Medication development in general
Developing a new medication is initiated by research, followed by a preclinical phase in which various types of tests and experiments are performed in the lab. These can include in vitro experiments – i.e. test tube studies, or studies that are not performed on animals or humans. In some instances, they can also be conducted ex vivo, on living tissue taken from the body. This work leads to clinical tests on humans, in vivo, when the conditions exist to achieve a safe, successful result. Clinical studies are performed in several phases, each subject to specific requirements.
The development of a medication is a process that requires substantial data, clinical studies and the approval of various medication authorities. Clinical studies can be broken down into a number of different phases:
- Clinical phase I studies are those on involving healthy subjects or in some cases, ill patients, depending on the substance/therapy area. Toxicity and tolerance are studied.
- Clinical phase II studies are divided into phase IIa and phase IIb studies, and are preliminary studies on patients to study treatment efficacy.
- Clinical phase III are more extensive studies on a large number of patients and provide the documentation needed to be able to register a new medication.
The basic principles for developing a new medication are based on safety and efficacy, and the clinical studies are designed for this purpose. However, it is possible to develop a substance for clinical studies without detailed knowledge of how the intrinsic molecular mechanisms give a certain pharmacological effect. The board of DexTech believe that it is important from a scientific and value-creation perspective to understand the biological mechanism or signal value the company’s products influence. In-depth knowledge of the mechanism of action can also be a big help to explain and understand observations in clinical studies.
Before commercialisation of a medication can be done, the candidate medications have to undergo preclinical and clinical studies to demonstrate safety and efficacy, and to obtain the necessary approvals from the authorities. How long a study might last cannot be determined exactly beforehand, and the outcomes of preclinical and clinical studies can vary. Commercialisation can also require other manufacturing processes.
DexTech has developed three candidate medications using GuaDex, its own technology platform developed in-house. OsteoDex is the company’s main candidate. A successful preclinical phase I/IIa study has been performed for OsteoDex, and an international phase IIb study is ongoing.
Other candidate medications are SomaDex for treating certain pituitary gland tumours, neuroendocrine tumours and palliation of castration resistant prostate cancer, CRPC, and CatDex, a potential antimicrobial agent.
Ongoing phase IIb study
The phase IIb study investigates how effective OsteoDex is for treatment of CRPC. An international multicentre study ongoing in i Sweden (Norrlands University Hospital in Umeå, Södersjukhuset in Stockholm and University Hospital of Örebro), Finland (Tampere University Hospital), Estonia (East Tallin Central Hospital och Tartu University Hospital) and in Latvia (Riga East University Hospital and Daugavpils Regional Hospital).
Emphasis is placed on study design to ensure an unambiguous result with regards to therapeutic effect. In this context, it is relevant that Sten Nilsson (founder and board member) along with colleagues designed and conducted the Algeta/Bayer “First-in-man-study” and subsequently randomised phase IIb study for Alpharadin (Radium-223), now marketed under the name of Xofigo. Nilsson took part in the design and conducting of Alpharadin’s (Xofigo’s) phase III study (ALSYMPCA). Xofigo achieved market authorisation from the FDA in May 2013 and from the EMA in December 2013. Nilsson thus has valuable experience within successful study design and conducting clinical studies for new preparations within this field.
The ongoing phase IIb study includes 60 well-defined CRPC patients. The patients are divided between three active therapy arms (blinded distribution). Treatment is given every second week for max. 20 weeks. The study is estimated to be full recruited during 2017. All patients taking part in the study will be given access to the best available standard treatment (Best-Standard-of-Care). Upon signs of disease progression, the patient will be offered continued best standard-of-care (BSC), suitable for the situation in question.