Delving into the Latest Updates on Nonacog alfa with Synapse

Overview

Basic Info

Drug Type

Recombinant coagulation factor

Synonyms

Benefix, Benefix Rts, Blood-coagulation-factor-IX-synthetic-human, Factor-IX-Genetics-Institute

+ [10]

Target

F8

Mechanism

F8 stimulants(Coagulation factor VIII stimulants), Blood coagulation pathway activation

Therapeutic Areas

Congenital DisordersHemic and Lymphatic DiseasesOther Diseases

Active Indication

Hemophilia B

Inactive Indication-

Originator Organization

Pfizer Inc.

Active Organization

Pfizer Europe MA EEIGWyeth Pharmaceuticals LLC

Haleon (Suzhou) Pharmaceutical Co. Ltd.

+ [1]

Inactive Organization

Pfizer Inc.Wyeth AB

Drug Highest PhaseApproved

First Approval Date

US (11 Feb 1997),

Hemophilia B

RegulationOrphan Drug (JP), Special Review Project (CN)

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Gene Sequence

Sequence Code 23878

In hemophilia, deficiency of factor VIII or IX prevents the activation of the common coagulation pathway, and inhibits the conversion of FX to activated FXa, which is required for thrombin generation. We hypothesized that the direct expressed FXa has the potential to activate the common pathway and restore coagulation in hemophilia patients. In this study, the cassettes that expressed FXa, FXaop and FXa-FVII were packaged into an engineered AAV capsid, AAV843, and were delivered into hemophilia A and B mice by intravenous injection. AAV-FXaop could be stably expressed in vivo and showed the best immediate and prolonged hemostatic effects, similar to those of commercial drugs (Xyntha and Benefix). AAV-FXaop also significantly inhibited bleeding in hemophilia A mice with inhibitors. In addition, FXa expression in joints significantly alleviated the occurrence of hemophilic synovitis. AAV-delivered FXa may be a novel target for treating hemophilic and hemophilic synovitis.

01 Feb 2024·Journal of Chromatography A

Advances and challenges in the purification of recombinant coagulation factors: A review

Review

Author: Yu, Linling ; Sun, Yan ; Chu, Mengyao ; Yang, Dongmei

Hemostasis is a complex process for the cessation of bleeding from an injured blood vessel, involving the interplay of 12 coagulation factors in the coagulation cascade with activated blood platelets and the vessel wall. Hence, the coagulation factors are important to control hemorrhage. However, the low abundance of many coagulation factors in human plasma proteins limited their production in therapeutic drugs and their clinical applications. With the development of modern biotechnology, commercially manufactured recombinant coagulation factors became available as hemostatic therapeutics, emerging a huge potential in pharmaceutical manufacturing market. Unlike antibodies, whose standard operation unit or platform purification processes in the industrial-scale downstream processing has been well-established, the complexity in post-translational modification and differences in structures of the coagulation factors posed specific challenges with respect to the downstream processing, which have long been limiting their industrial-scale production. This review presents a comprehensive overview of the technological development of commercially manufactured recombinant coagulation factors, with emphasis on their advances and challenges in the separation and purification processes. Firstly, the licensed products of the plasma derived and recombinant coagulation factors are summarized. Then, typical recombinant coagulation factors, i.e. factors VII, VIII and IX, are introduced with detailed discussion on their preparative separation procedures for both the licensed products of industrial-scale and the experimental cases of laboratory-scale. Finally, perspectives and challenges in the future development of the purification technology of recombinant coagulation factors are highlighted to provide new insight into the design of cost-effective purification processes of recombinant coagulation factors.

01 Oct 2023·Indian Journal of Hematology and Blood Transfusion

Nonacog Alfa for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Patients with Moderately Severe or Severe Hemophilia B in India

Article

Author: Rangarajan, Savita ; Gupta, Pritam ; Ramakanth, G S H ; Rupon, Jeremy ; Chand, Rohit ; Muley, Hitesh Bhaskarrao ; Pai, Seema ; Choraria, Nirmalkumar ; John, M Joseph ; Apte, Shashikant ; Parvatini, Shyam ; Simoneau, Damien ; Chhabra, Amit

