How Allogeneic Stem Cell Therapies Can Transform Prospects In Inherited Retinal Diseases

Advanced therapies have revolutionized the field of medicine, offering the potential to go beyond just alleviating symptoms. In recent years, we have seen a tremendous increase in the number of cell and gene therapies in development. While these treatments have potential in a wide range of therapeutic areas, Santen sees a particular promise in allogeneic stem cell therapies, particularly the use of human retinal progenitor cells (hRPCs), to treat inherited retinal diseases.

Defining Times: The Rise of Advanced Therapies

We are living through a defining period for the future of advanced therapies. While the transformative potential of these treatments is widely acknowledged by the scientific community, patients, healthcare professionals, and beyond, the sector faces a number of challenges across key dimensions of the product life cycle. Ongoing discussions at the policy level, such as the implementation of the new pharmaceutical strategy by the European Commission and the revision of current legislation on rare diseases, will determine future accessibility and affordability of advanced therapies. At this pivotal time, I take the opportunity to explore the many benefits cell therapies bring to ophthalmology and to highlight why Santen is investing in this exciting and promising field.

Within the domain of cell therapy, two distinctive methods for cell collection have emerged, autologous (self-derived) and allogeneic (donor-derived). Each has benefits in specific clinical applications. For the treatment of inherited retinal disorders, allogeneic methods using hRPCs offer a number of advantages.

Allogeneic Stem Cell Therapies in Inherited Retinal Diseases

The differences in the effects between multipotent and more specialized cells such as hRPCs are complex, and a number of cell types are being studied in ophthalmic diseases. hRPCs are a “descendant” of stem cells derived from fetal retinas. They release neurotrophic factors that restore cellular function, including that of diseased photoreceptors and neurons, and have the ability to differentiate under certain conditions. This means they have a huge potential in a number of degenerative retinal diseases, including retinitis pigmentosa, a rare inherited eye condition caused by various genetic defects, and one of the leading causes of inherited blindness.

The main risk associated with allogeneic therapies is immune rejection. In some indications (where there is exposure to the systemic immune system),an immunosuppressant may be administered in order to reduce immune response. For such conditions, the use of autologous therapies means that the invasive procedures required to obtain cells from the patient undergoing the treatment is justified.

However, the eye is one of the few sites in the body that possesses a degree of immune privilege. While this privilege is not absolute and depends on a number of factors, including an intact retinal pigment epithelium monolayer, 

the risk of ocular immune response has been shown to below, giving allogeneic stem cell therapies the potential to be safe to use in a wide variety of ophthalmic indications.

Compared to their autologous counterparts, allogeneic therapies generate a number of benefits owing to their “off-the-shelf” characteristic. They rely on limited, sometimes single sources of cells that can be replicated many times, frozen, and subsequently used to treat large numbers of patients. This gives rise to considerable potential economies of scale in addition to the greatly reduced treatment burden upon the patient.

"Compared to their autologous counterparts, allogeneic therapies generate a number of benefits owing to their “off-the-shelf” characteristic"

In addition, the administration procedure in allogeneic therapies has the potential to be minimally invasive, such as with intravitreal delivery when administering hRPCs to treat retinal disorders where neurotrophic factors are relied upon as the mechanism of action.

Santen, Advanced Therapies and Achieving Happiness Through Vision

Santen is a global specialist in ophthalmology, committed to reducing the loss of social and economic opportunities for people around the world due to eye conditions. We have a commercial presence in over 60 countries and a portfolio that includes both over-the-counter and prescription medicines as well as medical devices. In 2020, we made the first of what we hope will be many investments in the advanced therapy field, through the conclusion of our licensing agreement for an investigational hRPC therapy in late-stage clinical development. If approved, it has the potential to positively impact the condition of patients with retinitis pigmentosa and potentially other retinal degenerative diseases. 

To support our entry into the field, we are building a business model that combines the agility of a start-up with Santen’s expertise and heritage in order to develop innovations at a pace that can benefit society and transform lives. While our hRPC therapy remains our primary focus, we are also building a longer-term strategy focused on developing a pipeline of advanced therapies. Our new expert team will maintain an entrepreneurial and agile mindset so that we can accelerate our hRPC therapy program and build a successful and sustainable platform in this field.

We see this addition to our pipeline as a significant step in achieving our world vision of creating happiness around the world through vision. Entering the advanced medicines space will allow us to develop and commercialize therapies that can address important unmet medical needs in ophthalmology, ultimately moving us towards our goal of creating a brighter future and better life for patients impacted by rare and sight-threatening diseases.