Products
Fentanyl TAIFUN®
PRODUCT OVERVIEW:
AKELA Pharma is developing Fentanyl TAIFUN inhaler, a next generation treatment for breakthrough cancer pain. Based on AKELA’s proprietary multi-dose dry powder inhalation platform, Fentanyl TAIFUN promises cancer patients a significant advance in the management of breakthrough pain.
Fentanyl is a well studied opioid analgesic first approved as an intravenous agent in 1968 (USA). Since then, fentanyl has been incorporated into a number of different dosage forms for the treatment of both acute and chronic pain in the outpatient setting.
AKELA Pharma is developing fentanyl in its TAIFUN inhalation delivery platform. Inhalation is a very attractive alternative to intravenous administration when the objective is rapid onset of action and greater convenience. When compared with other dosage forms used for the treatment of breakthrough pain, the inhalation route offers greater convenience and a more rapid onset of pain relief.
MEDICAL NEED:
Breakthrough cancer pain has a rapid onset of action, often within seconds, and lasts for minutes to hours, with a median duration of about 30 to 60 minutes, before spontaneously subsiding. Breakthrough cancer pain is a significant problem for cancer patients despite taking optimal chronic pain medication. It is estimated that 800,000 cancer patients in the USA, and 700,000 patients in Europe, suffer from breakthrough cancer pain.
CLINICAL STATUS:
AKELA reported in March 2007 positive results from the open-label part of its Fentanyl TAIFUN® Phase IIb clinical trial. The results from 24 patients demonstrated successful dose titration resulting in effective control of breakthrough pain episodes. All 24 patients were successfully titrated to a dose of 400µg or less. From these first 24 patients, 9 patients titrated to 100µg, 10 patients titrated to 200µg and only 5 patients titrated to 400 µg. The patients experienced significant pain relief (defined as a decrease of at least 2 points on the Numerical Pain Scale, NPS) in 95% of the pain episodes treated. The estimate of the median time to significant pain relief was 7 minutes. Based on the interim adverse event data, Fentanyl TAIFUN® doses have been well tolerated and adverse events recorded were in accordance with previously disclosed Fentanyl TAIFUN® clinical trial data therefore suggesting high tolerability of Fentanyl TAIFUN® in opioid tolerant cancer patients.
Akela reported in September 2007 positive results from the double-blind part of its Fentanyl TAIFUN® Phase IIb clinical trial. The results demonstrated statistically significant differences compared to placebo in the measured primary and secondary efficacy variables resulting in faster and superior pain relief.
A total of 50 patients were randomized and started the extension part of the study. In the Intent-To-Treat (ITT) population, the median time to significant pain relief in the Fentanyl TAIFUN® group as measured by a decrease of at least 2 points on the numerical pain scale (NPS) was 5.2 minutes, which was statistically significantly faster when compared to placebo (P=0.007). The mean difference in sum of pain intensity difference (SPID) was also statistically significantly in favor of Fentanyl TAIFUN® for the whole 60 min pain episode (P=0.050). This was already seen in numerical pain scale scores up to 15 minutes (P=0.008) when compared to placebo.
Phase IIb for Fentanyl TAIFUN® was a multi-center, multinational clinical trial in cancer patients with severe persistent pain on maintenance opioid therapy. The first part of the trial was a single arm, open-label dose titration to evaluate the effective individual dose for significant pain relief with Fentanyl TAIFUN® in the treatment of breakthrough cancer pain. The second part included responders from the open-label part randomized to receive the titrated doses or placebo.
The excellent titration success and very fast onset of action obtained with Fentanyl TAIFUN® compares very favorably with data published from trials on transmucosal fentanyl preparations. In these trials, higher doses and a broader titration range have been required, and still the proportion of patients that were successfully titrated was lower, and onset of efficacy much slower. This apparent opioid sparing effect of Fentanyl TAIFUN®, with a narrow range of titration, is most likely due to the unique pharmacokinetic profile of the product, which combines an essentially immediate absorption of the drug with a prolonged and relatively steady concentration for the duration of a typical breakthrough pain attack.
PARTNERSHIP STATUS:
AKELA Pharma is seeking to partner the development and commercialization of Fentanyl TAIFUN for the North American market. AKELA currently has partnerships with Janssen Pharmaceutica NV for the European Union and with Teikoku Seiyaku and SK Pharma for selected Asian markets.
AKELA CGRP
PRODUCT OVERVIEW:
AKELA CGRP is a peptide, currently in Phase II development, for the treatment of allergic asthma. CGRP, calcitonin gene related peptide, is a natural peptide (37 amino-acids) produced in the lung in response to allergic stimuli. Unlike current asthma drugs, CGRP has been shown to possess a combination of broncho-dilatory, broncho-protective, and anti-inflammatory properties in several preclinical animal models of allergic asthma. From a therapeutic point of view, these properties of CGRP indicate a potential for CGRP to become the first hybrid drug offering anti-inflammatory and broncho-dilatory benefits.
