The Risks and Rewards of Rare Diseases

Definitions of rare diseases can vary. In the US, a disease is considered rare if it affects fewer than 200,000 Americans. Europe considers a disease rare if it affects fewer than 1 in 2000 people. Collectively, however, rare diseases make up a significant healthcare burden. More than 7000 rare diseases have already been identified and more will certainly follow. The UK has estimated that a rare disease will affect around 1 in 17 people during their lifetime.

According to Kevin Wake, President, Uriel Owens Sickle Cell Disease Association of the Midwest, “Rare disease research is not only a moral responsibility, but should be a strategic opportunity that can drive scientific progress and innovation, as well as improve public trust in the pharma industry.”

The need is significant, and the topic is emotive. Many rare diseases affect children – who do not survive to become adults because there is a lack of treatments. Research is improving, as well as regulatory pathways that encourage and reward the development of orphan medicines. Orphan drug designations and approvals have increased, but cost and accessibility remain key hurdles, as does return on investment for developers. According to Wake, some of the most exciting breakthroughs in rare diseases are coming in the form of advanced medicines, such as gene therapy and CRISPR-based treatments. However, these therapies are very expensive to develop and manufacture.

Bluebird bio and the ROI challenge
 

The fall of bluebird bio is one example of the challenges of commercializing expensive therapies for rare diseases. The company has three FDA-approved gene therapies: Lfygenia (lovotibeglogene autotemcel) for sickle cell disease, Skysona (elivaldogene autotemcel) for cerebral adrenoleukodystrophy, and Zynteglo (betibeglogene autotemcel) for beta-thalassemia.

Bluebird bio was once considered a key innovator in gene therapy, with its stock being valued at over $2000 per share in 2018. However, it has struggled to sell its therapies. In 2021, the company ceased commercial operations in Europe because it could not agree a payment deal with authorities. Recently, bluebird bio recently announced that it would be acquired by the investment firms Carlye Group and Sk Capital Partners for just $3.00 per share. Shareholders may be entitled to an additional $6.84 per share in contingent value rights, if the value of the company’s product portfolio reaches $600 million in net sales by December 31, 2027, which many believe is unlikely. 

The sale to the Carlye Group and Sk Capital Partners was seen as the only way to save the company. A statement from bluebird bio explained, “Following a comprehensive review of bluebird’s strategic alternatives, including meeting with more than 70 potential investors and partners over a period of five months, and a third and final denial by the Federal Drug Administration of bluebird’s appeal for a priority review voucher, the bluebird Board determined that, absent a significant infusion of capital, bluebird is at risk of defaulting on its loan covenants. The bluebird Board has decided that this transaction is the only viable solution to generate value for stockholders.” 

Bluebird bio is not the only company struggling with gene therapies for niche indications. Even big pharma has its troubles, evidenced by Pfizer’s decision to discontinue its hemophilia gene therapy Beqvez – reportedly because of low demand.

Balancing costs
 

Developing drugs for small patient populations comes with huge risks, and it would be a travesty if patients missed out because companies aren’t rewarded for their innovation. That said, what can be done when drugs are just too expensive? Bluebird bio’s Skysona therapy was priced at nearly $3 million per treatment. At the same time, because cell and gene therapies are also in their early days, they can come with safety and efficacy concerns, which brings price tags under even greater scrutiny. Skysona, for example, has been associated with life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia.

Despite the side effects, however, cell and gene therapies can be life changing. An article in Nature Medicine recently reported on the long-term outcomes of CAR T cell therapy. In 2005, a four-year old patient with neuroblastoma received a CAR T-cell therapy developed at the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital. Today, that patient remains cancer free. She has never required any other treatment – and has gone on to have two healthy children. You can’t put a price on that.