Apealea (“Paclical” in Russia and Kazakhstan) is a patented water-soluble formulation of XR17 and the API paclitaxel. Paclitaxel is one of the most widely used anti-cancer substances in the world and is included in the standard treatment of a variety of cancers such as lung cancer, breast cancer and ovarian cancer1. Paclitaxel, which in itself is not watersoluble, is given intravenously and most products made available today contain CrEL. Apealea is a freeze-dried powder dissolved in a conventional solution for infusion without addition of CrEL. It is Oasmia’s first product based on XR17, and the product is approved for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer in combination with carboplatin in the EU/EESA. Furthermore, the product has orphan drug designation in the US for the indication of ovarian cancer. In Russia, Apealea is distributed as Paclical by Oasmia’s partner Hetero Group and in Turkey and Israel Medison Pharma owns the distribution rights. A launch team has been formed by Oasmia as a first step in the commercialization of Apealea in the EU.
In addition to the development of Apealea for the treatment of ovarian cancer, Oasmia also intends to increase the commercial potential of the product by demonstrating its potential through several clinical studies in multiple cancer indications. Oasmia assesses that data from the planned studies will widen the approved indications of the product as well as increase clinics’ interest in the use of Apealea.
CrEL is a commonly used solvent for intravenous drugs that are insoluble in water. Compared to the most of the existing paclitaxel products Apealea does not contain the solvent CrEL. CrEL is known to enhance the risk of serious adverse events such as neurotoxicity and hypersensitivity reactions. If these side effects occur during treatment with paclitaxel products containing CrEL (paclitaxel-CrEL), this often results in interruption or termination of the paclitaxel treatment.
Due to the high risk of hypersensitivity, patients receiving paclitaxel need premedication with corticosteroids which itself has significant side effects. Corticosteroids are also immunosuppressive and in patients with cancer, an active immune system is key in fighting the disease. It is also debated how immune suppression with corticosteroids impacts the effect of so-called Immuno-Oncology Therapy (“IO”) which is acting through stimulating the body’s own immune response to fight the cancer.
Since Apealea does not contain CrEL and is nanomolecular, premedication is not mandatory. This allows for the drug to be given in shorter time than paclitaxel (one hour compared to four-five hours). Further, the dose of Apealea can be increased (250 mg per square meter of body surface) compared to paclitaxel-CrEl, which has dose limitation due to the solvent (175 mg per square meter of body surface).
Oasmia has conducted five clinical trials with Apealea to evaluate dosing, compare pharmacokinetics against paclitaxel and Abraxane (also a paclitaxel product free of CrEL) and to ensure anti-cancer efficacy. The efficacy was studied in a pivotal, randomised clinical trial of 789 women with relapsed ovarian cancer in combination with carboplatin. Key findings in the dose finding study and pharmacokinetic studies have been that Apealea can be given in significantly higher doses and in a shorter time-span (one hour compared to four-five hours) than paclitaxel-CrEL as well as that Apealea is pharmacokinetically bioequivalent to Abraxane. In the clinical phase III study, it was demonstrated that Apealea is non-inferior to paclitaxel when given in combination with carboplatin.
Doxophos is a patented formulation of the cytostatic doxorubicin in combination with XR17. Doxorubicin is one of the most widely used substances for the treatment of cancer since 1950. Oasmia has received market approval for Doxophos in Russia as a hybrid pharmaceutical (improved generic pharmaceutical) for many forms of cancer, amongst others cancer of the blood, the skeleton, the breast, the prostate and the lungs.
Oasmia is currently defining the target product profile needed for Doxophos to be competitive in the European and US market, which will then guide Oasmia in the next steps of clinical development.
Docecal is a new formulation of docetaxel, which is a semi-synthetic, next-generation taxane to paclitaxel, both of which are a type of cytostatics. Docetaxel is the active substance in Taxotere®, which is marketed by Sanofi. Docetaxel has been used extensively, including in the treatment of breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cell lung cancer. Taxotere is given intravenously and contains polysorbate 80 and ethanol. Ethanol can have negative effects on patients and the FDA has specifically issued warnings for injectable drugs containing ethanol. Similarly to Cremophor EL, polysorbate 80 is associated with severe adverse effects such as acute hypersensitivity and oedema. To minimize these side effects, patients are required to be pre-treated with corticosteroids.
Oasmia’s Docecal formulation is free of ethanol and polysorbate 80 and, similarly to Apealea, reduces the need for premedication. The composition of the excipient used in the development of Docecal differs from that used in Oasmia’s other drug candidates and in Apealea. The excipient in Docecal consists of just one component (XMeNa) instead of two (XMeNa/13XMeNa). XMeNa proved to be just as effective for the solubility of docetaxel via micelle formation as the previously developed composition with two components.
Oasmia has conducted two clinical studies with Docecal; a pharmacokinetic phase I study and a first phase II / safety study. The results showed that Docecal has a bioequivalent pharmacokinetic profile with docetaxel-p80, that Docecal is associated with fewer side effects, and that the efficacy of the treatments measured as a tumour response is comparable later than as defined in the study protocol. The study also showed that significantly fewer patients treated with Docecal were treated with corticosteroids compared to patients included in the docetaxel-p80 group. Oasmia’s goal is to develop Docecal to be used in indications where docetaxel is efficient, with a special emphasis on combinations or sub-indications that allow for a unique positioning.
Cytostatic preparations have historically been used as individual preparations. Currently, combination therapies have become standard treatment for many forms of cancer such as ovarian cancer, first-line breast cancer, prostate cancer and lung cancer. OAS-19 is a combination of XR17 and two frequently used cytostatic substances in a single micelle. OAS-19 utilizes a mechanism for double encapsulation and release of the cytostatic substances in one and the same infusion and can form a new platform for future development of product candidates. By combining two cytostatic drugs in one formulation, Oasmia anticipates that OAS-19 can give doctors the opportunity to dose cytostatic therapy in one single infusion instead of through two consecutive infusions. Thus, infusion times and treatment costs could be reduced, and hospital visits shortened.
Pre-clinical studies have shown promising results and Oasmia is evaluating the potential of different combinations being addressed for future development.