Trenonacog alfa




New Medicines

IXinityHaemophilia B


New molecular entity
Emergent BioSolutions
Emergent BioSolutions

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
01. Aug 11: filing planned in the EU by the end of 2011 [1].
02. Sep 11: EU MAA accepted for IB 1001 in the treatment and prevention of bleeding in individuals with haemophilia B [2].
03. Apr 12: Filed in the US [3].
04. Jun 13: Cangene has withdrawn its EU filing but intends to refile for marketing approval with the additional clinical data requested by the EMA. The company is also addressing issues raised by the FDA in a Complete Response Letter in Feb 13. The FDA ha asked for additional manufacturing and development information but no additional clinical data [7].
05. Q1 14: Emergent BioSolutions commences advanced preparations for the potential launch of trenonacog alfa following acquisition of Cangene, upon FDA approval [9].
06. Mar 15: Listed as PIII in Emergent pipeline [11].
07. Apr 15: US FDA approved IXINITY® for control and prevention of bleeding episodes and for perioperative management in adults and children with Haemophilia B [12].
08. Aug 15. Launched in US [13].
09. Jan 18: No recent reports of EU devlopment
10. Aug 18, United Therapeutics reported that the phase III FREEDOM-EV trial had met its primary endpoint (Time to first clinical worsening event) and they planned to submit the results to the FDA in support of a label amendment. The company is also evaluating whether the results could support marketing applications outside the US. [16]


A recombinant factor IX based on patent-protected, recombinant protein manufacturing technologies aimed at significantly increasing cell-line productivity
31 August 2011Haemophilia B is caused by factor IX deficiency and occurs in ~1 out of every 30,000 male births. About 60% of people with haemophilia have a severe condition, which results in frequent spontaneous bleeding episodes [1].
Haemophilia B

Trial or other data

01. IB1001, an IV recombinant factor IX (FIX) product, being developed for the treatment and prevention of bleeding in individuals with haemophilia B, is in Phase III clinical testing, in an ongoing study in Europe, the US, Israel and India [1].
02. Aug 11: Ipsen and Inspiration Biopharmaceuticals have entered into a strategic partnership agreement to launch Inspiration´s haemophilia product portfolio in Europe [1].
03. Jul 12: The FDA has placed a clinical hold on clinical trials evaluating the safety and efficacy of IB1001 for the treatment and prevention of bleeding episodes in people with hemophilia B. This impacts two ongoing IB1001 clinical trials - a PIII study evaluating the safety and efficacy of IB1001 to treat and prevent bleeding episodes in adults with hemophilia B, and a PIII/b study evaluating the safety and efficacy of IB1001 to treat and prevent bleeding episodes in previously treated pediatric subjects with hemophilia B [4].
04. July 12: Trials were put on hold because a trend towards a higher proportion of pts treated with IB1001 developing a positive response to testing of antibodies to Chinese Hamster Ovary (CHO) protein, the product´s host cell protein, was seen. Small amounts of host cell protein are expected and documented in recombinant therapeutic products of all type, but the higher than expected rate of anti-CHO antibody development has led Inspiration to initiate a thorough investigation. A total of 86 people with hemophilia B have received IB1001 in clinical studies and, to date, no adverse events (anaphylaxis or other serious allergic type reaction and nephrotic syndrome) related to the development of antibodies to CHO protein have been reported. Furthermore, no relationship has been demonstrated between the development of antibodies to CHO protein and the development of any antibodies to factor IX. Inspiration continues to follow subjects enrolled in clinical trials of IB1001 to collect safety-related information and will share this information with regulators. [5]
05. Feb 13: Inspiration Biopharmaceuticals & Ipsen have sold worldwide rights to IB1001 (recombinant FIX) to Cangene [6].
06. Jul 13: The FDA has lifted the hold on clinical trials of IB1001, a recombinant Factor IX (rFIX). Cangene will now re-start ongoing studies and begin new studies to support licensing [8].
07. Jan 14: CanGene plans a PIII trial for Haemophilia B (in adolescents, in adults) in the USA and the United Kingdom (NCT02048111) [9].
08. Mar 15: No update available on progress of PIII NCT02048111 study [10].
09. Mar 15: PIII NCT02048111 study plans to enrol 18 pts in the EU & UK. Collection of primary outcome data (safety, pharmacokinetics and efficacy with respect to breakthrough bleeding and control of haemorrhaging) predicted to complete Oct 15 [10].
10. Apr 15: The approval of IXINITY is based on results from a Phase III, open-label, uncontrolled, multi-centre, global study evaluating safety, efficacy, and pharmacokinetics in previously treated adults and children 12 years of age or older with severe to moderately severe (factor IX level 50 exposure days and 45 received IXINITY for > 100 exposure days. The median duration of treatment on study was 16.2 months (range 2.4-39.6) for the routine treatment regimen and 14.1 months (range 2.3-36.9) for the on-demand treatment regimen. A total of 508 bleeding episodes were treated with IXINITY, of which 286 were in pts treated with the routine treatment regimen and 222 in the on-demand regimen. A majority of the bleeds, 84%, were resolved by one or two infusions of IXINITY. Haemostatic efficacy at resolution of a bleed was rated by the subjects as excellent or good in 84% of all treated bleeding episodes. In addition, administration of IXINITY resulted in haemostasis in study participants who underwent major surgical procedures. Fourteen adverse reactions were reported among 6 of the 77 subjects. The most common adverse drug reaction, observed in 2.6% of pts was headache. Other adverse reactions reported included asthenia (weakness), apathy (lack of feeling, emotion, interest, or concern), depression, dysgeusia (taste alteration), haemophilia, influenza (flu), injection site discomfort, lethargy (lack of energy) and skin rash. There were no reports of thrombotic events or allergic reactions [12].