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THGRF PROMISING TO BENEFIT COPD PATIENTS WITH MUSCLE WASTING.



Theratechnologies (TSX TSX Toronto Stock Exchange (TSE before April, 2002)
TSX Transfer from Stack Pointer to Index
TSX True Space Extension
: TH), Montreal, has announced preliminary results for a Phase II study testing ThGRF, its growth hormone-releasing factor growth hormone-releasing factor or growth hormone-releasing hormone
n. Abbr. GHRF, GH-RF
See somatoliberin.
 analogue, in patients suffering from chronic wasting, or muscle depletion, secondary to chronic obstructive pulmonary disease chronic obstructive pulmonary disease
n. Abbr. COPD
A chronic lung disease, such as asthma or emphysema, in which breathing becomes slowed or forced.
 (COPD COPD chronic obstructive pulmonary disease.

COPD
abbr.
chronic obstructive pulmonary disease


Chronic obstructive pulmonary disease (COPD) 
). Highlights included positive effects on body composition (increased muscle and decreased fat), a series of converging positive findings in functional measures, and a very good safety profile. Taken together, the company considers that the results suggest an improvement in clinical condition and provide a rationale for moving ThGRF into late-stage development in COPD wasting.

Dr. Annemie Schols is associate professor of Pulmonology pul·mo·nol·o·gy
n.
The branch of medicine that deals with diseases of the respiratory system.


pulmonology The study of the lungs and respiratory function
 at the Department of Respiratory Medicine at Maastricht University in the Netherlands. She is a leading authority on COPD wasting, an advisor to Theratechnologies, and an investigator in this study. "The results of this study are promising, because they demonstrate that ThGRF has the potential to bring clinical benefit in COPD patients with muscle wasting. The effects on body composition are impressive because the patients were not receiving any other rehabilitation therapy, such as exercise or nutritional intervention. Furthermore, the functional parameters that seem to respond to a short period of ThGRF treatment are those that you would expect to respond to anabolic anabolic

pertaining to or arising from anabolism.


anabolic steroid
steroids with a tissue-building effect. Testosterone is an example of a natural anabolic steroid with the, sometimes undesirable, effect of causing masculinization.
 treatment. What's also very interesting is that the clinical benefits appear to extend to patients who have progressed into severe wasting. This is a large body of patients who are in a very serious clinical condition without satisfactory treatment alternatives. It will be very exciting, if the next large-scale clinical trial is focused on this patient group, with a longer term treatment," Dr. Schols concluded.

According to Dr. Thierry Abribat, Theratechnologies' vice president and chief scientific officer, the study findings are significant in many ways. "The effect of growth hormone growth hormone or somatotropin (sōmăt'ətrō`pən), glycoprotein hormone released by the anterior pituitary gland that is necessary for normal skeletal growth in humans (see protein).  on body composition has been known for more than ten years but trials in adults have surfaced safety concerns and evidence of a corresponding improvement in muscle function has been inconsistent. As such, the results we are announcing today represent a significant advance in growth hormone therapeutics and a major turning point for our product, ThGRF. Not only do the results support proceeding with COPD wasting as an indication but these data are promising with respect to other indications associated with chronic wasting such as congestive heart failure congestive heart failure, inability of the heart to expel sufficient blood to keep pace with the metabolic demands of the body. In the healthy individual the heart can tolerate large increases of workload for a considerable length of time.  or chronic renal failure chronic renal failure Chronic kidney failure Nephrology A slow decline in renal function, which may be 2º to chronic HTN, DM, CHF, SLE, or sickle cell anemia and, if extreme, leads to ESRD, mandating kidney dialysis; an abrupt decline in renal function may be . This is also encouraging news for our two ongoing Phase II studies in hip fracture hip fracture Orthopedic surgery A femoral fracture which affects 1/6 white ♀–US during life Epidemiology 250,000/yr–US Specifics Proximal femur; 90+% femoral neck, intertrochanteric; 5-10% are subtrochanteric Risk factors Tall, thin ♀,  wasting and HIV-related lipodystrophy", Dr. Abribat noted.

