Gene Therapy: The Future is Here

After decades of R&D, numerous lessons learned, and limited initial adoption, gene therapy has finally become a clinically and financially viable option for certain indications globally. In the early 2000’s, gene therapy was positioned at U.S. universities as promising, but largely experimental. In 2012, UniQure of the Netherlands gained EU approval for Glybera (world’s first approved gene therapy), for the treatment of lipoprotein lipase deficiency. A few years following the approval of Glybera, our consultancy started to receive more inquiries to conduct competitive landscape assessments for gene therapy companies. The early therapeutic areas and indications were mostly in rare diseases and oncology, and these remain the focus areas today. Hemophilia B, ophthalmology, cystic fibrosis, and severe combined immune deficiency in children are some of the TA’s and indications which also demonstrated early progress in the gene therapy space.

Figure 1: A patient’s T cells (purple) are genetically modified to hunt down and kill cancer cells (red) – (Source: NBC News/Steve Gschmeissner/ Science Photo Library/Getty Images)

From recent conference research, we found that most clinicians in the EU had accepted gene therapy and were interested in participating in trials. However, the first generation of gene therapies in the EU were met with limited success, and the first four of ten approved therapies were eventually withdrawn, mostly due to hurdles with reimbursement. On face value, the attractiveness is clear; for example, picture this scenario for GSK’s Strimvelis. You’re a child with a rare, inherited disease, which requires injections at least once-a-month. You find the option to go to a treatment center in Milan, Italy with your family for an “all-inclusive” therapy regimen. It is costly, but after six weeks, if all goes as planned, you go home cured and do not have to take shots for the rest of your life. The word cure doesn’t get used much these days when it comes to rare diseases and oncology, so when it does pop up, those who are connected take notice.

Cost continues to be an issue. Early drugs like Glybera cost one million euros, and were the world’s most expensive drugs. In August 2017, the FDA, in what it called a “historic action,” approved Kymriah, the first approval of a cell-based gene therapy in the United States. It was originally approved to treat children and young adults up to age 25 suffering from a form of acute lymphoblastic leukemia (ALL) who do not respond to standard treatment or have suffered relapses. Novartis set the one-time treatment price tag at $475,000 for patients who respond. Non-responders would not be charged. A couple of months later, Gilead’s Yescarta was approved by the U.S. FDA to treat adults with large B-cell lymphoma, a type of non-Hodgkin lymphoma, who have failed to respond to other treatments. The price was set at $373,000, well below Novartis’ chimeric antigen receptor T-cell therapy. CAR-T’s reprogram the body’s own immune cells to recognize and attack malignant cells. The cost debate continued in late 2017 and in January 2018, Spark Therapeutics set the price of Luxturna at $850,000 after receiving approval. Patient advocates argue that gene therapy prices will put stress on the U.S. healthcare system, with extreme predictions of bankrupting the system. Despite the criticism, pioneer manufacturers in pharma justify the cost by reminding customers of the cost and time spent to develop the drugs, and by stressing the one-time nature of treatment.

Figure 2: A lymphoma patient’s brain tumor disappeared after she received JCAR017 (Source: Lymphoma News Today)

Other major biopharmaceutical players have taken notice. The most recent example is Celgene’s acquisition of Juno in January 2018. The move was mainly made to gain access to JCAR017, a potentially best-in-class CD19-directed CAR-T which is expected to gain regulatory approval in 2019, with global peak sales of about $3 billion. Other companies, such as bluebird bio, Voyager Therapeutics, and Audentes Therapeutics, represent a growing sector of roughly 60 private and public companies working on therapies for upwards of 60 diseases, addressing market opportunities worth more than $100 billion (according to Barron’s). While the momentum is clear, the regulatory, managed care, and patient advocacy elements will continue to present challenges for new entrants. The gene therapy space is hyper-competitive, and requires consistent monitoring and assessments of companies looking to shift the paradigm in medicine.

Below is an example of gene therapy, editing, and CAR-T companies in this competitive landscape:For more information about how to maintain a competitive advantage in gene therapy, please contact Cinda Steele via [email protected] or 610-496-0080. Landscape assessments, competitor deep dives, and scenario planning are all proven as effective tools to prepare for the gene therapy era, which has begun.

– Author: Michael Kavouksorian, Team Leader, Life Sciences