Biotech Values

[drbio45]

Osteologix OLGX Phase II Studies

The thing to realize is that the drug Protelos has a three hundred million dollar run rate per year in Europe.

link to 10k http://www.sec.gov/Archives/edgar/data/1278129/000136231009004693/c83320e10vk.htm

In November 2007, we completed a phase II double-blind, placebo-controlled randomized study of NB S101 in 289 post-menopausal women with low bone mineral density in order to assess the efficacy of our investigational drug. The trial participants were divided into five groups, with three of these groups receiving different doses of NB S101 (0.75 grams, 1.0 grams, and 2.0 grams), one group receiving placebo and one group receiving the approved 2.0 gram dose of Protelos® in sachet formulation (because Protelos is not in tablet formulation, the Protelos arm was not blinded to the treatment received). The patients in the trial were treated for 12 weeks and followed-up for four to eight weeks following completion of the treatment portion of the trial.
The primary endpoint in the study was the change in patients’ bone resorption, as measured by the biochemical marker CTX-1. We also captured data regarding the effect of NB S101 on bone formation, bone mineral density and a marker of cartilage degradation as well as the levels of strontium in patients’ serum and the side effects. The goal of our phase II study was to document the efficacy of NB S101 and to establish an effective and tolerable dose of NB S101 that will enable us or a pharmaceutical collaborator to initiate phase III clinical trials that would be designed to obtain approval of NB S101.
We met the primary endpoint for all three doses of NB S101 evaluated in the trial, showing a statistically significant reduction in CTX-1 as compared to placebo, in a dose dependent manner. The reductions in serum CTX-1 compared to placebo were 13.5 percent in the group receiving the lowest dose of NB S101 (0.75 grams), 15.5 percent in the group receiving the middle dose of NB S101 (1.0 gram), and 22.2 percent in the group receiving the highest dose of NB S101 (2.0 gram) (p<0.001 for all doses vs. placebo). These reductions in the marker for bone resorption were also numerically superior compared to the approved dose of Protelos (Protelos reduced the marker for bone resorption by 8.5 percent), although only the highest dose of NB S101 was statistically significant compared to Protelos. Data from the primary endpoint of the trial are shown in the chart below.


Primary endpoint — percent change in CTX-1 from baseline to week 12
Placebo Strontium Malonate Protelos®
0.75 g 1 g 2 g
N = 57 N = 57 N = 58 N = 56
Mean change from baseline relative to placebo, in percent N/A -13.48 -15.54 -22.17 -8.50
.001 .001 .001 .03
p-value
versus placebo <0.001


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In addition to meeting the primary endpoint, we also saw increases in BMD among the patients receiving NB S101 in comparison to patients on placebo, as shown in the chart of lumbar spine BMD below.


Lumbar spine — percent change in BMD from screening to week 12
Placebo Strontium Malonate Protelos®
0.75 mg 1 g 2 g
N = 56 N = 56 N = 51 N = 56 N = 55
Mean change from screening relative to placebo N/A 2.29 1.99 2.66 1.96
N/A .020 .049 .008 .048
p-value
versus placebo


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In our phase II clinical trial, NB S101 was well-tolerated and side effects were generally mild in all dose groups. There were no significant differences in the side effect profiles between the different treatment groups. It is our belief that the trial clearly demonstrates the beneficial effect of NB S101 on bone resorption and on patients’ bone mineral density after only a short treatment period and that more advanced clinical trials should be conducted to support the approval of NB S101.
Phase III Studies

We are designing our development plan for NB S101 for osteoporosis to comply with both U.S. and European guidelines. On February 17, 2009, we held a meeting with the FDA regarding the proposed development of NB S101. Based on feedback from the FDA meeting, we believe that the continued development of NB S101 will require an additional phase II trial and only one large, well-controlled phase III trial.
The FDA and EMEA require positive results from phase III studies before they will approve an NDA. In order to obtain approval for a new drug for the treatment of osteoporosis, current regulatory guidelines require placebo-controlled double-blind studies with fracture reduction as the primary endpoint. An adequate fracture-prevention trial represents a significant time and resource investment, as the treatment duration in the required clinical studies can be up to three years, although recent trials have been conducted with a two-year treatment duration and more recently an advisory group has recommended that these trials be reduced to 18 to 24 months in duration. These trials raise ethical questions concerning the use of placebo groups when approved drugs are available to treat osteoporosis, and both European and U.S. regulatory authorities are currently debating whether continued use of such trials can be recommended. If future guidelines prevent or limit the use of placebo control in such studies, we may plan to alternatively conduct a non-inferiority study against an established osteoporosis treatment or otherwise modify our plans based on any new guidelines established for approval of drugs to treat or prevent osteoporosis.
Based on the current FDA and EMEA guidelines and anticipated changes, we anticipate the primary objective of a phase III study will be to evaluate the ability of NB S101 to prevent incident vertebral fracture. We also anticipate that we would collect data on non-vertebral fractures, spine, hip and forearm BMD, and biochemical markers of bone and cartilage turnover. We estimate that the phase III study may enroll up to 3,000 osteoporotic women, comparing one dose of NB S101 to placebo over a two- to three-year treatment period, with a possible two-year extension. Based on continuing analysis of the phase II data and discussions with regulatory agencies, we are continuing statistical assessments before we finalize any phase III clinical trial design and determine the specific number of patients needed.
Our clinical development plans are based on the current profile of NB S101, our experience with preclinical and clinical testing of NB S101, our understanding of current FDA and EMEA guidelines, and our review of publicly available data on potentially competing products. We expect that continuing analysis of all data available on strontium, NB S101 specifically, and potentially competing drugs in development will increase our knowledge in the field, and may lead to our modifying our current development strategy. In addition, changes in market conditions or regulatory requirements may also require us to modify our development plans or perform additional pre-clinical trials.