Laboratory research of cancer diseases, rack with RNA samples

In the current oncology therapeutics market, an estimated $45 billion is brought in through cytogenic therapeutics. Of that amount, 70% is attributed to generic cytostatics, which are largely dominated by paclitaxel-based products Taxol and Abraxane? (Celgene). In fact, before going generic, Taxol brought in around 1.6 billion dollars annually, and it was used for 16 cancer indexes. Just last year, Abraxane?s sales totaled $947 million, a 28% increase from the prior year. Given the popularity of these paclitaxel-based therapeutics, there is a significant market opportunity for innovation and competition. [1]

Oasmia Pharmaceutical AB, a company based in Uppsala, Sweden, has recently announced (November 5, 2015) that their previously published findings from a comparison of Paclical? vs. Abraxane? done on women with metastatic breast cancer have been confirmed. Paclical showed nearly identical concentration curves of both total and unbound paclitaxel as Abraxane. Paclical may not only become an alternative option to current US-approved paclitaxel therapeutics, but may also have several unique advantages due to their potentially safer and more cost-effective nanoparticle technology. [2]

… while targeted therapy research is prioritized in the industry, it will take a long time to get to the level where chemotherapeutics will not be used…

The basis of Oasmia?s research stems from their long term investments in nanotechnology, which they hope can bring forth novel, creative solutions to all stages of drug development. They are currently developing new semi-synthetic derivatives including retinoids and polyunsaturated fatty acids, which have already lead to promising results.

The company?s nano-therapeutic technology platform, XR-17, has allowed for Paclical to be made solvent-free and fully water-soluble. Researchers at Oasmia believe that this provides several clear advantages over their competitors, including a possibility for increased dosage, shorter infusion times, and eliminating the need for pre-medications. We had an interview with Julian Aleksov, Executive Chairman of Oasmia Pharmaceutical AB, who believes that the XR-17 platform will allow the company to become a significant contributor in an already well-established market.

XR-17 Nanoparticle Technology
Nanotechnology concerns nanoparticles that carry and release pharmaceutical agents to a desired location in the body. This technology is especially advantageous when used with drugs that have poor water solubility on their own. Oasmia uses XR-17, a vitamin A derivative, as the basis for their current non-particle and highly soluble drugs. This novel excipient is able to form micelles combining water soluble and water-insoluble substances in order to minimize the need for toxic solvent additions. These micelles, which are able to achieve sizes between 20-60 nanometers long, are dual ended molecules, with one side being fat-soluble and the other being water- soluble. They are able to surround a pharmaceutical agent and form spheres around a drug, serving to protect and increase the drug?s potency until its full metabolism.

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In fact, when bound to paclitaxel, the XR-17 molecule has been shown to achieve a carrier vs. API ratio of (1.3:1.0), significantly lower than that of Abraxane (9:1.0) and Taxol (88:1.0). ?With XR-17, we can transform a very high amount of unbound drug to a water soluble formulation?, stated Aleksov, ?and with that we have a much higher inventive step and advantage.? [3]

When compared to Taxol in an open, cross over, multi-center pharmokinetics study, plasma concentrations of total paclitaxel were higher in patients that received Taxol as compared to Paclical, but the unbound plasma concentrations were similar across the two drugs. And now recently confirmed, in a study comparing Paclical to Abraxane, 28 metastatic breast cancer patients that were randomized and received a sequence treatment of Paclical +Abraxane or Abraxane + Paclical, showed nearly identical concentration of total and unbound paclitaxel following a one hour infusion. According to Aleksov, while both drugs are showing equal concentration curves, there is key difference in their chemical composition. ?Abraxane is artificially compiled.?? Noted Aleskov, ?we are the only system on the market to which once water is added, the system can (be) create(d) naturally.? [4]. Importantly, the use of water-soluble nanoparticles can allow for substances that are normally difficult to manage, to be formulated in a way that may be compatible with a wide variety of medical equipment and solutions.

Advantages of Low Carrier vs. API Ratio
One advantage of the XR-17 carrier is that there is a reduced hypersensitivity in comparison to the current therapeutics. In fact, in the phase III comparative study of Taxol and Paclical , the number of patients with hypersensitivity reactions was the same for Paclical with no pre-medication as with Taxol with pre-medication with corticosteroids and anti-histamines. In the comparative study with Abraxane, there were eleven grade 3 adverse events for Paclical, and ten for Abraxane, with the most common being neutropenia in both cases.

While both studies have shown non-inferiority to Abraxane and Taxol, researchers at Oasmia are confident that their technology will lower production costs and enhance patient convenience by eliminating pre-medication use and shortening infusion times, as well as by making higher doses possible. [4]

Expanded Applications and Combination Therapy
Importantly, the XR-17 platform has potential for more expanded applications than those currently being used. According to Aleksov, the technology can be applied across multiple APIs, ?we can handle 70% of the products that have solubility problems- that is out potential with this technology.? And while the drug has an index for monotherapy, it can have large impact in the need for chemotherapeutics being used in combination therapies.

Recently, targeted cancer therapies such as anti-body drug conjugates or ADCs are becoming more popular for their unique tumor-targeting properties. Targeted therapies are showing exciting potential to become more effective than traditional chemotherapeutics while significantly minimizing adverse effects. According to Aleskov, while targeted therapy research is prioritized in the industry, ?it will take a long time to get to the level where chemotherapeutics will not be used.? For now, targeted therapies are being applied in combination with existing chemotherapeutics. ?The use of combination therapy is growing?? stated Aleksov, ?In 5-10 years, there will be a need for chemotherapeutics that are better than those currently available.?

The XR-17 nanotechnology platform currently has a patent protection filed to 2028. Paclical received market authorization in the Russian Ferderation in April 2015, and will be approved via the 505 (b) (2) regulatory pathway in the US as a reformulation of paclitaxel. ?Paclitaxel has been used by physicians for over 20 years?, noted Aleksov ?and our mission is to enter the already existing market. A significant market means room for more key players.? [5]

Last editorial review: January 18, 2016.

Featured image: Laboratory research of cancer diseases. Courtesy: ? 2016 Fotolia.? Used with Permission.

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