A year after it was hit with a rejection from the FDA, Citius Pharmaceuticals has won over the U.S. regulator, scoring an approval for Lymphir (denileukin diftitox-cxdl) to treat relapsed or refractory cutaneous T-cell lymphoma (CTCL) in patients who've tried at least one prior systemic therapy.
Lymphir becomes the first treatment in the indication to specifically target the interleukin-2 (IL-2) receptor found on malignant T-cells and regulatory T-cells (Tregs). It also is the first FDA-approved product for the 17-year-old New Jersey company, which expects to launch Lymphir within the next five months.
Lymphir is a revamped version of Eisai’s CTCL treatment Ontak, which was on the market from 1999 to 2014. The Japanese company withdrew the product in 2014 because of manufacturing issues related to its bacterial expression.
After a more purified formulation of Ontak was developed to address those manufacturing shortfalls, Eisai sold its rights outside of Asia to Dr. Reddy’s Laboratories. Then in 2021, the Indian company flipped Lymphir to Citius for $40 million up front, with an additional $40 million due upon FDA approval.
Citius appeared on the verge of an FDA nod last summer before the agency sent the company a complete response letter (CRL), asking for enhanced product testing and “additional controls,” that the agency had previously requested during its review. There were no efficacy or safety issues identified in the CRL.
“The introduction of Lymphir, with its potential to rapidly reduce skin disease and control symptomatic itching without cumulative toxicity, is expected to expand the CTCL treatment landscape and grow the overall market, currently estimated to be $300 to $400 million,” Leonard Mazur, the CEO of Citius, said in a release.
Citius did not reveal a price for Lymphir. The company said in an email that the price is "expected to be in line with other systemic therapies for CTCL."
CTCL is a non-Hodgkin lymphoma that primarily affects the skin. CTCL is the more prevalent type of two forms of cutaneous lymphoma, as it develops in the T-lymphocytes (T-cells) versus the B-lymphocytes.
It causes red, scaly, itchy patches on the skin and is often misdiagnosed as eczema. It strikes twice as many men as women, with most diagnosed with the condition after age 50. Aside from allogenic stem cell transplantation—for which only a few can qualify—there is no curative therapy.
A minority of people with CTCL develop advanced disease, with tumor formation, ulceration and involvement of the lymph nodes, blood, and internal organs. Most people with CTCL have a slow-growing form of the disorder which is treatable and usually not life-threatening.
There are roughly 3,000 new cases each year in the US, with between 30,000 and 40,000 living with the disease.
“We believe Lymphir’s unique IL-2 receptor-targeted treatment, which kills tumor cells directly, and concurrently depletes host Tregs in order to boost the body’s immune response, is an important differentiator and offers clinically meaningful benefits to a significant percentage of (relapsed and refractory) patients,” Myron Czuczman, the chief medical officer of Citius, said.
The approval is backed by a phase 3 trial which showed that Lymphir provided a complete or partial response in 36% of patients and reduced skin disease issues in 84%. The median response time was 1.4 months, with 70% of responders seeing results after one or two treatment cycles.