Genome Medicine: The new paradigm that significantly expands the medicine market

As we enter 2019, a new age of medicine is taking off. The pharmaceutical industry started with small chemical entities, then developed complex proteins that interacted with different kinds of cells and has now reached the age of cellular and genomic medicine. With several genomic therapies approved and many companies working on genome therapies, medicine has gained new tools to address previously untreatable diseases and undruggable targets. This development significantly grows the addressable market for medicine.

Before the recent approvals gene therapies Kymriah® (Novartis), Yescarta® (Gilead/Kite) and Luxturna® (Spark) in the US, Europe was surprisingly open for these innovative medicines. In fact, Europa greenlighted market access for Glybera® (uniQure’s) all way back in October 2012. Then, in May 2016 the EMA granted marketing authorization to Strimvelis® (GSK). In total, we now have five approved gene therapies and a full pipeline of potential drugs ahead of us.

After years of basic research and clinical development, the recent breakthroughs in sequencing and genome editing have opened the gates for these therapeutic innovations.

After all, the idea of gene therapy is not new. It appeared in the 1970s, with the goal to introduce genetic material into cells in order to either allow the cell to produce beneficial proteins or repair “broken” genes.

The first scientific research was devoted to the use of healthy genetic material to replace defective genes in patients with genetic disorders. The earliest clinical studies have been held by the NIH. They were focused on delivering a synthetic functional copy of a gene into cells.

A major challenge for gene therapies was (and remains) to find a way to introduce this genetic information into the cell. Just inserting a genomic material into a cell has usually no effect. It needs to be incorporated into the nucleus of the cell instead. This is usually done by a modified virus, referred to as “vector”, that acts as a carrier for the genetic material.

This vector can be injected or given intravenously into a specific tissue in the body, where it is taken up by individual cells. This approach is called in-vivo gene therapy.

The first approved therapy to use the in-vivo approach was Luxturna®. It is administered through a one-time injection into a patient’s eye that replaces the missing genetic material that causes rare forms of inherited vision loss with a synthetic version. The eye is an ideal target for in-vivo therapies, as it is a closed system where the vector can directly reach a relevant number of cells.

In other types of cells, e.g. in organs, delivering the vector into a relevant number of cells is rather difficult. One challenge is that it would be washed off with the flow of blood. In these cases, the patient’s cells are taken out of the body and exposed to the vector in a laboratory. Afterwards, the modified cells are shipped back to the patient and transferred into the body. This approached is called ex-vivo gene therapy.

The first approved gene therapy overall, Glybera® used the ex-vivo approach. The other therapies mentioned above are using the ex-vivo method as well. While Glybera® has been used only once, as it was targeting a very rare condition and carried high cost, the T-cell therapies Kymriah® and Yescarta® are going after much larger markets.

These two therapies have been approved for the treatment of different blood cancers (a certain form of leukaemia and certain form of non-Hodgkin lymphoma). Gene therapy is applied in the following way on the immune cells in both cases:

  1. T-Cells from the patient are collected through a blood draw;
  2. The T-Cells are fitted with a CAR designed to hone in on targets on the surface of cancer cells;
  3. Engineered CAR-T cells are inserted in the blood again;
  4. The CAR directs the cells to the tumor where they can release toxic chemicals and locally kill the cancer cells.
The process of CAR-T cancer therapy

Gene therapies significantly expand the addressable market for medicine. Indeed, Strimvelis® and Luxturna® treat diseases where no other treatment is available, while CAR-T cells have been able to cure some cancer patients for which all other available therapies had failed.

New therapies are in development for hemophilia, immune deficiency, and sickle cell anemia. They have the potential to deliver unprecedented and long-lasting efficacy.

Disease areas where gene therapy can offer a potential “cure”

New estimates expect that peak sales of more than $3.5tn can be generated by addressing these previously untreatable diseases.

Peak sales opportunity for gene therapies

Gene therapies bring with them not only medical advancements that potentially allow us to live longer. They also change the business model of pharmaceutical companies:

  1. From a multi-dose subscription model to a one-time therapy treatment;
  2. From a generic pill that all eligible patients receive to a therapy that is customized for each patient;
  3. From market authorization received after ever larger and longer trials to approval received after small early (phase I/II or phase II) trials;

It is beyond this post to look into what this means for reimbursement, clinical development and supply chain. However, I would like to leave all of you with a thought about this.