Life changing treatments for rare disease – a beacon of hope

rare diseases

By Sander Slootweg, managing partner, Forbion

More than 300 million people around the globe are affected by a rare disease. This number does not even take into account the impact on these individuals’ support units that includes family, friends and caregivers.

A rare disease is defined as a disease that affects no more than 1 person in 2,000. While the existence of rare diseases has been known for many centuries, currently around 8,000 have been identified affecting an estimated 30 million people in the EU alone. Rare diseases are present across the medical spectrum and include cancers, neurological and neuromuscular diseases, metabolic diseases and a multitude of skin, bone, kidney, blood and skeletal disorders. Many have genetic origins, and some are ultra-rare conditions, affecting less than 1 in 50,000 in the EU. 

The Orphan Drug Act changed the game

Developing medicines for rare or ultra-rare patient populations has historically been a challenge because it made little or no commercial sense to big pharma who were often the developers. This all changed with the passing of The Orphan Drug Act of 1983 in the United States, which revolutionized the industry overnight.

This legislation was brought in following recent medical advances to deliberately incentivize the pharmaceutical industry to invest in the development of new therapeutics to meet this high unmet medical need. In 2000, the EU followed suit with the adoption of the Orphan Regulation together with the establishment of the Committee for Orphan Medicinal Products (COMP) which is responsible for recommending orphan designation of medicines for rare diseases in the EU.

Despite recent medical advances, for the vast majority of the more than 8,000 monogenetic diseases, affecting about 1% of the world population, there is still no approved or effective treatments. It is also important to remember that a single therapeutic for a specific orphan disease is often inadequate, due to the unique expression of most rare diseases from patient to patient.

Funding programs for rare disease treatments

Recently, certain Big Pharma have deprioritized their rare disease research portfolios due to regulatory changes and perceived reimbursement challenges. However, what are potential hurdles for Big Pharma may be attractive opportunities for healthcare specific venture capital and private equity funds. These small to mid-sized entities are equipped with the resources, network, experience, and knowledge to rival Big Pharma, to address these deprioritized programs, form new companies, and support the development of promising, innovative and novel treatments.

Forbion was an early investor in rare disease programs. Our investors believe that investing in orphan drugs can address some of the most serious and rare diseases with the highest unmet need.

Forbion has a successful track record spinning de-prioritized assets out of pharma companies like Amgen and MTPC, leading to successful companies like New Amsterdam Pharma. 

However, building fully integrated orphan drug companies requires a substantial amount of capital as these therapies may need funding all the way from discovery and development through to commercialization.

Another example of an active portfolio company in the orphan space is Azafaros, which develops small molecule drugs for patients with lysosomal storage diseases and was seeded by our early-stage joint venture partner BGV, with Forbion Ventures joining at the Series A stage in 2020.

Precision therapies for treatment of rare diseases

One of the leading innovations that has helped form the basis of advanced therapies for treatment of rare diseases has been precision medicine technologies, such as gene therapies. Precision medicine specifically targets the cause of disease pathology, improving the safety and efficacy of therapy by circumventing interference with healthy tissue, making it an ideal therapy type to treat rare diseases as, more often than not, the disease manifests itself by shielding behind unaffected healthy tissues or organs.

It has been more than three decades since the initiation of the first gene therapy clinical trials in 1990, and the industry and research in this field has grown exponentially. However, several questions still need to be asked: Where are we now? What have we learned? And, how much more is there to do? The simple answer is, ‘a whole lot more!’

The development of a successful gene therapy is extremely complex and, in the case of many companies developing these therapies, requires a complete development of the manufacturing process from scratch, as well as overcoming many other hurdles. 

Precision medicine specifically targets the cause of disease pathology, improving the safety and efficacy of therapy by circumventing interference with healthy tissue. Just two years ago Forbion created a new precision medicine company, VectorY Therapeutics. VectorY treats treat rare diseases of the central nervous system. Forbion established VectorY by combining the expertise, experience and vision of Forbion operating partners and industry leaders, Sander van Deventer and Carlo Incerti.

Van Deventer has developed two gene therapies to market approval, and Incerti was a member of the senior management team and led the clinical development of many pioneering rare disease company Sanofi/Genzyme. 

Gene therapy breakthroughs

Although many challenges still exist in rare diseases therapy development which require entrepreneurs, scientists, and their teams to overcome, slowly but surely, we are seeing success stories emerge.

Two of Forbion’s former portfolio companies UniQure, and bluebirdbio exemplify this path to success. Our journey with these companies has been long: UniQure’s history tracks back to the previous century, evolving from Amsterdam Molecular Therapies (AMT) that was founded in 1998.

In 2022, AMT-061, now branded HEMGENIX, was the first FDA approved gene therapy for hemophilia B, having been licensed to CSL for commercialization in 2020. At the end of February 2022, HEMGENIX received conditional approval in Europe. This is widely considered to be a remarkable breakthrough for the indication. A single 30-minute HEMGENIX infusion leads to a long-term correction of the coagulation defect underlying the condition – and basically normalizes patients’ lives. This is compared to even the best current replacement therapies where patients still suffer from recurrent bleeds, leading to severe disabilities and an inability to lead a normal life.

Bluebirdbio’s story begins 18 years ago when the company was still known as Genetix Therapeutics.

In 2004, Forbion invested in the Series A to restart the company, recognizing its cutting-edge platform for ex-vivo gene therapy for the future treatment of beta-thalassemia and sickle cell disease. The company was rebranded bluebirdbio and IPOed on NASDAQ in 2013. Following earlier European registrations, 2022 was a significant year for bluebirdbio with two product registrations by the FDA: ZynTEGlo for beta-thalassemia and SkySona for cerebral-adrenoleukodystrophy.

Investing in breakthrough treatments for rare diseases requires the ability to recognize innovative science, and the skills and resources to navigate regulatory and financial hurdles in order to realize the ultimate goal of impacting the lives of patients.

As we observe and try to increase awareness of Rare Disease Day on February 28 Hemgenix, ZynTEGlo and SkySona are set to do just that!

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