Strimvelis "good case study" for Orchard Therapeutics, says CEO
By Simon Wentworth
Orchard Therapeutics (Nasdaq: ORTX) has big ambitions for its role in pioneering some of the most advanced treatments in development today.
Chief executive Mark Rothera says: "We are a publicly-traded, independent company that is carving a path forward for gene therapies."
"Our aspirations are to be global - we're already across Europe and North America - and our aspirations are to be fully integrated: doing our own research, clinical development, manufacturing and commercialization."
The firm is working on ex vivo, autologous, hematopoietic gene therapies.
As Mr Rothera explains: "We're extracting blood stem cells from a patient that has a particular genetic disorder, inserting a working copy of the defective gene into those stem cells, and then reinfusing those gene-modified stem cells back into the patient.
"What happens is those gene-modified stem cells engraft in the bone marrow and that allows them to self perpetuate and provide long-term correction of the disease."
By one estimate, the overall market for gene therapies, while currently small, is expected to grow at a rate of about 30% through to 2025.
It is a growing and increasingly successful area of research which, with the support of important regulatory developments such as Orphan Drug designations in Europe and the USA, could offer companies like Orchard a path to putting breakthrough options in patients’ hands.
GlaxoSmithKline deal
In 2018, the company inked a deal with UK pharma major GlaxoSmithKline (LSE: GSK), to take ownership of its portfolio of approved and investigational rare disease gene therapies. GSK took a 19.9% stake in the company, and a seat on the board.
Among the assets were two late-stage clinical programs in ongoing registrational studies for metachromatic leukodystrophy (MLD) and Wiskott Aldrich syndrome (WAS), and one clinical program for beta thalassemia.
But the headline-grabbing therapy in the deal was Strimvelis, the first autologous ex vivo gene therapy for children with adenosine deaminase severe combined immunodeficiency (ADA-SCID), also known as “bubble boy disease.”
This therapy was approved by the European Medicines Agency in 2016, but despite offering a money-back guarantee, GSK struggled to promote uptake, largely due to the challenges of providing access.
Mr Rothera says the deal "allowed us to go as a company that had two clinical stage programs, to then five clinical stage programs," with another two on the way.
“We've grown very fast, partly as a result of acquiring those GSK assets, and partly through our own academic agreements."
"Now I would say we have one of the most advanced and deep pipelines of gene therapy medicines in the world. So far we have treated more than 150 patients with six rare genetic diseases. We've shown the ability to transform patients in terms of clinical outcomes."
"For everything else we're going to do...you'll have reimbursement locally, in your own country."
As well as making Strimvelis available to patients, he says: "We're learning from it, because this is one of the very few approved ex vivo gene therapy medicines in the world, this was the first, and so for Orchard, as we build ourselves out for the launch of three more programs that we're launching in the next two and a half years, it's actually a very good case study for us about what it means to have patients access treatments of this type."
Orchard has its own candidate in development for bubble boy disease, OTL-101, an ex vivo lentiviral gene therapy which could represent a key step forward in the treatment of the condition.
The Strimvelis program differs from Orchard’s other candidates, in a couple of important ways, he notes.
Firstly, it is an earlier-generation gamma-retroviral vector-based product, whereas the firm's other programs are lentiviral-based.
Secondly, since it is only available in a short window between manufacturing and delivery, the product can only be offered at a specific and highly specialized site in Europe. Patients have to travel to the site, often for weeks or months, for treatment.
This represents a significant hurdle to access, as well as reimbursement headaches. Accessing the therapy for a British patient, for example, involves "persuading the UK NHS to pay for the procedure in Italy. It is more complicated doing it that way, even if you've got a great product."
Orchard aims to overcome this by developing cryogenically-preserved treatments in future, which offers a "far more patient friendly" approach, as the product can be shipped to the patient.
Mr Rothera says: "For everything else we're going to do, it means the patient won't have to travel, and you'll have reimbursement locally, in your own country."
OTL-200
This year, the firm has presented data from OTL-200 in patients with metachromatic leukodystrophy, a rare hereditary disease characterized by accumulation of fats called sulfatides.
This candidate is developed using cryopreservation, with the data showing similar profiles between cryopreserved and fresh formulations.
The data show stable levels of engraftment and reconstitution of enzyme activity in patients, with up to a year of follow-up.
Following the granting of accelerated assessment, Orchard now expects to submit for regulatory approval in Europe in the first half of 2020, and in the USA around one year later
Vinie Varkey, neurology analyst at GlobalData, commented: "With Orchard Therapeutics’ OTL-200 receiving the accelerated assessment, it is now more likely that an effective treatment for metachromatic leukodystrophy (MLD) patients will become available sooner than anticipated," adding: "If OTL-200 is approved in the EU, it will be the first therapy in the market with the potential to cure the disease."
Orchard has been building out its leadership team and constructing a new gene therapy manufacturing facility in Fremont, California, ahead of future approvals and commercialization.
With all the pieces falling into place, patients may have more hope than ever for new and effective treatment options.