have so far undergone three generations, and the long-acting coagulation factors will be the future R&D trend.
Time | Classification | Representative product | Advantages | Disadvantages |
1969 | First-generation product: plasma-derived coagulation factors | Plasma-derived FⅧ, plasma-derived FIX | Plasma extract, the upstream plasma collected amount deciding the ceiling of the drug production | Raw materials not easy to obtain; humanized product possibility causing blood-borne infections |
1992 | Second-generation product: recombinant coagulation factors | Recombinant FⅧ, recombinant FIX | Replacing albumin with inorganic sucrose, etc. to avoid the possibility of human-derived infection; the developed recombination technology allowing coagulation factors to get rid of dependence on plasma | The frequent injections every week bringing much pain to patients and possibly causing phlebitis |
2014 | Third-generation product: long-acting recombinant coagulation factors | Produced obtained based on the second generation through methods of PEG modification, B-domain glycosylation, Fc fusion protein, albumin fusion protein, and bispecific antibody, etc. | Prolonging the product half-life for more than one time; replacing intravenous injection with subcutaneous injection | Not able to cure the disease compared to gene therapy |
(Sorted out according to public data)
Novo Nordisk has applied for the marketing of its product ahead of Chiatai Tianqing, however, Chiatai Tianqing’s product is a long-acting variety
Chinese and overseas pharmaceutical enterprises and medical product suppliers are actively laying out recombinant coagulation factor Ⅷ in China. The following pharmaceutical enterprises are now conducting Phase III clinical trials of their products. Novo Nordisk has applied for the marketing of its product ahead Chiatai Tianqing.
It's worth mentioning that products of Furen Medicines and Chiatai Tianqing are both the third-generation long-acting recombinant human coagulation factor Ⅷ-Fc fusion protein, which have significant advantages over the second-generation product of Novo Nordisk.
Registration No. | Trial status | Applicant’s name | Drug name | Indication | Trial purpose |
CTR20160811 | Applied for marketing | Novo Nordisk China | Recombinant Human Coagulation Factor Ⅷ for Injection | Hemophilia A | To assess the clinical effectiveness of turoctocog alfa in treating bleeding in severe hemophilia A patients in China (coagulation factor Ⅷ <1%) |
CTR20160253 | Completed | Chiatai Tianqing | Recombinant Human Coagulation Factor皿 for Injection | Hemophilia A | To evaluate the effectiveness and safety of the recombinant human coagulation factor 皿 in treating and preventing the bleeding of hemophilia A patients |
-- | Clinical approval received | Furen Medicines | Recombinant Human Coagulation Factor Ⅷ- Fc Fusion Protection for Injection | Hemophilia | -- |
CTR20160372 | Underway, recruiting completed | Baxter Healthcare | Recombinant Human Coagulation Factor Ⅷ for Injection (trade name: Advate) | Hemophilia | To assess the safety and tolerance of Advate in treating moderate to severe hemophilia A Chinese patients previously untreated, including the inhibitor formation, and other severe and non-severe adverse events |
CTR20160410 | Underway, having not recruited | Sinocelltech | SCT800 | Hemophilia A | To assess the efficacy of SCT800’s on-demand treatments of bleeding of hemophilia A patients |
CTR20150272 | Underway, recruiting | Wyeth | Recombinant Human Coagulation Factor Ⅷ for Injection | Hemophilia A | To assess the important medical event (FVHI inhibitor formation) following hemophilia A subjects’ receiving of Xyntha under the conventional treatment environment in China |
(Source: CDE, company announcements)
Related news:
The theoretical market size of coagulation factor Ⅷ exceeds RMB10 billion in China
About the Author:
Caicai, a Master of Pharmacy from Shanghai Jiaotong University, used to work in the Institute of Science and Technical Information. Currently as a practitioner in the drug surveillance system, she is good at interpreting industry regulations, pharmaceutical research developments, etc.
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