Just a few months ago the commercialisation of gene therapies in serious numbers seemed a distant prospect despite decades of research and promise - how quickly things change.
Gene therapy typically involves one of three approaches - replacing mutant or absent genes with healthy ones, changing the way genes are regulated to restore functionality, or using gene therapy to alter the function of entirely different genes.
The FDA recently said it expects to be approving around 20 gene and cell therapies per year by the middle of next decade and now new data released by the Alliance for Regenerative Medicine (ARM) and US-based publication GEN has provided further evidence of how quickly these technologies are emerging from company pipelines.
ARM is a US-based international organisation of small and large companies, not-for-profit research institutions, patient organisations and other sector stakeholders focused on bringing regenerative medicine to patients globally.
The organisation has partnered with GEN to release of information on what it describes as the 25 'up-and-coming' gene therapies - therapies making the list are currently in late-stage trials or already in the process of being commercialised.
Some of the therapies even work by harnessing the combined power of gene therapy and cancer treating immunotherapy.
The list includes a small number of therapies belonging to well-known global biopharmaceutical companies but the majority are being developed by small to mid-size companies
The companies are headquartered in the US, Europe, South Korea and China - no Australian companies make the list.
Many of the 25 gene therapies are in the process of being commercialised in the US and Europe but the small to medium companies have no current disclosed plans to commercialise their technologies in Australia.
BiotechDispatch has previously reported on two gene therapies that have already gained regulatory approval overseas. They are high-cost but potentially curative following one-time administration.
The US FDA approved Novartis' (AveXis) ZOLGENSMA (onasemnogene abeparvovec-xioi) earlier this year for spinal muscular atrophy. It is on ARM's list of 25 and the company says it will bring the therapy to Australia.
The company's long-term established local presence creates a bridge for ZOLGENSMA into Australia - yet this could be the exception.
bluebird bio's ZYNTEGLO (autologous CD34+ cells encoding βA-T87Q-globin gene) for transfusion-dependent beta-thalassemia is also on the list. It recently secured approval in Europe. The company has extensive plans to commercialise ZYNTEGLO throughout Europe and the US. It has not yet disclosed plans to bring any of its gene therapies to Australia.
ZYNTEGLO is also in late-stage development for sickle cell disease. The company's LENTI-D is also on the list of 25.
The FDA has granted LENTI-D 'breakthrough therapy designation' for the treatment of cerebral adrenoleukodystrophy (CALD). CALD is a rare, serious and life-threatening hereditary neurological disorder.
Four of the 25 gene therapies on the ARM list are for haemophilia and seek to address the underlying cause of the hereditary diseases.
BioMarin's valoctocogene roxaparvovec and Spark Therapeutics' SPK-8011 are in development for haemophilia A. uniQure's AMT-061 and Pfizer's fidanacogene elaparvovec are in development for haemophilia B.
Pfizer has been developing fidanacogene elaparvovec in collaboration with Spark Therapeutics. Pfizer launched the phase 3 program for fidanacogene elaparvovec and gained rights to Spark's full haemophilia B program before Roche announced its planned acquisition of the gene therapy company earlier this year.
Six of the 25 gene therapies on the ARM list are for the treatment of cancer.
Gene therapies can be used in several different ways when it comes to the treatment of cancer. These include genetically engineered viruses that directly kill cancer cells and gene transfer to alter the abnormal functioning of cancer cells. It also includes immunotherapy, incorporating CAR T-cell therapy, targeting and killing tumour cells as well as 'suicide transgenes'.
One of the therapies involves a partnership between Oxford University spin-out Oxford BioMedica (OXB) and Sanofi.
They are collaborating on the development of TROVAC (OXB-301) for ovarian and colorectal cancers. It is a therapeutic vaccine that stimulates the immune system to destroy cancer cells expressing the 5T4 tumour antigen that is present in most solid tumours.
OXB was behind the development of Novartis CAR-T KYMRIAH. In 2014, Novartis signed a deal for an exclusive licence for the worldwide development and commercialisation of all CAR-T cell products produced by OXB's LENTIVECTOR platform.
Another gene therapy in development includes a cross-continental collaboration involving South Korean companies SillJen and GC Pharma, French company Transgene and Chinese companies Beijing Shenogen Pharma Group and Lee's Pharmaceutical. They are developing PEXA-VEC for liver cancer. It is a vaccine virus engineered to directly kill tumour cells and stimulate anti-tumour immunity.
US company Advantagene is developing PROSTATAK (AdV-tk + valacyclovir) for the treatment of prostate cancer. It works by gene-mediated cytotoxic immunotherapy - an approach that uses gene therapy to generate a tumour-specific vaccine.
Other companies with gene therapies on the list include Tocagene with ApolloBio, VBL Therapeutics, GensightBiologics, Angionetics, Huapont Life Sciences, FKD Therapies with Ferring Pharmaceuticals, Lysogene with Regenxbio and Sarepta Therapeutics, Evevance Pharmaceuticals with OcuNexus Therapeutics, Nightstar Therapeutics, Renovo Therapeutics, Inovio Pharmaceuticals together with ApolloBio and ViroMed, Bejing together with Nuosilandi Biotechnology, and Reyon Pharmaceuticals.
Dr Amanda Ruth (amanda@dailydispatch.com.au)