Date: 2018-10-04
Type of information: Granting of a Market Authorisation in the US
Product name: Hemlibra®
Compound: emicizumab (ACE910 - anti-factor IXa x anti-factor X humanized bispecific antibody)
Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases
Action mechanism:
- bispecific antibody. Emicizumab is a bispecific antibody that works by mimicking the coagulation function of factor VIII.
- Emicizumab was designated as a Breakthrough Therapy by the FDA in September 2015.
Company: Chugai Pharmaceutical (Japan) Roche (Switzerland)
Disease: hemophilia A without factor VIII inhibitors
Latest news:
- • On October 4, 2018, Roche announced that the FDA has approved Hemlibra® (emicizumab-kxwh) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children, ages newborn and older, with haemophilia A without factor VIII inhibitors. Hemlibra® is now the only prophylactic treatment for people with haemophilia A with and without factor VIII inhibitors that can be administered subcutaneously and at multiple dosing options (once weekly, every two weeks or every four weeks). This approval is based on positive results from the phase III HAVEN 3 and HAVEN 4 studies. Hemlibra prophylaxis led to statistically significant and clinically meaningful reductions in treated bleeds compared to no prophylaxis (primary endpoint) and across all other bleed-related endpoints in the HAVEN 3 study, and showed a clinically meaningful control of bleeding in the HAVEN 4 study.
- In the phase III HAVEN 3 study, adults and adolescents aged 12 years or older with haemophilia A without factor VIII inhibitors who received Hemlibra prophylaxis once weekly (n=36) or every two weeks (n=35) experienced a 96% (95% CI: 92.5; 98.0, p<0.0001) and 97% (95% CI: 93.4; 98.3, p<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis (n=18). Hemlibra is the first medicine to significantly reduce treated bleeds compared to prior factor VIII prophylaxis, which has been the recommended standard of care, as demonstrated by a statistically significant reduction of 68% (95% CI: 48.6; 80.5, p<0.0001) in treated bleeds in a prospective intra-patient comparison (n=48) of people who previously received factor VIII prophylaxis in a non-interventional study and switched to Hemlibra prophylaxis. In the single-arm phase III HAVEN 4 study of adults and adolescents aged 12 years or older with haemophilia A with factor VIII inhibitors (n=5) and without factor VIII inhibitors (n=36), Hemlibra prophylaxis every four weeks (n=41) led to clinically meaningful control of bleeding. The most common adverse reactions occurring in 10% or more of people treated with Hemlibra in pooled studies (n=391) were injection site reactions (n=85), headache (n=57) and joint pain (arthralgia; n=59).
- In the HAVEN 4 study, 56.1% (95% CI: 39.7; 71.5) of people with or without factor VIII inhibitors treated with Hemlibra prophylaxis every four weeks experienced zero treated bleeds and 90.2% (95% CI: 76.9; 97.3) experienced three or fewer treated bleeds.
- • On June 5, 2018, Roche announced that the FDA has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Hemlibra® (emicizumab-kxwh) for adults and children with haemophilia A without factor VIII inhibitors. The sBLA is based on data from the phase III HAVEN 3 study.
- In the HAVEN 3 study, adults and adolescents aged 12 years or older with haemophilia A without factor VIII inhibitors who received Hemlibra prophylaxis every week or every two weeks showed a 96% (p<0.0001) and 97% (p<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis. In an additional arm of the study, people who had previously received factor VIII prophylaxis in a non-interventional study switched to Hemlibra prophylaxis, allowing for an intra-patient comparison of two prophylaxis regimens. Based on the intra-patient comparison, Hemlibra demonstrated a statistically significant reduction of 68% (p<0.0001) in treated bleeds, making it the first medicine to show superior efficacy to prior treatment with factor VIII prophylaxis, the standard of care. There were no unexpected or serious adverse events (AEs) related to Hemlibra in the HAVEN 3 study, and the most common AEs were consistent with previous studies. The most common AEs occurring in 5% or more of people in the HAVEN 3 study were injection site reactions, joint pain (arthralgia), common cold symptoms (nasopharyngitis), headache, upper respiratory tract infection and influenza. Results from the HAVEN 3 study were presented at the World Federation of Hemophilia (WFH) 2018 World Congress in May.
- The FDA granted Breakthrough Therapy Designation for Hemlibra in people with haemophilia A without factor VIII inhibitors in April 2018 based on data from the HAVEN 3 study. The FDA is expected to make a decision on approval by 4 October 2018.
- Data from the HAVEN 3 study have also been submitted for approval consideration to the European Medicines Agency. Submissions with other regulatory authorities around the world are ongoing.
- Hemlibra™ was approved by the FDA in November 2017 for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with haemophilia A with factor VIII inhibitors based on results from the HAVEN 1 and HAVEN 2 studies. Hemlibra was also recently approved by regulatory authorities in other countries around the world, including by the European Commission in February 2018 for routine prophylaxis of bleeding episodes in people with haemophilia A with factor VIII inhibitors.
- • On April 26, 2018, Chugai Pharmaceutical announced today that it filed applications for its anti-coagulation factor IXa/X humanized bispecific monoclonal antibody / coagulation factor VIII substitute, Hemlibra® Subcutaneous Injection 30 mg, 60 mg, 90 mg, 105 mg, and 150 mg” to the Ministry of Health, Labour and Welfare (MHLW) for an additional indication of prophylactic treatment for people with hemophilia A without inhibitors to factor VIII, as well as for additional dosage and administration as a biweekly or every four-week treatment for people with hemophilia A with inhibitors to factor VIII. These filings are based on the results from HAVEN 3 study (NCT02847637) and HAVEN 4 study (NCT03020160). HAVEN 3 study is a global phase III study evaluating HEMLIBRA subcutaneous injection, once a week and once every two weeks, in people with hemophilia A (12 years of age or older) without inhibitors to factor VIII. HAVEN 4 study is a global phase III study evaluating efficacy, safety, and pharmacokinetics of HEMLIBRA subcutaneous injection every four weeks in people with hemophilia A (12 years of age or older), with and without inhibitors to factor VIII. Based on the results from these studies, the filings were submitted for two purposes including: 1) expansion of the indication to include weekly, biweekly, or every four-week subcutaneous treatment for people with hemophilia A without inhibitors to factor VIII; and 2) addition of dosage and administration to include the biweekly or every four-week subcutaneous treatment for people with hemophilia A with inhibitors to factor VIII for whom the weekly injection has previously been approved.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2018-10-04
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
