The US Food and Drug Administration (FDA) has granted orphan drug designation to dilanubicel (NLA101) for the reduction of morbidity and mortality associated with hematopoietic stem cell transplant (HSCT).
Dilanubicel is a universal-donor, ex-vivo-expanded hematopoietic stem and progenitor cell product.
It is intended to induce short-term hematopoiesis, which lasts until a patient’s immune system recovers.
However, dilanubicel may also produce long-term immunologic benefits and could potentially improve survival in HSCT recipients, according to Nohla Therapeutics, the company developing the product.
Dilanubicel is manufactured ahead of time, cryopreserved, and intended for immediate off-the-shelf use.
Phase 2 trials
The orphan drug designation for dilanubicel was supported by data from a phase 2, single-center study. Results from this study were presented in a poster at the 23rd Congress of European Hematology Association (EHA) in June.
The trial included 15 patients with hematologic malignancies who underwent a cord blood transplant. Conditioning consisted of fludarabine (75 mg/m2), cyclophosphamide (120 mg/kg), and total body irradiation (13.2 Gy).
Patients received unmanipulated cord blood unit(s), followed 4 hours later by dilanubicel infusion. Prophylaxis for graft-vs-host disease (GVHD) was cyclosporine/mycophenolate mofetil.
The researchers compared outcomes in the 15 dilanubicel recipients to outcomes in a concurrent control cohort of 50 patients treated with the same HSCT protocol, minus dilanubicel. There were no significant differences between the 2 cohorts with regard to baseline characteristics.
The time to neutrophil and platelet recovery were both significantly better in dilanubicel recipients than controls.
At day 100, the cumulative incidence of neutrophil recovery was 100% in dilanubicel recipients and 94% in controls (P=0.005). The median time to neutrophil recovery was 19 days (range, 9-31) and 25 days (range, 14-45), respectively.
The cumulative incidence of platelet recovery was 93% in dilanubicel recipients and 74% in controls (P=0.02). The median time to platelet recovery was 35 days (range, 21-86) and 48 days (range, 24-158), respectively.
At 100 days, there were no cases of grade 3-4 acute GVHD in dilanubicel recipients, but the incidence of grade 3-4 acute GVHD was 29% in the control group.
At 5 years, 27% of dilanubicel recipients had experienced chronic GVHD, compared to 38% of the control group.
There were no cases of transplant related mortality (TRM) in dilanubicel recipients, but the rate of TRM was 16% in the control group.
Two dilanubicel recipients (13%) relapsed post-transplant and subsequently died.
The 5-year disease-free survival rate was 87% in dilanubicel recipients and 66% in the control group. Overall survival rates were the same.
“Dilanubicel has shown encouraging initial activity as a novel cell therapy in patients with hematologic malignancies receiving a cord blood transplant,” said President and CEO of Nohla Therapeutics Katie Fanning.
“We believe the addition of dilanubicel has the potential to make a meaningful difference for these patients, and we look forward to having the top-line results from the fully enrolled, randomized, phase 2b trial later this year.”
The phase 2b trial (NCT01690520) has enrolled 160 patients with hematologic malignancies. The goal of the trial is to determine whether adding dilanubicel to standard donor cord blood transplant decreases the time to hematopoietic recovery, thereby reducing associated morbidities and mortality.
Another phase 2 trial, called LAUNCH (NCT03301597), is currently enrolling patients who have acute myeloid leukemia and chemotherapy-induced myelosuppression. The goals of this trial are to evaluate dilanubicel’s ability to reduce the rate of grade 3 or higher infections associated with chemotherapy-induced neutropenia and to identify the lowest effective cell dose of dilanubicel.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.