Emicizumab

Novo is aiming to file for approval of Mim8 toward the end of 2024. Novo Nordisk has shared a closer look at phase 3 results on its hemophilia A candidate Mim8, revealing new data that show how it squares up against Roche’s blockbuster Hemlibra on key measures of efficacy and tolerability.  In May, Novo reported topline results from the study, which Jefferies analysts said “may near our ‘best’ case scenario, with convenient once-monthly dosing seeming similarly effective to once-weekly, and efficacy data that may challenge Roche's incumbent Hemlibra.” However, the initial readout lacked a look at annualized bleed rates (ABR), focusing instead on percentage changes, or injection site reactions. Novo filled in the gaps in the dataset in a presentation at the International Society of Thrombosis and Haemostasis Annual Congress over the weekend. The Danish drugmaker repeated the topline efficacy results and provided the rates of annualized bleeds and injection site reactions. In the trial population with no prior prophylaxis treatment, Novo estimated a mean ABR of 15.75 in the control group. The mean ABRs in the once-weekly and once-monthly Mim8 prophylaxis cohorts were 0.45 and 0.20, respectively.  In the trial population with prior coagulation factor prophylaxis, the mean ABRs in the once-weekly Mim8 prophylaxis cohort was 2.51, versus 4.83 on prior clotting factor prophylaxis. The once-monthly ABR was 1.78, compared to 3.10 on prior clotting factor prophylaxis. Trying to compare the results to Roche’s data throws up challenges. Roche brought Hemlibra to market on the strength of a phase 3 trial that enrolled people with Factor VIII inhibitors and ran another study in patients without inhibitors. Novo enrolled patients with and without inhibitors in its FRONTIER2 study. In patients without inhibitors previously treated with on-demand bypassing agents, Roche reported (PDF) an ABR of 2.9 in the Hemlibra group, versus 23.3 in the control cohort. The study of patients without inhibitors who had been receiving on-demand treatment reported annualized rates of bleeding events of 1.5 and 1.3 in the Hemlibra groups, compared to 38.2 in the control cohort. The rate of injection site reactions is an area where Hemlibra may be vulnerable. Jefferies analysts said in May the frequency of reactions must be less than 10% for a challenger to be clearly differentiated versus Hemlibra. Novo reported rates of 5.0%, 8.2%, 9.5% and 12.2% across four cohorts of patients treated with Mim8.  Novo is aiming to file for approval of Mim8 toward the end of 2024. In parallel, Roche is strengthening the defenses of Hemlibra, which brought in (PDF) 4.1 billion Swiss francs ($4.6 billion) last year. The Swiss drugmaker has launched two new vial options and is introducing a new administration kit as part of a push to make Hemlibra dosing more convenient.

Dive Brief:Novo Nordisk on Sunday disclosed detailed clinical trial results for an experimental hemophilia treatment dubbed Mim8, showing once-weekly and once-monthly doses of the antibody drug controlled bleeding in people with the more common A form of the disorder.The data, which were presented at the International Society on Thrombosis and Haemostasis Annual Congress in Thailand, fill in a positive picture for Mim8s effectiveness and safety. Novo had said in May that the Phase 3 trial, called Frontier-2, succeeded and shared topline findings.Among people who had not previously been on preventive treatment, researchers reported zero bleeds in 86% of study participants who received once-weekly Mim8, and 95% of those given the once-monthly dose. Those figures were 66% and 65%, respectively, among people in the trial who had prior preventive treatment.Dive Insight:The success of Ozempic and Wegovy, Novos drugs for diabetes and weight loss, have transformed the Danish drugmaker into the pharmaceutical industrys second largest. Not surprisingly, analysts and Wall Street investors are now laser focused on that portion of the companys business.But Novo continues to develop drugs for rare blood disorders, and has placed emphasis on the potential of Mim8. Its also invested in sickle cell disease, acquiring Forma Therapeutics two years ago and advancing another drug it licensed in 2018.The recent results for Mim8 are the first from a Phase 3 trial program that includes three other studies beyond Frontier-2.Novo enrolled 254 people with hemophilia A into Frontier-2, including those with and without inhibitors, which can prevent standard drugs from effectively clotting blood. The one-year study compared Mim8 to either no prophylaxis among those not on preventive treatment, or to prior coagulation factor prophylaxis among those who were.In the former group, a once-weekly dose of Mim8 reduced the average annualized bleeding rate by 97%, while the once-monthly dose led to a 99% reduction. That translated to an average of 0.45 treated bleeds per patient year among the once-weekly group and 0.20 among the once-monthly patients. In the control arm of people who did not receive preventive treatment, the average rate was 15.75 treated bleeds per patient year.Patients in the study who previously were on preventive treatment went through a run-in phase of the study, and then were given one of the two Mim8 doses. The average rate of treated bleeds was 2.51 per patient year for those on once-weekly dosing, versus 4.83 on their prior prophylaxis, and 1.78 for those on the once-monthly, versus 3.10 on their prior treatment.There were no thromboembolic events or related serious side effects reported in the trial, Novo said.With Mim8, we have the potential of offering a substantial proportion of patients the prospect of zero bleeds and convenient dosing flexibility to fit their lifestyles and needs, said Martin Holst Lange, head of development for Novo, in the companys Sunday statement.Novo plans to submit an approval application for Mim8 toward the end of the year, and will disclose more trial data for the drug at upcoming medical meetings.A bispecific antibody, Mim8 is designed to bridge Factors IXa and X to replace the Factor VIII thats missing in people with hemophilia A.If approved, Mim8 would likely compete with Roches Hemlibra, which is also a bispecific anitbody and holds approval in the U.S. as a routine preventive treatment for people with hemophilia A. Dosing is flexible to either once-weekly, bi-weekly or once-monthly. Roche reported sales of 4.1 billion Swiss francs last year, or about $4.6 billion, using an average U.S. dollar exchange rate for 2023. '