Oxcia also receives ODD approval from EMA

Oxcias leading drug candidate OXC-101 is a so-called “first-in-class” mitotic MTH1 inhibitor. It has a dual mechanism of action that allows it to target a weakness of cancer cells – their high levels of oxidative stress and their propensity to develop DNA damage. In short, OXC-101 induces additional oxidative stress and prevents the cancer cells from repairing the DNA damage.

Preclinical studies have shown that OXC-101 significantly reduces tumor growth and prolongs survival in acute myeloid leukemia (AML) models, and further development is supported by clinical results from a Phase I study in patients with advanced hematological cancers.

Oxcia is currently conducting an expansion study, a combined phase I/II study, in a selected patient population with relapsed/recurrent AML. The treatment is given in combination with idarubicin, one of the established standard treatments in the field. The aim of the study is to confirm the promising preliminary effects previously observed, and to lay the foundation for a pivotal phase II study that could in turn form the basis for regulatory accelerated approval.

Orphan Drug Designation from both EMA and FDA

Oxcia recently announced that OXC-101 has been granted Orphan Drug Designation (ODD) by the European Medicines Agency (EMA). This provides several key benefits during the development process, including regulatory support, reduced fees and 10 years of market exclusivity in the EU following approval.

OXC-101 has previously also received ODD from the US FDA, which provides similar benefits and 7 years of market exclusivity in the US market.

CEO comments on the double approval

BioStock contacted Oxcia's CEO Ulrika Warpman Berglund to learn more about the significance of granted orphan drug status in both the US and Europe.

How does the EMA's ODD approval, together with the FDA's ODD for OXC-101, strengthen your position in AML treatment?

– That our drug candidate OXC-101 against AML has now received ODD from both the FDA and EMA is a clear recognition of its potential to meet a critical medical need and strengthens Oxcia's position in several crucial ways.

– These dual approvals provide us with up to 10 years of market exclusivity in the EU and 7 years in the US, accelerated regulatory processes and significant cost savings. The EMA approval also provides support and scientific advice from the EMA's Committee for Orphan Medicinal Products (COMP) for orphan drugs and strengthened credibility in the EU and US drug development environments.

– That is, having ODD from both the FDA and EMA signals that both authorities believe that OXC-101 has scientific potential to treat a rare and serious disease. The EMA also evaluates whether the drug candidate can offer significant benefit compared to existing treatments. This strengthens Oxcia's OXC-101 scientific credibility and differentiation from competitors.

Could you tell us a little more about the benefits of ODD in both the US and the EU?

– Regulatory support from two of the world's largest pharmaceutical authorities, and a lower commercial risk thanks to exclusivity periods and incentives are significant advantages. This facilitates the work of obtaining additional venture capital and licensing agreements with pharmaceutical companies.

– It can also enable parallel development and launch in two of the world's largest pharmaceutical markets and facilitate the streamlining and harmonization of clinical trials and regulatory processes.

What can you tell us about the preclinical or clinical data that forms the basis for the ODD application?

– Treatment with OXC-101 significantly increases survival in several different preclinical disease models. OXC-101 can kill AML cancer cell lines as well as primary AML cancer cells and their stem cells taken from bone marrow of AML patients. We also have preclinical data that support the proposed unique mechanism of action of OXC-101, which is a so-called mitotic MTH1 inhibitor. In addition to OXC-101 having potential as a monotherapy with better efficacy than cytarabine (which is one of the standard treatments for AML) in AML disease models, we also see that OXC-101 can further improve the efficacy of treatment with different standard combinations (different chemotherapies). We have previously published several of these preclinical data in peer-reviewed scientific journals (Sanjiv et al., Cancer Res. 2021 Nov 15;81(22):5733-5744. doi: 10.1158/0008-5472.CAN-21-0061; Centio et al., Mol Cancer Ther (2022) 21 (5): 703–714. doi: 10.1158/1535-7163.MCT-21-0185).

– The clinical data is limited so far as the MAATEO study, a clinical phase I/II with an expansion group of relapsed/refractory AML patients, is still ongoing. These patients are severely ill and no longer respond to previous treatments. They may therefore be offered to participate in clinical trials or palliative care as the only remaining option. In several of these patients, we have seen clinical benefits with a partial response and some stable disease up to 5 months, which is a long time for this aggressive disease in this phase. Some improvement in quality of life has also been reported.

– In collaboration with Dr. Tom Erkers and Nona Struyf, Scilifelab/Karolinska Institutet, we are performing so-called precision medicine studies on bone marrow samples from patients in the MAATEO study. Here we have started to see a very exciting trend of responses with OXC-101 treatment, while standard treatments have failed to affect/kill AML cells from the patients' bone marrow samples. This indicates a potential clinical benefit with OXC-101. Oxcia, together with Dr. Erkers, Dr. Stefan Deneberg, Karolinska University Hospital and Dr. Bertil Uggla, Örebro University Hospital, has an ongoing Vinnova grant for the MAATEO study.

Will the ODD decision affect the design or priorities in the clinical development of OXC-101? 

– Today, we have ongoing clinical studies in Europe and a good network. The ODD announcement from the EMA increases interest in OXC-101 even more, which facilitates future studies and contacts with various partners. The ODD classification from the FDA that we received in February this year strengthens the possibilities of also conducting studies in the USA in the relatively near future. Thanks to the FDA's ODD approval, Oxcia has established contact with a leading AML clinic, MD Andersson, in the USA.

– The USA is currently the dominant market in terms of size and accounts for approximately 2/3 of the market for the 8 largest markets (Global data 2023). Oxcia prioritizes both the USA and the European markets and takes other interesting markets as a next step.

How do you plan to utilize the ODD benefits to accelerate/facilitate the development of OXC-101? 

– As a first step, we will ensure that we use the advice offered as soon as possible to ensure that we plan the studies in the best and most efficient way, so that we have the greatest opportunity to show good effect but also optimize time and costs. Discussions with potential partners are also facilitated by the potentially faster path to approval, market exclusivity and the review from the EMA which indicates that OXC-101 can offer significant benefit compared to existing treatments.

What are the prospects for ODD for your second candidate, OXC-201?

– OXC-201 is being developed as a new potential treatment for idiopathic pulmonary fibrosis, also a rare and serious disease with a great medical need. As OXC-201 is in the preclinical phase, we plan to submit an ODD application to the FDA, which does not require clinical data. Our preclinical data with OXC-201 in IPF looks very exciting and promising. Not least with our latest data where we see that, in addition to affecting biomarkers for inflammation and fibrosis, we can improve lung function in preclinical disease models. We are confident about the possibilities of obtaining ODD from the FDA for OXC-201 in IPF. We also plan to apply for ODD from the EMA when clinical data are available.