Luc Vachon, vice president, Drug Development, at Theratechnologies, oversaw the study and is pleased with the outcome. "With this study, we have added valuable information to our already extensive knowledge of ThGRF. In terms of primary activity, we now have confirmed that our product builds lean body mass, or muscle, and reduces fat mass. We have also obtained evidence of a set of positive clinical outcomes, which make sense from a physiological perspective; and with well over 300 patients and healthy volunteers already exposed to the product, we have a very good safety profile. We have consulted with our advisors on the results of this study and on the unmet medical need that ThGRF could address in COPD wasting. Taking all of this into consideration, we believe that there is a strong case to be made for ThGRF as a potential treatment for COPD wasting and an opportunity to move forward to a later-stage of development in this indication," Dr. Vachon concluded.

Relevant findings

In the overall population, a three-month ThGRF treatment induced significant changes in body composition:

- A 50 % increase in IGF-1 levels at 1 mg (p less than 0.001 vs. placebo) and 92% increase at 2 mg (p less than 0.001 vs. placebo), as compared with a 6% decrease on placebo;

- A significant increase in muscle mass (lean body mass; LBM LBM Lean Body Mass (medical/health)
LBM Lumber and Building Materials
LBM Pounds Mass
LBM Lattice Boltzmann Model
LBM Laser Beam Machining
LBM Little Brown Mushroom (mycologist slang) 
), with a net average gain of 1.3 kg muscle mass in the 1 mg group (P less than 0.01 vs. placebo) and 0.9 kg in the 2 mg group (P less than 0.02 vs. placebo), as compared to an average loss of 0.1 kg in the placebo group.

- A significant loss in fat mass (FM), with a net average loss of 0.7 kg fat at 1 mg (p less than 0.01 vs. placebo) and 0.5 kg at 2 mg (p less than 0.05 vs. placebo), as compared to an average gain of 0.4 kg in the placebo group.

- There were no differences observed between the treatment groups in terms of safety assessments, and no sign of immunogenicity immunogenicity /im·mu·no·ge·nic·i·ty/ (-je-nis´it-e) the property enabling a substance to provoke an immune response, or the degree to which a substance possesses this property.  (antibody formation) was detected in any of the patients.

Interestingly, the effect of ThGRF on body composition was at least as strong in patients with the most severe wasting, which is a clinically defined group, based on their body mass index, who represented 23% of the total patient population:

- An average gain in LBM of 1.1 kg muscle mass in the 1 mg group (p less than 0.02 vs. placebo) and 1,8 kg in the 2 mg group (p less than 0.01 vs. placebo), as compared to an average loss of 0.1 kg in the placebo group.

- An average loss in FM of 1.1 kg fat in the 1 mg group (p less than 0.05 vs. placebo) and 0.9 kg in the 2 mg group (p less than 0.05 vs. placebo), as compared to a gain of 0.4 kg in the placebo group.

Additional assessments were conducted in order to investigate whether the expected changes in body composition translated into a functional improvement over the 3-month study period. From a preliminary evaluation of the data, including exploratory analyses, some reached statistical significance while some did not. Amongst these, the following converging findings suggest that ThGRF improved the clinical condition of these patients:

- A decrease in leg fatigue during exercise endurance test (Borg Scale Borg scale Chest medicine A system for scoring the perception of
dyspnea, consisting of a linear scale ranking the degree of difficulty in breathing, ranging from none–0 to maximum–10
) at 2 mg in the overall population (p less than 0.01; placebo NS, vs. baseline);

- A decrease in breathing discomfort during exercise endurance test (Borg Scale) at 2 mg in the overall population (p (equal sign) 0.01; placebo NS, vs. baseline);

- A trend for an increase in the physical function score of SF-36, a quality of life questionnaire, at 2 mg in the overall population (p (equal sign) 0.09; placebo NS; vs. baseline);

