One of the most important stages in the development of a drug is the evaluation of how it should be administered. Adequate administration has a direct effect on the drug's efficacy, as it influences factors such as its pharmacokinetics, pharmacodynamics, safety, immunogenicity, bio-recognition of the drug, among others. On the other hand, investigation in this field allows minimization of such factors as degradation of the active substance, prevention of side effects or increases in the bio-availability of the drug in the body.

ROVI has developed a leading-edge research line in the field of drug delivery or depot systems. This is generally a subcutaneous or intramuscular injection of a pharmacologically active agent that releases the active substance in a constant flow over a long time period. The technology developed by ROVI, ISM® technology, is based in the formation of in situ implants for extended release of drugs.

Extended release systems ISM®

In situ forming systems (ISM®) have emerged as a very attractive possibility for the extended release of bioactive macromolecules.

Over the last few years, the fast development of the ISM® technology has made possible that the depot formulations to become in science fact. ISM® technology is based on a solid and stable polymeric matrix system that contains a drug. The product is reconstituted to an injectable fluid that precipitates in situ (inside the body) after the injection, resulting in the formation of solid or semisolid implants, by solvent diffusion to body fluids.

ISM® technology overcomes most of the current difficulties related with the oral and parenteral extended release formulation combining the advantages of existing technologies such as preformed microparticles and implants. Our technology allows the extended delivery of compounds administered by parenteral route with the following key advantages: less variability, enhanced stability, rapid reconstitution and easier injection, making easier for the patient to follow the prescribed treatment.

ISM® systems have the following advantages over other marketed technologies: (I) ease administration as it is less painful, (II) zero-order kinetics, (III) reduction of the burst effect in drug release and greater reproducibility in the release profiles, (IV) highly effective encapsulation, (V) high performing process and, finally, (VI) active substance´s stability improvement.

This field of research comes up from the ROVI´s interest in the development of formulations based on ISM® technology. This technology would allow periodic administration of drugs which are administered daily in chronic and prolonged treatments, in order to improve the treatment compliance and the patient quality of life. This novel approach allows ROVI to be introduced and compete in new therapeutic areas. Extended release formulations based on ISM® technology are currently being developed for psychiatric and oncologic drugs due to their industrial potential, commercial and health interest.

In September 2010, the experimental stage for the first Phase I trial of Risperidone- ISM® began on healthy volunteers. The aim of this trial was to evaluate the pharmacokinetics and tolerability of a single intramuscular administration of Risperidone ISM®, the first candidate for the new delivery system. This trial has served, not only to confirm the pharmacokinetic profile of this depot formulation for the monthly administration of risperidone, but it has served as proof of concept for validating ISM® technology for future developments. In this regard, a new quarterly formulation of letrozole is in advanced preclinical development. This drug is a well-established aromatase inhibitor for the treatment of dependent-hormone breast cancer.

During 2012 ROVI built in Madrid a manufacturing plant of investigational Medicine Products with the ISM® release system technology, equipped with innovative and unique machinery for the filling of solid compounds in syringes under the guidelines of good manufacturing practices. Also, is building a factory which will let to produce the new drugs with ISM technology that contain high strength active principles, as letrozole, which is planned to start clinical development phase soon. The first human clinical trial of letrozol ISM® is expected for 2016, and the medication used there will be manufactured at this factory.