Only 2 years after its discovery, the first in the class of small modular immunopharmaceutical (SMIPTM) compounds is set to move forward in a Phase I trial of rheumatoid arthritis (RA), according to Trubion Pharmaceuticals, Inc, of Seattle, Washington.
The company's SMIP agent, TRU-015, an antibody-based designer compound approximately 50% smaller than monoclonal antibodies and capable of rapidly reaching disease target sites more efficiently, may prove to be the first of the small molecule, highly-targeted biologics.
SMIP candidates kill targeted cells through directed action by neutrophils and macrophages, in addition to natural killer cells. TRU-015, an injectable agent, is designed to target and eliminate CD20-bearing B cells, which play a key role in the inflammatory processes of RA, according to Trubion.
Trial details fuzzy
The Phase I trial is a typical dose escalation study and patient size will vary, Daniel J. Burge, MD, Senior Vice President of Clinical Development at Trubion told CIAOMed. "There will be at least a couple of dozen RA patients, but it could be more, and we will look at a wide range of doses to look, first and foremost, at the safety, followed by the pharmacokinetics and the pharmacodynamics," he said.
Dr. Burge emphasized that the completion date for the trial has not yet been determined. "We plan to follow the patients for the duration of B-cell depletion, which is highly variable and may be dependent on the amount of drug that's used," he said.
In vivo studies conducted by Trubion have suggested that TRU-015 depletes B cells more effectively than current products on the market, including rituximab (Rituxan?). "We have some in vitro and animal data and we are very excited about what we are seeing in these models, but the ultimate answer is to progress in the clinic and get to Phase II trials," Dr. Burge said.
"We are very excited about this new platform because we believe it has some distinct advantages over monoclonal antibodies," he continued. "The most clear and obvious distinction is that the SMIPs are smaller and, thus, can provide better tissue penetration of protein, which for certain disease stages can be very important."
Highly tailored approach may be key in RA
"SMIPs allow us to tailor some of the antibody-like functions for specific disease," Dr. Burge said. "If we can determine which functions are important to treat disease and tailor the drug to that particular function, we can have the ability to improve efficacy and eliminate safety concern." In essence, SMIPs can "lessen the activity that may be associated with toxicity in certain monoclonal antibodies," he said.
Although the risk/benefit equation may not be as crucial when treating cancer, Dr. Burge noted that such concerns are of vital importance for patients with RA. "When we are treating cancer, we will use as many tools as possible to kill the cancer cell, but if we are treating RA, safety is a very important factor because it is not imminently life-threatening."
This may be the first such product to enter a Phase I study, but probably not the last, according to Phillip Mease, MD, of Seattle Rheumatology Associates in Seattle, Washington.
"This move to Phase I testing is based on 2 years of experience and it's moving along rapidly," he told CIOAMed, adding that if the trials are successful, TRU-015 will most likely mimic the course of rituximab and seek multiple indications including RA and systemic lupus erythematosus.
SMIP technology will most likely play a role in the future of RA treatment, he says.
Also in the Trubion pipeline is TRU-016, which targets a different B-cell receptor and TRU-017, which targets a non-B-cell receptor for autoimmune applications. In addition, the company is also developing SMIPs that target growth factor receptors, co-stimulatory molecules, members of the tumor necrosis factor (TNF) and TNF-receptor families, as well as specific targets on antigen-presenting cells.
Reference
Trubion Announces Initiation of First Phase I Study in Rheumatoid Arthritis ? SMIPTM
Immunopharmaceuticals To Be Developed for Patient Therapy [press release]. Trubion Pharmaceuticals, Inc; Seattle, Wash. Available at: http://trubion.com/trubion_news_011005.asp. Accessed January 10 9, 2005.