Iplex™
Insmed maintains a propriety protein platform, based on the FDA-approved IPLEX™, as a development candidate for the treatment of neuromuscular and metabolic disorders. Insmed's proprietary pipeline using the IPLEX™ protein platform includes a treatment for myotonic muscular dystrophy (MMD), which was given an orphan drug designation by the FDA. In this indication, Insmed has completed a double-blind, placebo controlled phase II study. In addition, Insmed has an expanded access program for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, in Italy. And finally, Insmed has early stage research programs investigating retinopathy of prematurity (ROP) and HIV Adipose Redistribution Syndrome (HARS).
Myotonic Muscular Dystrophy (MMD) is the most common form of adult muscular dystrophy, affecting approximately 37,000 Americans, and nearly 60,000 people in the European Union. MMD is a genetic disease characterized by endurance loss, muscle wasting, weakness, pain, cognitive impairment and gastro-intestinal dysfunction. There is currently no cure for the disease, and no specific treatment has been developed to satisfactorily reverse or ameliorate the common symptoms associated with the disease.
With funding provided by the Muscular Dystrophy Association and the National Institutes of Health, Insmed conducted a randomized, placebo-controlled, double-blind clinical study in 60 patients with MMD. This phase II program is studying the safety and tolerability of once-daily, subcutaneous injection of IPLEX™. On June 25, 2009 Insmed reported that the results of the trial indicated that IPLEX™ did not exhibit a statistically significant improvement in the functional measure of endurance by the six-minute walk test, muscle function, muscle strength, or quality of life in any of the tests utilized in this study. Based on the limited number of subjects enrolled with significant impairments in cognitive function, gastrointestinal function or pain, Insmed was unable to reach any conclusions regarding the effects of IPLEX™ on these endpoints.
IPLEX™ did, however, demonstrate improvements in standard measures of insulin sensitivity and reductions in fasting glucose, fasting insulin, cholesterol and triglycerides, which is consistent with the expected metabolic profile of insulin-like growth factor. Administration of IPLEX™ also resulted in anabolic effects of increased body mass index and higher levels of testosterone. The drug was well tolerated in MMD subjects and demonstrated a safety profile consistent with previous studies of IPLEX™.
Based on the metabolic improvements observed in patients treated with IPLEX™ in this trial, and discussions with key opinion leaders, the Company intends to apply for a grant from the Muscular Dystrophy Association ("MDA") to facilitate an additional Phase II trial focused solely on a subset of MMD patients with severe insulin resistance who, based on the results of this trial, may be more likely to benefit from IPLEX™ treatment. Alternative methods of assessing muscle function will be considered for the proposed trial.
Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's Disease is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed.
In January 2007, we announced that the Italian Ministry of Health requested
Insmed to make IPLEX™ available to treat Italian patients suffering
from ALS and we are currently supplying IPLEX™ to these patients under
an expanded access program. In Italy it is estimated that 1,000 new cases
of ALS are diagnosed every year. A summary of the Italian experience through February 2009 is provided here.
On November 10, 2008 Insmed announced that Genentech, Ipsen/Tercica and Insmed jointly issued the following statement: “Genentech, Ipsen/Tercica, and Insmed have been contacted by people living with Amyotrophic Lateral Sclerosis (ALS) and their loved ones seeking access to an IGF-I/IGFBP3 product called IPLEX™, which is solely manufactured by Insmed. We understand the devastation a disease like ALS causes and that there are a lack of available therapies that provide meaningful clinical benefit. Although IPLEX™ has not been rigorously tested in people with ALS, nor received regulatory approval for use in ALS, all the companies involved appreciate the urgency and desperation for new treatments in the ALS community. We are all working diligently to determine how best to respond to that need. The availability of IPLEX™ is subject to a Court-Ordered Settlement Agreement. On November 8, 2008, Genentech and Ipsen/Tercica signed a letter of intent whereby they have consented to amend the Court-Ordered Settlement Agreement to permit Insmed to supply IPLEX™ in connection with named-patient ALS programs worldwide on a royalty-free basis. Insmed’s ability to do so will be dependent on satisfying any regulatory requirements in any country where a request for treatment is made. Ipsen/Tercica and Insmed also plan to enter into negotiations concerning the development of IPLEX™ for the treatment of ALS, subject to analyzing the data from the ALS patients in Italy who have received IPLEX™, and satisfying any applicable regulatory requirements. These actions represent each company’s commitment to find a solution to the requests coming from the community of patients and their families. Insmed will update the community as further progress is made.”
On March 10, 2009 Insmed and the U.S. Food and Drug Administration (FDA) separately issued statements on their websites regarding the future use of IPLEX™ in patients with ALS. Because of the limited supply of IPLEX™ currently available, both parties agreed that the drug will be made available through two investigational avenues:
- Single-patient US INDs requesting "compassionate use" of IPLEX™ for treatment of named patients with ALS that were received and date-stamped by FDA's document room by close of business on March 6, 2009 will be allowed to proceed.
- Insmed will sponsor an ALS clinical trial in the United States. The clinical trial is under development and will provide patients with ALS who are interested in receiving IPLEX™ treatment the opportunity to be randomly assigned to receive drug through a lottery system.
All patients who receive IPLEX™ under a single patient IND or in the Insmed clinical trial must be adequately informed by their treating physician of the possible risks of the treatment.
As of May 2009, all patients authorized for compassionate use treatment under single-patient INDs have been supplied with IPLEX™.
With regard to the upcoming clinical trial, Insmed is working with the FDA to make the necessary preparations. The initiation of any clinical trial requires extensive work under any circumstances. In this case, there are added complexities due to the interest in establishing a lottery system that can accommodate ALS patients throughout the country, regardless of geographic location. We understand that time is of the essence given the nature of this disease, and we are committed to meeting all regulatory requirements in as efficient a manner as is achievable so that the trial can start as soon as possible.
We anticipate that patients will be randomized into the trial through a lottery, with the lottery managed by an independent party. When additional information is available, we will provide the appropriate specifics concerning the lottery system, including when and how a patient can formalize his or her interest in the trial.
Please note that declarations of interest made directly to Insmed will not be recorded and/or archived at this or any point in time, as the independent party supervising the lottery will be responsible for capturing all the necessary information from interested patients. The period for declaring interest will span several weeks to allow adequate time for patients to register their interest. No additional details about the lottery are available at this time, but please continue to check our website periodically.
We recognize the tremendous patient interest in IPLEX™ and intend to remain transparent in our actions as we build the program necessary to address patient needs.
Regarding the Insmed clinical trial, contact Insmed at (804) 565-3083 or iplex_als@insmed.com.
The FDA statement regarding access to IPLEX can be found at http://www.fda.gov/Drugs/ResourcesForYou/HealthProfessionals/ucm118117.htm
