The US Food and Drug Administration (FDA) has granted fast track designation to dilanubicel (NLA101) for use in patients with high-risk hematologic malignancies receiving an allogeneic cord blood transplant.
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 transplant 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.
Dilanubicel also has orphan drug designation from the FDA.
About fast track, orphan designations
The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.
Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.
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.
Trials of dilanubicel
The fast track and orphan designations for dilanubicel were 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 transplant protocol, minus dilanubicel.
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 (87% and 66%, respectively).
Dilanubicel is currently under investigation in a phase 2b trial (NCT01690520) that 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.