hey tuck
I've pasted the last conference call, where the CEO goes into very deep detail as to how they came up with the assumptions for their trials.
These concerns about the power of the trial appear to be the favorite chorus of the analysts. But as usual, it is the vacuous "things may not happen as they did before" caution, which isn't very informative imo... in fact, i thought that was the definition of biotech :-)
Anyways, steiner goes into detail regarding their trial (with references!). Having briefly followed this company, I can't say I fault them much for how they appear to have designed the trial as their thought process appears rational and reasonable (imo). Certainly they could have designed a mega-trial with twice the enrollment, but then the analysts would be squawking about how they'll need to raise cash before the trial results, or that if they're looking for a physiological phenomenon that is infrequent, is it clinically important enough to generate significant revenue, etc.. etc...
I think we're all familiar with the drill!
CORPORATE PARTICIPANTS
McDavid Stilwell
GTx, Inc. - Director - Corporate Communications & Financial Analysis
Mitchell Steiner
GTx, Inc. - CEO, Vice-Chairman
Marc Hanover
GTx, Inc. - President, COO
CONFERENCE CALL PARTICIPANTS
Eric Schmidt
Cowen & Company - Analyst
Joel Sendek
Lazard Capital Markets - Analyst
Meg Malloy
Goldman Sachs - Analyst
Aaron Reames
A.G. Edwards - Analyst
Gene Mack
HSBC Securities - Analyst
Chris McGordy
Rodman & Renshaw - Analyst
Howard Liang
Leerink Swann - Analyst
PRESENTATION
Operator
Good day, ladies and gentlemen, and welcome to the First Quarter GTx Incorporated Earnings Conference Call. My name is Francis, and I will be your operator for today.
(OPERATOR INSTRUCTIONS)
I would now like to turn the call over to McDavid Stilwell, the Director of Corporate Communications. Please proceed.
McDavid Stilwell - GTx, Inc. - Director - Corporate Communications & Financial Analysis
Thank you, and good morning. On behalf of GTx, I'd like to welcome you to our first quarter 2007 conference call. We released our results earlier this morning through the newswires.
If you do not have a copy of the release and want one, you will find it on our Web site at gtxinc.com. We will have a replay of this call available on our Web site until May 18, 2007.
With me today are Dr. Mitchell Steiner, Vice Chairman and Chief Executive Officer; Marc Hanover, President and Chief Operating Officer; Dr. Ronald Morton, Jr., Vice President and Chief Medical Officer; Dr. Gary Barnette, Vice President of Clinical Research and Development Strategy; and Mark Mosteller, Chief Financial Officer.
Following this introduction, Dr. Steiner will highlight first quarter 2007 clinical and corporate developments. Next, Mr. Hanover will briefly detail our financial performance. Dr. Steiner will then make closing remarks and open the call for questions.
Before we begin, I will remind you that information discussed on this call may include forward-looking statements, and such statements are subject to the risks and uncertainties we discuss in detail in our reports filed with the Securities and Exchange Commission, including in our Annual Report filed on Form 10-K, March 9, 2007.
We expressly disclaim any obligation to release publicly any updates to forward-looking statements made during this call.
Now, I'll turn the call over to Dr. Steiner.
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Thank you, McDavid. Good morning, and thank you for joining us on our first quarter 2007 earnings call. GTx continues to make good progress in the clinical development of Acapodene and Ostarine, and to move towards our commercialization goals.
In late January, an independent Data Safety Monitoring Board reviewed the safety data from the Phase III ADT and Phase III PIN clinical trials. After reviewing the unblinded safety records of more than 2900 patients, the DSMB recommended that GTx continue both clinical trials as planned.
This is reassuring but not surprising since the active ingredient in Acapodene, toremifene citrate, had been on the market since the mid 1990s for the treatment of advanced breast cancer, and the worldwide safety data base has more than 355,000 patient years of use on record.
In February at the 2007 ASCO Prostrate Cancer Symposium, presentations on the interim analysis from the Phase III ADT clinical trial, which show that Acapodene increased bone mineral density and lowered cholesterol, was selected by ASCO for a special press conference.
This pre-review recognition at ASCO Prostrate Cancer Symposium, along with the recent attention of the scientific literature and lay press about the heightened risk for fractures and cardiovascular disease in patients on ADT, underscored the growing recognition and the great medical need for treatment for multiple serious side effects of ADT.
The commercial prospects of an oral drug like Acapodene 80 milligrams that could potentially treat multiple side effect of ADT, not just osteoporosis couldn't be brighter.
We are approaching the completion of the Phase III ADT clinical trial with the last patient coming off the trial at the end of November.
GTx will work efficiently to lock down the data base and prepare top-line results as expeditiously as possible, to release to the public. As the date approaches, we will have more clarity over the timelines for the release of data.
We remain very confident with the design and status of the Phase III ADT clinical trial.
The primary endpoint of the Phase III ADT clinical trial is the reduction in the proportion of subjects with a morphometric vertebral fracture in men with advanced prostate cancer on androgen deprivation therapy in a Acopodene-treated compared to placebo group.
The protocol assumes that the rate of morphometric vertebral fractures over the two-year length of the study will be 16% in the placebo group, and with a 40% reduction in the Acapodene treated group.
Under the SPA, the study statistics were designed to have an 80% power and an alpha of 0.05 with a sample size of 1,200 randomized patients.
