ICER Gives Cell Therapy for Post-Transplant Complications High Rating

If priced between $143,900 and $273,700 per treatment cycle, tabelecleucel (tab-cel) would be a cost-effective cell therapy to treat a post-transplant complication, according to an evidence report from The Institute for Clinical and Economic Review. Tab-cel is currently being reviewed by U.S. regulators to treat adult and pediatric patients two years of age and older with Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD).

Lymphoproliferative disease is a rare but life-threatening complication after organ or stem-cell transplants. Many cases are associated with Epstein-Barr virus, accounting for more than 75% of post-transplant lymphoproliferative disease, according to one estimate. Most people have been exposed to Epstein-Barr, but the immune suppression drugs used after a transplant can reactivate the virus.

There is no treatment available specifically for Epstein-Barr virus related post-transplant lymphoproliferative disease, but Rituxan (rituximab) and chemotherapy are often used to treat the disease.

Foluso Agboola

“EBV+ PTLD is a rare and often fatal cancer associated with solid organ transplant and stem cell transplant,” ICER’s vice president of research Foluso Agboola, MBBS, MPH, said in a news release. “Unfortunately, approximately half of EBV+ PTLD cases are refractory to initial treatment or relapse, resulting in a poor prognosis. The limited evidence on tabelecleucel suggests that it provides important clinical benefits in patients with relapsed refractory EBV+ PTLD, extending survival for patients who otherwise do not usually survive beyond a few weeks to months, with few harms.”

Tab-cel is an allogeneic, T-cell immunotherapy that, if approved, would administered intravenously for three doses per cycle for a minimum of two cycles. It would be available as an off-the- shelf, T-cell therapy.

The biologics license application for tab-cel is being review by U.S. regulators, and an FDA decision is expected by Jan. 15, 2025. Developed by Atara Biotherapeutics, tab-cel will be marketed in the United States by Pierre Fabre Laboratories, according an agreement between the companies in December 2023. Based on this agreement, all tab-cel manufacturing, clinical, and regulatory activities have been transitioned from Atara to Pierre Fabre Laboratories.

Tab-cel is available in Europe with the brand name Ebvallo and marketed by Pierre Fabre.

ICER has given tabelecleucel a rating of A, indicating the T cell therapy has a high certainty of substantial net health benefit. The analysis indicates that treatment with tab-cel extends survival for patients who otherwise do not usually survive beyond a few weeks to months. The data indicate that the therapy appears to induce partial or complete remission in a substantial proportion of patients with relapsed/refractory Epstein-Barr virus positive post-transplant lymphoproliferative disease.

ICER’s health-benefit price benchmark is a price range suggesting the highest U.S. price, net of rebates and discounts, a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment.

The BLA is supported by data from more than 43 patients treated with tab-cel across multiple life-threatening diseases, including the single-arm ALLELE study that met its primary endpoint. Interim data from this study found that 22 of 43 (51.2%) Epstein-Barr virus related post-transplant lymphoproliferative disease patients achieved an objective response rate. The median duration of response was 23 months, and the median overall survival was 18.4 months.

In ICER’s analysis, tab-cel resulted in high quality of life years (QALY), equal value of life years (evLY) gained, and life years gained over a lifetime horizon. Based on a placeholder price of $287,500 per 35-day treatment cycle, the incremental cost-effectiveness of tabelecleucel was approximately $183,449 per QALY gained and $156,668 per evLY gained.

Because tab-cel is an off-the-shelf product, the ability to treat patients early would be an advantage, ICER notes. Currently available T cell therapies have lengthy manufacturing times, which can delay treatment.

ICER officials, however, cautioned that the cost-effectiveness findings could be an optimistic estimate given the limited clinical evidence available. The actual cost-effectiveness will be dependent on its actual price and the survival benefit of treatment. The analysis notes that few patients have been treated have been followed for five years.

“Additionally, it is not clear how generalizable the data from the ALLELE study are, since the small sample size and short duration of the trial may obscure differences in treatment effect by transplant type,” the reported noted.

Long-term safety data are also needed to assess potential harms. ICER officials noted there were four events of acute graft versus host disease (GvHD) in three patients reported in the U.S. expanded access program that were considered by investigators to be possibly related to tabelecleucel.