- An increase in muscle strength at the quadriceps level at 1 mg and a trend for an increase at 2 mg in patients with the most severe wasting (1 mg: p (equal sign) 0.05; 2 mg: p (equal sign) 0.11; placebo NS, vs. baseline);

- A trend for an increase in maximal pulmonary inspiratory in·spi·ra·to·ry
adj.
Of, relating to, or used for the drawing in of air.



inspiratory

pertaining to or used in the inspiration of air into the lungs.
 pressure (PImax) at 2 mg in patients with the most severe wasting (p (equal sign) 0.09; placebo NS; vs. baseline).

These parameters are highly relevant to anabolic treatment and the objectives of this study. This is true of quadriceps strength because in COPD wasting, muscle weakness affects the leg more than the arm. Similarly, PIMax is more dependent on respiratory muscle functionality than other pulmonary parameters and both the PIMax improvement and the increase in quadriceps strength would support the observed improvement in the Borg scales (leg and breathing discomfort). Finally, the SF-36 subscale that improved is related to muscle functionality.

The next steps for ThGRF

Theratechnologies has two additional Phase II studies underway. The first is measuring the efficacy of ThGRF in the recovery of wasting patients following hip fracture surgery with results expected in December 2003. The second is measuring the lipolytic lipolytic,
adj/n the ability to break up fat.
 effect of ThGRF in HIV-related lipodystrophy, a metabolic syndrome, with results expected in the first quarter of 2004.

Looking to the future, Luc Tanguay, president and CEO (1) (Chief Executive Officer) The highest individual in command of an organization. Typically the president of the company, the CEO reports to the Chairman of the Board.  of Theratechnologies said, "Today's results add to the already promising profile of ThGRF. Our strategy has been to capitalize on the product's unique safety profile by targeting indications above and beyond the existing US $1.7 billion market for growth hormone deficiency growth hormone deficiency Hypopituitarism Endocrinology A condition which affects 1:4000 children; ♂:♀, 3-4:1 Etiology 70% of GHD is idiopathic and attributed to a prenatal insult, possibly due to hypothalamic dysfunction, given that GHD children  (GHD GHD Growth Hormone Deficiency
GHD Good Humanitarian Donorship
GHD Good Hair Day
GHD Gutteridge Haskins and Davey
GHD Graduate Hall Director (university housing)
GHD Global Help Desk
GHD Growth Hormone Disorder
). We believe we now have the basis to pursue COPD wasting as an initial indication for ThGRF and our analysis indicates that this is potentially a very large market. We estimate that there are approximately three million patients with severe COPD wasting in North America, Europe and Japan.

"I want to acknowledge the hard work of our advisors, the investigators and everyone at Theratechnologies who contributed to this project and to congratulate them on the results announced today. We still have a lot to do but, with one potential indication in hand and the results of two ongoing Phase II studies to come, we are increasingly confident that ThGRF will be a very important drug in the years ahead," Tanguay concluded.

About the study

Conducted in 20 centers in Canada and Europe, this double-blind, randomized ran·dom·ize  
tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es
To make random in arrangement, especially in order to control the variables in an experiment.
, parallel group and placebo-controlled Phase II study was aimed at evaluating the efficacy and safety of two doses of ThGRF (1 mg and 2 mg), administered daily over a three-month period, on body composition, functional status, respiratory function and quality of life in 90 patients of 50 years of age and over.

The overall patient population was representative of a non-obese COPD population and included patients with various degrees (mild to severe) of COPD severity, the pulmonary component of the disease, as defined by the American Thoracic Society American Thoracic Society (ATS ), established in 1905, is an independently incorporated, international, educational and scientific society, serving its 18,000 members world-wide who are dedicated in respiratory and critical care medicine.  criteria, and various degrees of muscle depletion, or wasting, the peripheral component of the disease, as defined by Body Mass Index (BMI BMI body mass index.

