GSK advancing orphan drug discovery

GlaxoSmithKline (GSK) has announced a strategic alliance with Italy's Fondazione Telethon and Fondazione San Raffaele. The alliance aims to research and develop novel treatments to address rare genetic disorders, using gene therapy carried out on stem cells taken from the patient's bone marrow (ex vivo). The announcement comes as GSK outlines the strategy and focus for its unit dedicated to rare diseases, which was established in February 2010. 

Less than 10 per cent of patients with the 6,000 – 8,000 recognised rare diseases are currently being treated worldwide. Of the untreated conditions, GSK plans to target those diseases where they realistically believe they can make a significant contribution. The company has adopted a strategic approach to narrow down the list of disease targets to around 200, which will be flexible as knowledge and understanding changes. 

"Not all rare diseases are 'reversible' or can be significantly improved by therapeutic interventions and it will be vital that we are science-led in making these distinctions," said Marc Dunoyer, global head of GSK Rare Diseases. 

Additionally, the company will utilise its R&D capabilities from across the entire GSK organisation to generate a large candidate pool. 

"We do not want to become a specialist in a single area of rare diseases, such as oncology, as we believe this will limit the potential of the unit. We want to create a diverse portfolio of compounds looking at a broad spectrum of rare diseases," said Dunoyer.

Critical to this will be augmenting the company's in-house capabilities through collaborations with external organisations and institutions. This process has already begun: in April GSK entered into a potential $1.5bn deal with Isis Pharmaceuticals to develop new drugs for rare and serious diseases, using Isis' antisense drug discovery platform. 

GSK also has existing collaborations with Prosensa and JCR Pharmaceuticals, in addition to the newly announced alliance with Fondazione Telethon and Fondazione San Raffaele, which capitalises on research performed at the San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), a joint venture between Fondazione Telethon and Fondazione San Raffaele established since 1995.

Under the terms of the new agreement, GSK will gain an exclusive licence to develop and commercialise an investigational gene therapy, for ADA Severe Combined Immune Deficiency (ADA-SCID) - a rare and life-threatening immune deficiency, which affects approximately 350 children worldwide.

Phase I/II studies have already demonstrated the potential of this treatment option to restore long-term immune function and protect against severe infections in children with ADA deficiency.  

In addition, GSK will co-develop with Fondazione Telethon and Fondazione San Raffaele, six further applications of ex vivo stem cell therapy, using a new gene transfer technology developed by HSR-TIGET scientists, with the potential to treat a range of rare disorders, including metachromatic leukodystrophy (MLD), Wiskott-Aldrich Syndrome (WAS), beta-thalassemia, mucopolysaccharoidosis type I (MPS), globoid leukodystrophy (GLD) and chronic granulomatous disorder (CGD). Clinical trials for WAS and MLD were initiated at HSR-TIGET last spring and are currently recruiting patients. 

All of these disorders have a molecular mechanism that is well understood and are caused by faults in a single gene, making it possible for this ex vivo gene technology to correct the patient's own bone marrow stem cells. When the treated stem cells are returned to the patient they express the corrected protein, providing an opportunity to treat the disease and side-step much of the risk associated with immune-incompatibility that comes from stem cells supplied by a donor.

"This alliance is an important addition to GSK's growing portfolio in rare diseases and advances the work our stem cell researchers have been doing to deliver transformative regenerative therapies," said Dr Philippe Monteyne, head of development and chief medical officer for GSK Rare Diseases.