November 17, 2022
Hemophilia A is a genetic disorder quite prevalent across the globe affecting almost every patient population globally. Based on severity, hemophilia A can be classified into three stages: severe (<1% of FVIII in the blood), moderate (1–5% of FVIII in the blood), or mild (6–49% of FVIII in the blood. There are three main categories to treat hemophilia: factor replacement therapy (the missing factor is replaced synthetically for the patient), desmopressin acetate therapy (uses a nasal spray or tablet to boost factor VIII levels to reduce bleeding incidents), and gene therapy. Although emerging treatment regimens have shifted their focus to gene therapies, the road to a cure still faces obstacles.
The incidence of hemophilia A is 1 in 10,000 live births or 1 in 5,000 male births. The prevalence of hemophilia A is nonuniform in the MENA region; the most occurrences being in the capital regions and low occurrences in countries like Bahrain. The Centre of Arab Genomic Studies (CAGS) indicated that hemophilia is not a very common disease in Bahrain.
In 2016, the Kingdom of Saudi Arabia (KSA) reported 334 hemophilia A cases. Among these, the number of prevalent and incident cases of hemophilia A with clinically identified inhibitors were 48 and 4, respectively.
Drug Approvals in MENA region
In the MENA region, several therapies have been approved by the regulatory authorities of the respective countries. Recombinant FVIII class, HEMLIBRA – bispecific factor IXa- and factor X-directed antibody, is expected to take a major share in the markets, and impact is expected to be more pronounced in products with a short half-life. Hemlibra is approved in almost all of the MENA countries. The reason behind this is a strong performance in the clinical trials and an advantageous one-week dosing schedule. Because of its extended half-life, the patient switch is even more. Also, one cannot oversee the subcutaneous route of administration which makes it a great success in this segment of high unmet needs. It is the only approved medicine for all people with hemophilia A, with or without factor VIII inhibitors, and is approved in more than 100 countries, including all of the MENA region.
In May 2017, Sobi announced that the Saudi Food and Drug Authority (SFDA) in the Kingdom of Saudi Arabia has approved Elocta (efmoroctocog alfa), a recombinant human factor VIII Fc-fusion protein with an extended half-life, for the treatment of hemophilia A. Elocta was the first extended half-life and recombinant factor VIII Fc fusion protein therapy approved for the treatment of hemophilia A in Saudi Arabia, previously approved in Kuwait in 2016. In June 2022, Esperoct was approved in Saudi Arabia as well.
“We will now focus on ensuring access to Elocta for people living with hemophilia A across other Middle Eastern states. This is a very important milestone to ensure that patients with hemophilia A have early and sustainable access to this bleed prevention treatment.”
─ Ebrahim Al-Hagiri, Regulatory & Patient Access Manager Middle East & Turkey, Sobi
The number of Hemophilia drugs that are approved in the region has increased. There are more than 10 drugs approved in Saudi Arabia, 13 in UAE, 9 in Qatar, 8 in Israel, and approximately 5 in Kuwait. The most common approvals in the region are Hemlibra, Novoseven, Novoeight etc. The other drugs approved in the region include Advate, Xyntha, Afstyla, Wilate, Feiba, Kovaltry etc.
Quick update on emerging therapies
Few countries in the MENA region are evaluating RNAi-based therapies, gene therapies, recombinant fusion protein, and others. Israel, Algeria, and Dubai have a robust pipeline with novel gene therapies sponsored by big players such as Sanofi, Novo Nordisk etc. Other key players in the MENA region include Sobi, Pfizer, Spark Therapeutics, CSL Behring, Biomarin, and others.
- The AFFINE study by Pfizer is also ongoing in Riyadh Dubai, which is one of the most anticipated trials for hemophilia A after the clinical hold upliftment in March 2022.
- Israel’s Sheba Medical Center has been chosen by American biotechnology company BioMarin to conduct clinical trials and research on a breakthrough gene therapy product related to hemophilia.
- BioMarin is currently evaluating Valrox for hemophilia A.
- Fitusiran, a Sanofi’s asset for hemophilia A is also being studied in US and Israel in the MENA region.
- Concizumab, a highly anticipated tissue factor protein by Novo Nordisk, is also being studied in Algeria, apart from the 7MM market.
- Spark Therapeutics, a subsidiary of Genentech, is also conducting a trial for SPK-8011 in Israel.
- Mim8, another lead candidate of Novo Nordisk, is under development in Saudi Arabia.
- In Tunisia, the trial for Kogenate is ongoing, while Lebanon has completed trials for CSL627.
Cost burden – A major downfall in treatment
- The high cost of hemophilia A drug is a major barrier to accessibility for treatment. According to a study by Malhan et al. (2020), the most important reason hemophilia A has a significant economic burden in Turkey is the expensive cost of replacement therapy. The major cost contributor was identified as factor replacement therapy, and with inhibitor development, the average annual cost increased more than threefold. The high cost of standard half-life drugs is also a challenge in developed countries, including the MENA region. One possible reason could be progressive clotting factors used to prevent bleeding episodes, not just to treat them, increasing patients’ dependency on treatment and surging the need for these therapies to manage the disease.
- The cost of 1 mL vial of Hemlibra (150 mg/mL) is approximately USD 14,800 in the UAE and USD 13,900 in the Kingdom of Saudi Arabia, as per the Ministry of Health, which is lower than the price in the US (USD 16,600) but still very high.
Stronghold of hemlibra
- The monopoly of already approved therapies, such as HEMLIBRA and ELOCTA, which have successfully achieved a milestone giving tough competition to the new drugs in the pipeline, further reduces the upcoming R&D in the MENA region. Also, the introduction of HEMLIBRA led to reductions in the overall drug cost and administration costs due to the reduced need for on-demand administrations, increasing the chunk of patients to switch to this therapy instead.
The community’s social integration and economic well-being are significantly impacted by hemophilia as a disease and its management. The inability to participate fully in society and the high cost of medical care make this illness a severe issue for all hemophiliac sufferers. Desmopressin (DDAVP) or antifibrinolytics may treat persons with mild hemophilia A. However, extended half-life medicines and more cutting-edge methods like siRNA, bi-specific antibodies, and gene therapy are expected to continue to dominate the field of hemophilia treatment. Since AAV vector-based gene therapy is thought to be the first curative treatment option for this bleeding illness, expectations are high. It should be underlined that adequate financing and strategic alliances are essential throughout the MENA area to offer a platform to support real advances in gene therapy R&D.
Source: Delveinsight – www.delveinsight.com