The Journey

Read this post on a diferent forum and thought I should post it here. This letter was sent by Ron Gunn at INSMED who controll the IPLEX trial in Italy. INSMED Company Statement Regarding IPLEX™ (rhIGF-I/rhIGFBP-3) ALS Expanded Access Treatment Program in Italy This Company Statement is intended to communicate the activities of our ongoing IPLEXTM Expanded Access Treatment Program (EAP) for patients with Amyotrophic Lateral Sclerosis (ALS) in Italy. IPLEX (rhIGF-I/rhIGFBP-3) IPLEX is the trademark for the drug known as rhIGF-I/rhIGFBP-3. IPLEX is a synthetic complex of the growth factor, insulin like growth factor-I also known as IGF-I and the major protein in the bloodstream, IGFBP-3, which regulates the actions of IGF-I. IPLEX was approved by the US Food and Drug Administration in 2005 for a rare growth disorder unrelated to ALS. Until the initiation of the EAP, IPLEX had never been investigated for the treatment of ALS. ALS, often referred to as Lou Gehrig’s disease, is a progressive neurodegenerative disorder that affects nerve cells in the brain and 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 movement action progressively affected patients in the later stage of the disease may become totally paralyzed. IGF-I is a neurotrophic factor which has been shown to be essential for normal development of the nervous system. In animal models, IGF-I has been shown to protect motor neurons from injury and promote muscle and nerve regeneration. IGF-I has been studied as a potential treatment for patients with ALS over the last decade. Two randomized controlled trials have been conducted with a product known as MyotrophinTM which is a synthetic version of IGF-I. The larger trial showed slowing of the progression of functional impairment and improvements in quality of life. The second, smaller trial, showed similar trends but these trends did not reach statistical significance. A third trial is currently underway in the United States with Myotrophin, the results of which may be reported sometime this year. Therefore at this point in time, it is unclear as to whether IGF-I is effective in slowing disease progression in patients with ALS. There is evidence that IPLEX is different from the synthetic forms of IGF-I. The binding protein IGFBP-3, which is a component of IPLEX, modulates the activity of IGF-I. One of the roles of IGFBP-3 is to prolong the length of time that IGF-I circulates in the bloodstream. Incorporating IGFBP3 also blocks the hypoglycemic action (blood glucose lowering action) of IGF-I which allows higher doses of IGF-I to be administered. In order to be an effective treatment of ALS it is important for IGF-I to cross the blood brain barrier. It is possible that by having higher amounts of IGF-I circulating in the bloodstream for a longer period of time, greater amounts of IGF-I may penetrate into the brain. In addition, it could be possible that the IGFBP-3 contained in IPLEX helps to transport IGF-I directly into the brain. For these reasons it is important to study the effects of IPLEX as a treatment for ALS. Expanded Access Program in Italy The Agenzia Italiana del farmaco (AIFA) first contacted Insmed in the summer of 2003 about providing IPLEX to patients in Italy. AIFA stated that the Italian Court had examined the clinical documents of an adult patient believed to be suffering from ALS and had decided that he must be treated with IGF-I. We agreed to provide IPLEX at a price to cover our cost to the first patient in Italy in the summer of 2004. In the fall of 2006, we began receiving several new requests from physicians of patients in Italy diagnosed with ALS who received court orders stipulating IPLEX treatment. At that time we, with AIFA’s guidance, established a formal Expanded Access Program to provide IPLEX to physicians for their patients. As part of this program, physicians are required to collect and provide safety information as well as information pertaining to the progression or improvement in the functional manifestations of the disease prior to beginning treatment and every 3 months thereafter. The functional manifestations of the disease are being evaluated using an ALS Functional Rating Scale which is designed to evaluate speech, salivation, swallowing, handwriting, cutting foods and handling utensils, dressing and hygiene, turning in bed and adjusting bed cloths, walking, climbing stairs and respiratory function. The purpose for collecting this information is to help ensure the safety of patients and to gain an understanding as to whether or not IPLEX treatment provides benefit to these patients. There are approximately 30 patients who are currently enrolled in the EAP with additional patients being added periodically. These patients are located throughout Italy from the Calabria region in the south to the Lombardy region in the north and in Sicily and Sardinia as well. Most patients have been receiving 1 injection of 1 vial of IPLEX per day. For a 60 kg person this is equal to 0.5 mg/kg of IPLEX which contains approximately 0.10 mg/kg of rhIGF-I. Patients in the Myotrophin studies received 2 injections of 0.05 mg/kg of rhIGF-I a day for a total daily dose of 0.10 mg/kg. Therefore, to date, most of the patients in the EAP have received the same total daily amount of rhIGF-I as the patients in the Myotrophin studies. So far this dose has been well tolerated and we have not had any reports of serious side effects related to the treatment. We are in the process of having physicians increase the dose to 1 mg/kg and maintain the patients at this dose in order to evaluate the effectiveness of the drug. For most of these patients, the process for obtaining IPLEX begins with patients petitioning the Italian Court for treatment. Following a court decision stipulating IPLEX treatment, Insmed is contacted by the treating physician or the patient’s pharmacist. We in turn, provide instructions to the physician and/or pharmacist along with the relevant documentation for the physician and pharmacist to fill out. Once all of the required documents and import licenses are in place we ship IPLEX to the patient’s pharmacy. Insmed recognizes that ALS is a devastating disease and that there are patients throughout the world who are in need of an effective treatment. However, the Expanded Access Program is restricted exclusively to Italy through license agreements with companies who hold the patent rights for the manufacture and use of IGF-I products in the treatment of ALS. Insmed does not currently have the rights to manufacture or distribute IPLEX for the treatment of ALS outside of Italy. Therefore we are unable to provide IPLEX to physicians for the treatment of their patients anywhere else in the world.