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March 19, 2020

Innovative nanopharmaceuticals will allow targeted approaches to treating cancer

By GlobalData Healthcare

Nanopharmaceuticals have many physical and biological advantages compared to conventional medicines, such as enhanced efficacy and reduced toxicity, which are particularly important in treating cancer patients. One of the main areas of opportunity for nanomedicine to date has been oncology, with high levels of R&D activity detected in the field. For example, of the more than 230 nanopharmaceuticals in clinical development identified by GlobalData, 75% are in development for oncology indications, including many hard-to-treat cancers with few treatment options.

A relatively new class of nanopharmaceuticals are immunoconjugates, and these signify an important development in the armamentarium of cancer therapies. Immunoconjugates are actively targeting medicines that deliver a toxic payload to tumour cells via a monoclonal antibody (mAb) that binds to a specific target antigen expressed on cancer cells. Upon binding to the tumour cell surface, the immunoconjugate is internalised and releases its payload intracellularly, leading to cell death. This strategy has enormous potential in oncology as it reduces the associated toxicities and side effects of highly potent chemotherapy and radiotherapy. Immunoconjugates can be classified according to the payload used. For example, antibody-drug conjugates (ADCs) deliver a cytotoxic chemotherapy payload, antibody-antibiotic conjugates (AAC) deliver potent antibiotics, and antibody-radionuclide conjugates (ARCs) deliver radionuclides. There are currently nine immunoconjugates approved in the US and Europe, and over 100 in clinical development, highlighting the significant potential of this class of nanomedicines. According to GlobalData’s Drug Sales and Consensus Database, the nanopharmaceuticals with the highest forecast sales in 2025 are all ADCs, and include Daiichi Sankyo / AstraZeneca’s Enhertu ($3.6B), Seattle Genetics / Takeda’s Adcetris ($2.1B), and Roche’s Kadcyla ($1.9B).

Other types of novel nanopharmaceuticals that allow targeted cancer treatment include smart nanocarriers that release drugs at tumours once triggered by internal or external stimuli, such as changes in pH, electric or magnetic fields, heat, and ultrasound. These are important for drug delivery purposes, as they allow the controlled release of the loaded drug, which reduces local side effects and increases efficacy. MagForce AG’s Nanotherm is approved in Europe and utilises aminosilane-coated superparamagnetic iron oxide nanoparticles (SPIONs) for the local treatment of glioblastoma. After Nanotherm is injected directly into the tumour, an alternating magnetic field is applied to heat the SPIONs, causing the temperature of the tumour microenvironment to increase to 40°C–45°C, causing cell death. This is known as magnetic hyperthermia. Nanospectra’s AuroLase is in development for the treatment of various cancers and utilises the unique optical tunability of a new class of nanoparticles, called AuroShells. The AuroShells are delivered intravenously and accumulate in the tumour, which is then illuminated with a near-infrared laser. The nanoparticles absorb the laser energy, convert the light into heat, and thermally destroy solid tumours without damaging adjacent healthy tissue.

Radiotherapy is one of the most common treatments for cancer, with approximately 50% of patients currently receiving this as local tumour treatment. However, its efficacy is limited by the toxicity of exposure to surrounding normal tissue, with many patients receiving a dose that is insufficient for tumour destruction to avoid unfavourable side effects. Nano-radioenhancers are nanoparticles with high atomic numbers that have strong interactions with X-rays, thus improving the efficacy of local radiation therapy. In April 2019, Nanobiotix’s Hensify received European approval for a first-in-class radioenhancer for the treatment of locally advanced soft tissue sarcoma (STS). Hensify is an aqueous suspension of inorganic crystalline hafnium oxide nanoparticles that is injected into a tumour prior to radiation therapy. When Hensify is exposed to ionising radiation, the particles amplify the killing effect of the radiation in situ, destroying tumours. In comparison to conventional radiation therapy, Hensify technology improves the energy dose within tumours without damaging healthy tissue.

Another application of nanomaterials in personalised treatment in oncology is theranostics, a novel concept that involves the integration of diagnosis and treatment in a single platform for cancer patients. Theranostic nanoparticles can be developed in a number of ways. Firstly, they can be engineered by conjugating therapeutic agents, such as chemotherapy or photosensitisers, to existing imaging nanoparticles, such as quantum dots, gold nanocages, and iron oxide. They can also be created to encapsulate both imaging and therapeutic agents in biocompatible nanosystems. Lastly, certain inorganic nanoparticles have both imaging and therapeutic inherent characteristics, such as gold nanoshells and SPIONs. Theranostics is an area of research that has gained increased interest over the past decade. The field is still young, with no theranostic nanoparticles currently approved for use, and most still in the preliminary stages of clinical development. NHTherAguix’s theranostic candidate AGuIX is in Phase II development for brain cancer. The nanoparticle is composed of inorganic polysiloxane and gadolinium, which is a commercially available magnetic resonance imaging (MRI) contrast agent. Gadolinium has a high atomic number, leading to strong interactions with X-rays, allowing AGuIX to act as a radioenhancer while simultaneously allowing an increase of tumour contrast after injection.

Non-targeted cancer treatments can cause significant side effects due to their impact on healthy tissue. The development of targeted therapies with reduced side effects is key to improving patient outcomes and treatment efficacy. GlobalData believes that nanomedicine is expected to play a key role in this field in the future, especially as cancer rates are expected to increase significantly over the next ten years.

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