Source – Citius Pharmaceuticals
The FDA has declined Citius Pharmaceuticals’ request to market Lymphir, an updated version of a lymphoma therapy that was withdrawn from the market a few years ago.
Citius clarified that the FDA’s complete response letter (CRL) for Lymphir (denileukin diftitox) was not due to any concerns about the drug’s effectiveness or safety, nor was it related to the proposed prescribing information. Instead, the rejection was primarily because the application lacked “enhanced product testing,” which the FDA had previously requested. Citius’ CEO, Leonard Mazur, stated that the company plans to submit the required data and is actively working with the FDA to obtain approval.
Lymphir is a recombinant fusion protein that combines an IL-2 binding domain with diphtheria toxin fragments. Its purpose is to bind to and eliminate leukemia cells. Citius is seeking approval in the US to use Lymphir as a treatment for patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL), which is a form of non-Hodgkin lymphoma, after they have undergone at least one prior systemic therapy.
This new version of Lymphir is a purified and reformulated version of Eisai’s Ontak. Ontak was initially approved by the FDA in 1999 and received approval for the CTCL indication in 2008. However, it was later withdrawn from the market in 2014 due to manufacturing issues, including problems with the purity of the recombinant protein in the drug.
In 2016, Eisai licensed the drug, along with its reformulation, to the US subsidiary of Indian drugmaker Dr Reddy’s Laboratories. Dr Reddy’s subsequently sold the rights to Citius in 2021, except for some Asian markets like Japan, which remained under Eisai’s control. The deal involved an upfront payment of $40 million and an additional $70 million tied to development and regulatory milestones.
A Phase III clinical trial for Lymphir, demonstrating results consistent with the earlier formulation, was completed at the end of 2021, showing an objective response rate of 36%. A biologics license application for CTCL was submitted in the third quarter of 2022.
Eisai obtained Japanese approval for the new version of Lymphir under the name Remitoro in March 2021, for both CTCL and peripheral T-cell lymphoma (PTCL), based on a mid-stage study carried out in Japanese patients. The study revealed a response rate of around 32% for CTCL and 41% for PTCL.
The FDA granted orphan-drug designations for Lymphir for PTCL in 2011 and CTCL in 2013. Additionally, Lymphir is being studied in investigator-led trials for solid tumors, both in combination with Merck & Co’s cancer immunotherapy Keytruda (pembrolizumab) and as a pre-treatment before lymphodepletion and CAR-T therapy for patients with B-cell lymphomas.
“We appreciate the FDA’s expeditious review of our application. We intend to provide additional data and remain fully engaged with the FDA as we continue to work toward approval. We remain confident in the potential of LYMPHIR to become an important addition to the treatment landscape for patients with relapsed or refractory CTCL and make a meaningful difference in their lives.”
– Leonard Mazur, Chairman and CEO of Citius.
Citius has projected the market opportunity for CTCL to be around $300 to $400 million, with even greater potential in PTCL and immuno-oncology indications.
Apart from Lymphir, Citius is also developing Mino-Lok, an antibiotic therapy for catheter- and central line-related bloodstream infections (CRBSI/CLABSI), with Phase III results expected soon. Additionally, they are working on a topical formulation of halobetasol and lidocaine in Phase IIb, aiming to become the first FDA-approved therapy for hemorrhoids.