MEDICAL NEED:
The initial CGRP target indication is the acute and prophylactic treatment of seasonal allergic asthma in children and adults.
MARKET OVERVIEW:
In the United States, the Centers for Disease Control and Prevention estimate that over 20 million people suffer from asthma with an alarming increase in the prevalence of asthma in the pediatric population. Asthma is a major cause of hospital emergency visits every year. According to the National Institute of Health, the direct healthcare costs associated with treating asthma in the United States reached an estimated $11.5 billion in 2003.
CLINICAL STATUS:
AKELA successfully completed (September 2005) a Phase I trial where CGRP was administered for the first time into the lungs of humans. The product was well tolerated and no serious adverse events were observed. LAB also reported positive results in October 2006 from its AKELA CGRP Phase IIa trial to investigate the protective efficacy of AKELA CGRP on metacholine induced bronchial hyper-responsiveness in adult patients with mild to moderate asthma, to compare this efficacy to salbutamol and placebo and to evaluate the safety and tolerability of AKELA CGRP in asthma patients. The trial enrolled a total of 12 patients. AKELA CGRP demonstrated statistically significant broncho-protective effects compared to placebo and a similar safety profile to placebo except for transient and mild headaches and flushing in some of the patients.
Akela is currently conducting a Phase IIb trial as a multi-centered, double-blind, placebo controlled, randomized cross-over study to evaluate the effects of inhaled CGRP on clinical and inflammatory parameters in adult patients with mild asthma following allergen challenge test. A total of 16 patients will be enrolled in two randomized one week treatment periods (either 5mg CGRP b.i.d. or placebo).
PARTNERSHIP STATUS:
AKELA Pharma is developing AKELA CGRP through Phase II validation studies with the intention of securing a partner to support further development and commercialization.
AKELA GHRH
PRODUCT OVERVIEW:
AKELA PHARMA’s GHRH (growth hormone releasing hormone) is in clinical Phase II development for the treatment of malnutrition in patients with Stage IV (pre-dialysis) chronic renal failure. LAB GHRH is a novel 29 amino-acid long peptide analogue that has demonstrated superior in-vivo potency in animals. LAB GHRH has exhibited increased resistance to proteolysis and a relatively high binding affinity to the human GHRH receptor in in-vitro studies, in comparison with human native GHRH (1-29)-NH2. AKELA GHRH acts in a more natural manner on the pituitary gland in the brain to stimulate release of growth hormone which further induces a cascade of actions including the release of IGF-1 which has a direct effect on lean muscle mass.
MEDICAL NEED:
Chronic renal failure is associated with a number of significant medical challenges including high blood pressure, anemia, weak bones, poor nutritional health and nerve damage. In sever cases, chronic renal failure leads to kidney failure and a requirement for dialysis. Malnutrition becomes a significant issue in more advanced cases and results in a loss of muscle mass that can further complicate renal disease and give rise to additional complications. The ability to prevent the loss of muscle mass while maintaining proper nutrition has the potential to improve day-to-day health as well as slow down the progression of chronic renal failure.
MARKET OVERVIEW:
An estimated 400,000 Americans have Stage IV (pre-dialysis) chronic renal failure and are in need of significant supportive care. In addition there are 300,000 with Stage V disease (dialysis) and 7.6 million patients with Stage III disease. It has been estimated that the total cost of kidney disease in the US was $35 Billion in 2003 (USRDS). There are no approved products for the management of malnutrition in chronic renal failure although growth hormone is used off-label for this indication.
CLINICAL STATUS:
AKELA Pharma plans to develop its GHRH by combining it to its proprietary inhalation formulation and delivery system. The product successfully completed clinical Phase I/II testing during Q3/2004 and the results showed a rapid and significant increase in the levels of growth hormone at all dosage levels and for all subjects. The study demonstrated the high safety profile of the compound at all doses administered, with no significant adverse events observed. AKELA has recently disclosed positive results of its Phase II trial to investigate the efficacy and safety of GHRH for the treatment of malnutrition in patients with late pre-dialysis chronic renal failure. Within 4 weeks of treatment, AKELA GHRH induced a highly significant stimulation of endogenous growth hormone (GH) secretion and a marked increase of circulating insulin-like growth factor (IGF-1) as compared to placebo in patients with chronic kidney disease. These endocrine effects were associated with a significant increase in Fat Free Mass (FFM), (the mean FFM value increased statistically significantly by 1.8 kg and in placebo decreased by 1.39 kg when compared to baseline), and a concomitant reduction in Fat Mass (FM), (the mean Fat Mass (kg) increased in placebo by 1.2 kg and decreased by 0.5 kg in the AKELA GHRH arm when compared to the pre-treatment level).
PARTNERSHIP STATUS:
AKELA Pharma is developing AKELA GHRH through Phase II validation studies with the intention of securing a partner to support further development and commercialization.
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