BMI
abbr.
body mass index


Body mass index (BMI)
A measurement that has replaced weight as the preferred determinant of obesity.
) or Fat-Free Mass Index (FFMI FFMI Feri Fund Market Information (European fund research specialist) ).

About COPD wasting

COPD is a multi-component disease, implying two major components, the pulmonary and the periphery (muscle mass). The evolution of these two components is not parallel. Several prospective and retrospective studies have clearly demonstrated that involuntary weight loss or a loss in lean body mass are independent predictors of mortality, and are associated with diminished endurance exercise capacity, impaired quality of life and increase utilization of health care costs. In this regard, ThGRF is currently developed as the first compound for the treatment of muscle depletion, or wasting, associated with COPD.

About ThGRF

ThGRF is a stabilized analogue of the growth hormone-releasing factor (GRF GRF Graph (File Name Extension)
GRF General Revenue Fund (Canada)
GRF General Revenue Fund (United States)
GRF Growth hormone-Releasing Factor
GRF Global Relief Foundation
) that induces the production and secretion of growth hormone in a specific, physiological, controlled and pulsatile pulsatile /pul·sa·tile/ (pul´sah-til) characterized by a rhythmic pulsation.

pul·sa·tile
adj.
Undergoing pulsation.



pulsatile

characterized by a rhythmic pulsation.
 fashion. This property makes it a strong candidate as a potential treatment for many diseases related to aging and obesity, as these conditions are characterized by a significant reduction in growth hormone secretion.

The results studies conducted to date, involving over 400 healthy subjects and patients, have established a safety profile for ThGRF that differentiates it from growth-hormone-based products. In addition, its emerging pharmacological profile identifies two distinct mechanisms of action and two therapeutic fields, each with attractive market potential.

- Because of its positive effect on the secretion of an anabolic factor known as IGF-1, ThGRF may have a therapeutic effect on catabolic Catabolic
A metabolic process in which energy is released through the conversion of complex molecules into simpler ones.

Mentioned in: Anabolic Steroid Use


catabolic

see catabolism.
 states characterized by a reduction in the ability to synthesize proteins, as well as muscle wasting and cachexia cachexia /ca·chex·ia/ (kah-kek´se-ah) a profound and marked state of constitutional disorder; general ill health and malnutrition. , which often lead to loss of autonomy and death. The company has undertaken two efficacy studies in this field. The first concerns catabolic states related to chronic obstructive pulmonary disease (COPD) and is the subject of this press release; the second concerns catabolic states following hip fracture in elderly patients with results expected in December 2003.

- Because of its cholesterol-lowering effect and the direct lipolytic effect of growth hormone, ThGRF also has therapeutic potential in certain metabolic diseases. The company is currently conducting a Phase II study targeting lipodystrophy related to HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. . Positive results in this indication could enlarge the field of investigation for ThGRF to include the metabolic syndrome (Syndrome X). The results of this study are expected in the first quarter of 2004.

About Theratechnologies

Theratechnologies (TSX:TH) is a Canadian biotechnology company engaged in the discovery and development of therapeutic products in the field of endocrinology and metabolism. The company has and is developing a portfolio of peptides at various stages of development for the treatment of catabolic (loss of the body's synthesis and regeneration capacity) and metabolic disorders, as well as osteoporosis and type II diabetes Type II diabetes
Type II diabetes is the most common form of diabetes and usually appears in middle aged adults. It is often associated with obesity and may be delayed or controlled with diet and exercise.

Mentioned in: Diabetic Ketoacidosis
. In addition, Theratechnologies is expanding its peptide portfolio through proven, proprietary technologies. Its subsidiary, Celmed BioSciences, develops cell-based therapies for the treatment of hematological hematological, hematologic

pertaining to or emanating from blood cells.


hematological tests
total and differential white cell counts, hematocrit estimation, erythrocyte count.
, immune and neurodegenerative disorders.

For more information, visit http://www.theratech.com or call 514/336-4804, ext. 234.
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Publication:Worldwide Biotech
Date:Dec 1, 2003
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