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About Akela Pharma Inc.
AKELA Pharma Inc. (TSX: AKL) is an integrated drug development company focused on developing therapies for the growing multi-billion dollar inhalation market. Its lead product, for the treatment of breakthrough cancer pain, is a fast-acting fentanyl formulation, delivered using the company’s approved TAIFUN® dry powder inhaler platform. Its pipeline also includes therapeutics for asthma, COPD, and growth hormone deficiencies. Akela’s common shares trade on the Toronto Stock Exchange ("TSX") under the symbol "AKL", on the Frankfurt Regulated Unofficial Market under the symbol "LD9.F" and on XETRA under the symbol "LD9.DE" with 30.9 million shares outstanding.
AKELA Pharma Inc. operations
In January 2004, Akela acquired 100% of the outstanding shares of Focus Inhalation Oy in Turku, a Finnish company formed as a spin-off of Schering AG and specializing in the development of inhalation delivery systems and therapeutics. By merging AKELA’s existing portfolio of proprietary products with the product portfolio, scientific excellence, regulatory approved inhaled drug delivery platform - TAIFUN® and substantial manufacturing infrastructure of Focus, AKELA Pharma emerged as one of the leading developers, formulation experts and manufacturers of inhaled therapeutics.
In January 2007, AKELA announced the closing of the acquisition of all of the outstanding membership interests of PharmaForm L.L.C., a privately held company headquartered in Austin, Texas. PharmaForm is a leading specialty contract service provider offering a portfolio of innovative technologies in drug product development, manufacturing and analytical testing. Through its diverse offerings, PharmaForm delivers drug product solutions that help clients reduce development costs and accelerate time-to-market. PharmaForm is currently expanding its drug product pipeline based upon its expertise in hot-melt extrusion and solids processing.
The acquisition of PharmaForm has brought AKELA significant new abilities directly related to our existing programs, as well as valuable platforms and products to broaden our pipeline. At the same time it has elevated AKELA’s profile in the world’s most important pharmaceutical and investment marketplace, the United States of America.
AKELA’s Development Portfolio
Fentanyl Taifun®
The lead development project within the AKELA development portfolio is an inhaled formulation of fentanyl for the treatment of breakthrough pain in cancer patients. Fentanyl is an opiate analgesic, a highly lipid soluble drug enabling its delivery via transdermal, transmucosal, and pulmonary routes.
AKELA is developing fentanyl by using its regulatory approved TAIFUN® inhalation delivery platform, as inhalation is proven to be the fastest and painless alternative to intravenous administration.
AKELA believes that the rapid onset of action and ease of use of Fentanyl TAIFUNÒ have clear advantages, compared to oral, transmucosal and injectable alternatives, and should significantly improve cancer pain therapy. AKELA has successfully completed (October 2005) an additional comparative Phase I trial with a peak plasma concentration of 935 pg/ml achieved within the first minute suggesting very rapid pain relief versus 371 pg/ml reached in one hour after the start of administration for the Actiq® 200µg lozenge. AKELA also reported positive results from a Phase IIa clinical trial in July 2006. The results supported clinical efficacy already at the lowest dose of 100 µg, and a trend of dose response relationship. The safety of Fentanyl TAIFUN® was similar to that of placebo, with the exception of an increase in mild to moderate somnolence. A total of 122 cancer patients on maintenance opioid therapy for persistent pain were enrolled in the Phase IIa trial. The analgesic efficacy in the responding patients was very rapid with Fentanyl TAIFUN®. In the Per Protocol analysis, time to significant pain relief was achieved on average in 7.8 to 11.6 minutes, depending on the dose.
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.
AKELA GHRH (Growth Hormone Releasing Hormone)
AKELA GHRH is a 29 amino-acid long peptide analogue, which has demonstrated, in-vivo, superior potency and GH secretion in animals, than the native GHRH (1-44)-NH2 and GHRH (1-29)-NH2. The originality and superiority of AKELA GHRH analogues are attributed to the fact that they exhibit increased resistance to proteolysis and have 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 was rationally designed by simple amino acid poly-substitutions with the aim to increase both its affinity to the pituitary GHRH receptor and its in-vivo half-life in plasma.
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).
3.5 TAIFUNÒ Inhalation Drug Delivery Platform
The TAIFUNÒ MDPI is an elegant and user-friendly multiple dose dry powder inhaler, designed to provide highly efficient delivery of the active drugs deep into the lung. It consists of a unique moisture-balancing drug reservoir, coupled with a patented volumetric dose metering system, ensuring consistent dosing throughout several months of product life.
The number and size of doses is adjustable to suit the drug concerned. An indicator shows the user the remaining amount of doses in the drug reservoir. Convenient administration is enabled by flow-rate independent breath actuation and breath actuated dosing, providing the patient with the confidence of effective delivery of the drug. This makes TAIFUNÒ suitable for a broad range of clinical conditions and different age groups, even if breathing is obstructed.
The TAIFUN® technology is covered by four (4) distinct patents, the longest extending up to at least 2017:
The dispensing unit (vortex chamber) of TAIFUN®
The dose metering unit of TAIFUN®
The desiccant system of TAIFUN®
The wet suspension method of powder formulation
Akela has the manufacturing capabilities necessary for high volume production requirements in large markets. |
