Nearly 50% of the children diagnosed with neuroblastoma are considered high-risk, where the tumor has spread, making surgery no longer a viable treatment option. Owing to this stark statistic, the disease is quite difficult to treat. But there might be light at the end of the tunnel. U.K.-based Renaissance Pharma’s drug candidate, which has shown promise during clinical trials, aims to take on the disease.
Neuroblastoma is a rare children’s cancer that affects around 700 kids in the U.S. alone, and 90% of the patients are under the age of five. Although children with a family history of neuroblastoma are more likely to develop it, most cases occur sporadically. It happens when nerve tissues that aren’t fully developed – called neuroblasts – grow out of control, often due to a genetic mutation. The continuous proliferation of these cells results in the formation of a tumor.
Current treatment approaches that aim to kill the tumor include surgery, chemotherapy and radiation therapy. However, because most cases are detected once tumors have spread to a point where it compresses nearby organs, children often have to undergo multiple cycles of these treatments – which takes a toll on the patient.
“These are children that have gone through high dose chemotherapy, stem cell transplantation, radiation, surgery. I mean, this is a brutal, brutal course of treatment,” said Simon Ball, chief executive officer (CEO) of Renaissance Pharma, a startup that is looking to change pediatric cancer care with its novel drug candidate.
Launched a little over a week ago, Renaissance Pharma is co-founded by Ball and chairman Lee Morley, former CEO of EUSA Pharma. The company’s drug candidate Hu14.18, which is in clinical stages, is one of the few anti-GD2 monoclonal antibodies that have been developed. The GD2 antigen is highly expressed in neuroblastoma tumors, making it a promising drug target.
A therapy like no other?
Unlike chimeric anti-GD2 antibodies such as the U.S.-based United Therapeutics’ Unituxin and British biotech company EUSA Pharma’s Qarziba, Hu14.18 is a humanized one – these carry a lower risk of immunogenicity when compared to chimeric antibodies.
Moreover, both Unituxin and Qarziba are offered as a second line of treatment when initial treatment has failed or is no longer effective, and the latter, typically when patients have undergone courses of chemotherapy – which achieved at least a partial response – myeloablative therapy and stem cell transplantation.
The only humanized anti-GD2 monoclonal antibody in the market at present, is American biotech Y-mAbs Therapeutics’ Danyelza, which is prescribed only in cases of refractory and relapsed forms of the disease. This leaves a huge gap in the market for GD-2 targeting therapies in the induction phase of cancer treatment.
Renaissance Pharma’s Hu14.18 is designed to bind to the surface of neuroblastoma tumor cells. The binding rallies immune cells to kill tumor cells, according to Ball. What makes the potential drug one of a kind is that it has been engineered to reduce dose-limiting pain and certain other side effects. This is because the drug is produced with a point mutation that reduces complement activation – a central process in the immune system – thereby minimizing pain caused by the antibody binding to peripheral nerves. This, in turn, enables higher antibody dosing. To add to that, to enhance its potential to destroy the tumor, the drug is derived from a cell line which can amplify cell kill activity.
“There is nothing out there right now, from a GD2 antibody perspective, that’s got any data in the induction setting. And that’s why this is so exciting for us,” said Ball.
Hu14.18 makes strides in clinical trials
The pediatrics company, which signed an exclusive license agreement with St. Jude Children’s Research Hospital in the U.S. to secure development, manufacturing and commercialisation rights for Hu14.18, had conducted a phase 2 trial, which reaped positive results. For the study, 64 patients were given chemotherapy drugs busulfan and melphalan – over six cycles – along with Hu14.18, as part of the induction phase, after which, they received radiation therapy and further immunotherapy.
It was found that after the first two cycles of the co-administered chemotherapy and immunotherapy, in 42 of the patients, a 75% reduction in tumor was observed. At the end of three years post treatment, a 73.7% event-free survival – meaning that either the tumor had not reappeared or grown – and an overall survival rate of 86% was achieved. On top of that, the regimen was well-tolerated, and a larger trial could validate the safety and efficacy of the drug.
Could Renaissance Pharma’s drug candidate spur a shift in the standard of care?
What makes these results particularly striking is that, in newly-diagnosed high risk neuroblastoma patients, the average overall survival rate is 50%, compared to Hu14.18’s encouraging 86%.
“The reason it looks so impressive is that the eligibility criteria for the phase 2 was really arriving in the carpark of St. Jude. And being diagnosed across international qualification in regard to having a high risk neuroblastoma diagnosis. if that was the case, you’re accepted onto the trial. And miraculously, 86% of those children were still alive after three years, which is phenomenal,” said Ball.
He explained that if we compared the current standards of care in the U.S. and Europe, where anti-GD2-based therapies are introduced only in subsequent courses of treatment, and not during the initial stages, to Hu14.18’s progress in trials, there is a remarkable difference, particularly with regard to the overall survival rate.
“The generally accepted overall survival statistic is about 50%. So there’s not a head-to-head comparison. And that’s really important for us all to understand that there is an 86% overall survival benefit associated with the product that we have licensed,” said Ball.
“When we look at that differential, that makes us very excited about the prospect of this having a potential to change the standard of care. And it really puts a responsibility on the shoulders of Renaissance Pharma to get this product to market as swiftly as possible, through interactions with the different agencies so that children can reap the benefit of this data.”
Next steps for Renaissance Pharma
Funded by private investors, the startup looks to get in touch with the U.S. Food and Drug Administration (FDA), the European Union’s European Medicines Agency (EMA), and other international regulatory bodies soon, to expedite the manufacture and commercialization of the drug.
“It’s not beyond the realms of possibility that there may be a more accelerated route for us here, given the strength of the survival data,” commented Ball.
“Our real priority here is to get in front of these agencies to talk to them about the data, to show that phase two was undertaken in an incredibly professional manner. The reputation of St. Jude was earned through many years, since the 1960s, and has done tremendous research. And this is another example of a very well-executed phase two from St. Jude. So, we have to represent that data as best as we possibly can,” he said. “The outcome of these agency meetings will be educational for us, and will drive us down a certain pathway.”
With the possible approval from these agencies, the company will be able to sell the drug in the U.S., Canada, Europe, China, Japan and Turkey. And, at present, the company awaits the results for the four-year, as well as five-year, overall survival rate, having obtained favorable three-year overall survival data.
“What we hope is the benefit, it’s the chance of life, for an incremental three out of 10 children that are diagnosed, relative to today’s setting. We’re looking to try and make a difference with the next generation of therapeutics in the pediatric rare disease space with a particular bent on oncology.”