With positive phase II data in its possession, Kiadis Pharma (OTC:KIADF) next year plans to submit its anti-graft rejection treatment Atir101 for conditional EU approval. However, the Netherlands-based group knows it has competition from old-fashioned chemotherapy.
A planned pivotal trial will pit Atir101, against the Baltimore protocol, which depletes alloreactive T cells after transplantation using cyclophosphamide. In contrast Atir101 uses T cells manipulated to avoid the problem of graft-vs-host disease in leukemia patients receiving a partially matched bone marrow transplant. Kiadis' chief executive, Manfred Rüdiger is willing to admit the rival treatment “is cheap, and it is effective". However, he believes that a higher rate of relapses and graft vs host with the Baltimore protocol will win the day for Atir101.
Atir101 aims to solve a problem in treating leukemia – how to provide hematopoietic stem cell transplantation to patients who cannot find a donor with a matching human leukocyte antigen profile to avert graft-vs-host disease (GvHD). If GvHD can be averted, the 35% of patients eligible for transplantation but who cannot find a match could receive a transplant.
Kiadis’ technology consists of an infusion of donor T cells that have been depleted of any that would react to foreign tissue in the patient’s body. Rather than undergoing immunosuppressive treatment, these patients will have a functioning immune response that can fight infections and also detect and eliminate residual tumor cells.
The phase II trial being used for European submission found that none of the 23 patients suffered grade III or IV GvHD, and only three suffered grade II at the six-month analysis. There were three cases of transplant-related mortality (TRM), a 23% rate that served as the primary endpoint, and a fourth patient died from relapse, giving an overall survival rate of 83%.
Compared against historical controls, this represents a significant reduction in TRM and improvement in overall survival.
At Ash the group presented data at 12 months, which confirmed the continuing low rate of GvHD, along with a total of seven cases of TRM and two deaths from disease relapse, resulting in a 30% TRM rate and 61% overall survival.
Mr Rüdiger says that for conditional approval – which could realistically come in 2018 – the EMA will accept data comparing Atir101 against historical controls, although a randomized controlled trial will be necessary for full approval.
If it does achieve conditional approval in 2018, it will trail MolMed's Zalmoxis by about two years and could be on a similar schedule as Bellicum's BPX-501; both of these are engineered T cells that are sensitive to destruction by drugs if GvHD occurs (Quiet revolution gets under way in stem cell transplantation, August 5, 2016). The US FDA is asking for a randomized controlled trial, however, which Kiadis wants to start next year.
Atir101 versus Baltimore
This is where the comparison versus the Baltimore protocol will be important, as this will be the pivotal trial's control arm. Based on a review of literature, the company says the Baltimore protocol has achieved a similar overall survival rate at 12 months, 65%, but with a higher relapse mortality and GvHD rate balanced by lower non-relapse mortality.
Kiadis had not tested Atir101 against the Baltimore protocol earlier because this was only seen as an “emerging therapy”, but is now seen as a standard of care. Thus, the pivotal trial will enrol 200 patients randomized 1:1 to either treatment, with the primary endpoint of event-free survival – consisting of survival without either GVHD or relapse.
A successful outcome could see US launch by 2021, Mr Rüdiger says, in which case Kiadis would hope to find a partner with US commercial strength. In the EU, he believes that the group could launch unpartnered. Kiadis raised €34.7 ($37.2m) in a 2015 IPO, and had €23.7m at June 30.
The company is comfortable with its clinical expertise, but if it were to seek to partner in Europe this would need to bring know-how in market access and reimbursement. “If we partner it has to add value. We are opportunistic in that sense,” he says.
The group has not said publicly what it would charge for Atir101. However, for comparison purposes, Mr Rüdiger says the baseline cost of using a matched family member as donor is €150,000-160,000 in the first year. Going to a registry adds €30,000, and using umbilical cord blood adds €100,000-€120,000, and of course with a low GVHD rate Atir101 saves treatment costs.
“We are definitely €100,000 cheaper,” he says. “If we are at €100K or more, we should be in the sweet spot. It’s very justifiable when you compare it to the costs of kinase inhibitors or monoclonal antibodies.”