DDW Editor Reece Armstrong speaks to Stephanie Seremetis, Chief Medical Officer, Rare Blood Disorders at Novo Nordisk to get her response to the company’s latest study results for its Mim8 antibody.
Earlier this year, pharmaceutical company Novo Nordisk announced positive results from Phase I & II clinical trials investigating its antibody treatment for haemophilia A.
Novo Nordisk’s Mim8 treatment is a next-generation human IgG4 bispecific antibody bridging Factor IXa/X (FIXa/FX) designed as a once-a-week or once monthly treatment for haemophilia A with or without inhibitors. The antibody brings FIXa and FX together thereby replacing missing FVIII, which in turn stimulates production of thrombin that helps blood to clot.
The company has been investigating Mim8 in its Phase I & II FRONTIER1 study and recently reported positive interim results from the study at the International Society of Thrombosis and Haemostasis Annual Congress (ISTH 2022) in London, UK.
Interim results presented by Novo Nordisk show that Mim8, given in a once-weekly and once-monthly dose, was able to reduce bleeds in haemophilia A patients. Those data, whilst only accounting for 32 patients, did show that six of seven participants in the lowest dose cohort still reported at least one bleed, whereas at high doses, only two of the 25 patients reported bleeds. Zero bleeds were reported in the eight participants treated with the therapy once monthly.
RA: How pleased are you with the interim results of the Frontier Study?
SS: The data of FRONTIER1 are encouraging and present an opportunity to develop a treatment for people with haemophilia A who may benefit from less frequent administration1,2. We look forward to moving into phase 3 clinical development, which is due to commence in Q4 2022.3
RA: Could you discuss how Mim8 works as a therapy and its benefits to patients (less frequent dosing etc.)
SS: Mim8 is a next-generation human IgG4 bispecific antibody for treatment of haemophilia A regardless of inhibitor status. Administered via subcutaneous injection (under the skin), it is designed as prophylaxis treatment (to prevent bleeds) in people living with haemophilia A who may benefit from less frequent (once-weekly or once-monthly) treatment administration.
Mim8 works by mimicking activated Factor VIII (FVIII). It bridges Factors IXa and X (FIXa/X) and acts as a potent co-factor to FIXa. This leads to Factor X (FX) activation and subsequent thrombin generation, which helps blood to clot.4 Mim8 has been optimised to have a stimulatory effect on FIXa activity, enabling FX activation, while still maintaining a low binding affinity to FIX/FX to reduce the risk of systemic coagulation. This enables low-volume administration for once-monthly and once-weekly dosing.
The individual, complex and changing needs of people living with haemophilia means there is no ‘one-size-fits-all’ in its treatment. For people living with haemophilia and the medical community, it is important to allow for fully personalised care, which includes offering different treatment options that directly address each changing and individual need. This ensures all people living with haemophilia receive appropriate care throughout their life.
RA: How does Mim8 compare to current treatments for Haemophilia A such as replacement therapy?
SS: Mim8 is being developed as a subcutaneous option with less frequent administration, rather than intravenous administration that is required for Standard of Care FVIII concentrates. Although no comparative data are available yet, phase III will include comparison of Mim8 to Standard of Care.
RA: The Frontier programme is using an accelerated time to expedite the time from Phase II to Phase III. Could you elaborate on this?
SS: In FRONTIER1, phase I and phase II was combined into a single clinical trial, thereby expediting the study time. As well, recruitment of patients into phase III has started.
RA: What are the challenges of conducting a rare disease trial for haemophilia in relation to its patient base?
SS: Doing clinical research and development in any rare disease including haemophilia is very different from diseases with a larger population, such as diabetes. The design of the clinical development program must strike the balance of being able to recruit the needed number of participants that will meet health authority requirements and address the endpoints that will enable regulatory approval, as well providing access to people living the disease globally.
RA: Novo Nordisk recently announced positive results for its concizumab treatment. How do both treatments represent Novo Nordisk’s approach to rare diseases and haemophilia A/B?
SS: Novo Nordisk remains committed to transforming the lives of people with haemophilia. We are building on our 30+ year heritage in haemophilia with a broad portfolio and pipeline, expanding the indications of our products to benefit even more people, and developing integrated therapeutic solutions. This approach allows the potential for personalised care to help people with haemophilia live life beyond their bleeding disorder.
1 ClinicalTrials.gov. A Research Study Investigating Mim8 in People With Haemophilia A (FRONTIER1) (NCT04204408). Available at: https://clinicaltrials.gov/ct2/show/NCT04204408. Accessed: July 2022.
2 Chowdary P, Lopez-Jaime FJ, Mahlangu J, et al. FRONTIER1: A Phase 1/2 Dose Escalation Study of a Novel Factor VIIIa Mimetic Bispecific Antibody, Mim8, for Evaluation of Safety, Pharmacokinetics, and Efficacy. Abstract presented at International Society of Thrombosis and Haemostasis (ISTH) 2022.
3 Windyga J, Chowdary P, Lopez-Jaime F, et al. Mim8 is associated with improved thrombin generation vs. emicizumab in patients with haemophilia A, with and without inhibitors. Abstract presented at International Society of Thrombosis and Haemostasis (ISTH) 2022.
4 Østergaard H, Lund J, Greisen PJ, et al. A factor VIIIa-mimetic bispecific antibody, Mim8, ameliorates bleeding upon severe vascular challenge in hemophilia A mice. Blood. 2021;138(14):1258-1268. doi:10.1182/blood.2020010331