AbstractPurposeHemophilia B is an X-linked congenital bleeding disorder caused by a deficiency of coagulation factor IX (FIX) clotting activity. This study evaluated safety and efficacy of nonacog alfa, a recombinant human blood coagulation FIX replacement product, in males aged 12–65 years with hemophilia B (FIX activity ≤ 2%) with or without inhibitors in India.MethodsIn this multicenter, open-label, post-approval phase 4 study, participants were treated for up to 8 weeks, with up to a 4-week screening period and a subsequent post-treatment 28-day safety observation period. Intravenous nonacog alfa 40 IU/kg (range 13–78 IU/kg) was administered at intervals of 3–4 days, in accordance with the approved local product document.ResultsA total of 25 participants were enrolled and completed the study. No participants developed FIX inhibitors during the study, experienced treatment-related adverse events (AEs) or serious AEs, or developed a thrombotic event and/or hypersensitivity reaction. No participants experienced bleeding events requiring on-demand treatment with nonacog alfa. Seventeen bleeding episodes (16 spontaneous and 1 traumatic) were reported in 10 participants; all occurred post treatment, with the exception of a minor gum-bleeding event, and were managed without treatment. The mean (SD) annualized total factor consumption (TFC) per patient was 224,582 (75,527) IU; the mean (SD) annualized TFC by weight per patient was 3639 (573) IU/kg.ConclusionNonacog alfa was safe and effective for the prevention of hemorrhagic episodes in Indian males with congenital, severe hemophilia B. No participants developed FIX inhibitors, and no new safety signals were reported.

100 Deals associated with Nonacog alfa

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	B02BD04	DB00100

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hemophilia B	US	Wyeth Pharmaceuticals LLC	11 Feb 1997

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hemophilia B	Discovery	-	Wyeth AB	07 Oct 2004

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02336178 (Pubmed \| Medicine (Baltimore)) Manual	Phase 4	Hemophilia B	70	Nonacog Alfa	(jsmnkezrng) = rrwirpyhao etgeserxou (tvblziitgd, 0 - 7.7) View more	Positive	28 May 2021
NCT03186677 (CTgov)	Phase 1	Hemophilia B	11	BeneFIX+ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg (Cohort 1)	tpmeiszvcz(lrtjomjjcj) = cgzlbqryjx kaeszsnnog (dwhljzmnqo, zicdocxpxv - zgmtcvtbht) View more	-	10 Nov 2020
NCT03186677 (CTgov)	Phase 1	Hemophilia B	11	ISU304/CB2679d/Dalcinonacog alfa 75~150 IU/kg (Cohort 2)	tpmeiszvcz(lrtjomjjcj) = kqjmgnymno kaeszsnnog (dwhljzmnqo, vergdabepj - ycqeigtvkd) View more	-	10 Nov 2020
NCT03091751 (CTgov)	Phase 2	Hemophilia B	13	BeneFIX	ldwrgibceo(zpdbsunwhi) = rmgqrleyqc cwdsxpzbll (hnmnmfradi, xwsazkmfvo - xlqkzlhzvj) View more	-	25 Jul 2017
NCT02336178 (CTgov)	Phase 4	Hemophilia B	70	Benefix	jhhriwxokm(alitaynrtz) = puummriszf bjafszscoq (oetkdxkmpe, kufuxqarmd - yjitiarjhs) View more	-	04 May 2017
NCT02213250 (CTgov)	Phase 1	Hemophilia B	12	BeneFIX (BeneFIX 50 IU/kg; >=6 and <12 Years)	uvbshrkegm(tyfdgpxomb) = gremzgpjvi biifyeqtwa (kncyiabdfw, tzbgqgcqju - epxacsbifg) View more	-	25 Jul 2016
NCT02213250 (CTgov)	Phase 1	Hemophilia B	12	BeneFIX (BeneFIX 50 IU/kg; Age Group:>=12 Years)	uvbshrkegm(tyfdgpxomb) = xgjktbvnwh biifyeqtwa (kncyiabdfw, mkffecubux - iuvifwiucu) View more	-	25 Jul 2016
NCT00037557 \| NCT00093171 \| NCT00093210 \| NCT00167973 \| NCT00364182 (Pubmed \| Blood Coagul Fibrinolysis)	Phase 3	Hemophilia B	412	Nonacog alfa	cmpjuyhvwh(idxgxptvyj) = FIX inhibition (n = 5) lkfgrfrrsn (uupxsfnqrg ) View more	-	01 Dec 2015
NCT00364182 (CTgov)	Phase 3	Hemophilia B	50	BeneFIX (BeneFIX OD1)	qenokdhtjr(ikjwkpdjyg) = nczevfukym ytnyjeacvq (geaorozkyn, bhjvhofcms - zkimcmyupo) View more	-	23 Aug 2011
NCT00364182 (CTgov)	Phase 3	Hemophilia B	50	BeneFIX (BeneFIX 100 IU/kg)	qenokdhtjr(ikjwkpdjyg) = jhipbrfomv ytnyjeacvq (geaorozkyn, wfinhihjhs - eksolmlqtr) View more	-	23 Aug 2011
NCT00866606 (CTgov)	Phase 3	Hemophilia B	35	BeneFIX	xtnwzwzzrg(wecjutnbpm) = awjzthohrc jqlmebdfrb (phrnnoyvws, gltympwbyu - okahobznhk) View more	-	04 Jan 2011
NCT00749476 (CTgov)	Phase 4	Hemophilia B	1	BeneFIX	kduwtmzpuw(vzhocveuab) = jovqaqeeej weibrrqgkh (otlbokmwso, irxnpakieq - hynmfnireq) View more	-	29 Jun 2010