This intended sample size takes into account, a dropout rate of at least 25%. The number of patients that were actually randomized was 1,389. This is 189 more patients than we planned.
If the study assumptions are indeed correct, that is, if the morphometric vertebral fracture rate is 8% per year or 16% over the two-year study in the placebo group and if there is at least a 40% reduction of morphometric vertebral fractures in the Acapodene treated ADT patients, the actual p value would be 0.003.
This means that the trial is in fact overpowered as originally designed as we only need to hit a p value of less than 0.05 to achieve our primary endpoint.
The reason for this is that while we were designing the trial, we asked ourselves, "What if the assumptions about the actual morphometric vertebral fractures are too high? How low could the actual morphometric vertebral fracture rates be in the placebo group and still hit a p value of less than 0.05?"
Our statistical analysis shows that with a 40% reduction, the morphometric vertebral fracture rate could be as low as 3.35% per year, which would be a 6.7% over the two-year period in the placebo group and still achieve our primary endpoint with a p value of less than 0.05.
Now let's take a step back and I'll share with you how we came up with a 16% morphometric vertebral fracture rate over two years with 8% per year in the placebo group.
We went back to the data available in postmenopausal women in which morphometric vertebral fracture rates are well established and extrapolated from these data to get morphometric vertebral fracture rate in ADT men.
In postmenopausal women, there is a one-to-one ratio between morphometric vertebral fractures and non-traumatic, non-vertebral fractures. In ADT patients, (inaudible) in 2003 reported the non-traumatic, non-vertebral fracture rate is 8% per year.
Therefore, if you assume the ratio of non-traumatic, non-vertebral fractures to morphometric vertebral fractures is one-to-one, similar to postmenopausal females, the expected morphometric vertebral fracture rate in men on ADT will be 8% per year or 16% over the two-year study.
Although this was an educated guess at that time with the best data available at that time, we do now have contemporary clinical studies to support these assumptions, which I will share with you in a few moments.
Our next challenge was to do our best to enrich the study with patients who would have the highest risk for morphometric vertebral fractures.
As a consequence, we set up a very stringent inclusion-exclusion criteria for the Phase III ADT clinical trial. Subjects were only included if they had significant bone loss as evidenced by a T-Score for men of minus 1.6 or they were greater than 70 years of age.
It was worth it to us to do this at the front-end rather than take all comers on ADT. In fact, the baseline characteristics of our low patients suggest that we have truly selected out a high-risk population on ADT.
Let me share with you some of our observations about the baseline data.
First, although low bone mineral density is clearly a risk factor for fractures, there are special considerations that must be accounted for in our patient population. T-scores are used to describe the relative loss of bone, but there appear to be major differences between men and postmenopausal women and between young and older men.
For example, postmenopausal women are considered to be osteoporotic and high-risk for fractures if their T-score is less than minus 2.5 at any measure scalable site.
However, according to [Murrow et al] in 2007 and [Falkner et al] in 2002, BMD underestimates the true fracture risk in men.
In men over 50 years of age T-scores of minus 1.8 to minus 2.3, better defines osteoporosis and the risk of osteoporotic fractures.
Moreover, in older men, [Taxel et al] in 1998 reported that it is the BMD of the femoral neck that most closely associates with overall osteoporotic fracture risk in all sites.
In the Phase III ADT clinical trial, the mean T-score baseline in the femoral neck was on average, minus 1.5 for all subjects, which is quite low, considering the majority of subjects enrolled were over the age of 70 and did not need to meet the T-score criteria to enter the study.
Therefore, at the anatomical site that is most closely associated with osteoporotic fracture risk, the patients included in the Phase III ADT clinical trial had clear loss of bone at baseline, and with ADT will have accelerated bone loss and be at even a higher risk for fractures.
Now the reason that we allowed patients older than 70 years of age to enter the trial regardless of BMD status, is because as reported by [Regs et al] in 1986, age itself is a risk factor for the development of vertebral fractures in men.
[Inten et al] in 2002 made the observation that lumbar BMD alone is not as predictive for vertebral fractures and the explanation was that 70% to 90% of people over the age of 75 have osteoarthritis.
[Arthur et al] in 1999, Schneider in 2006 state, that owing to the extra calcifications associated with osteoarthritis, bone mineral density can be possibly elevated and may not be representative of the true risk of osteoporotic fractures.
However, it should be noted that when compared to baseline, improvement in BMP of the lumbar spine are predictive of vertebral fracture benefit. This is not only true for postmenopausal women, which has been well established, it also holds true for men.
It is clearly a clinically meaningful reduction in vertebral fractures in men who have a BMD lumbar spine improvement as was shown in the Actinal fracture study in glucocorticoid induced osteoporosis and also in the male osteoporosis bisphosphonate clinical trial as reported by [Orwel et al] in 2000.
These clinical trials actually measured fractures, not just BMD in men. Thus, for our ADT study, the average age is 76. The advanced age of these patients in our study is an independent risk factor for the development of osteoporotic fractures.
Due to the incidents of osteoarthritis at this advanced age, bone mineral density at baseline in the lumbar spine alone may not be as an accurate predictor of osteoporotic vertebral fractures.
Moreover, the increase in BMD in the lumbar spine as low as at every scalable site that was measured in our Phase III interim analysis, provides confidence that we should have a fracture benefit in the lumbar spine.
Now there are two other factors that affect the risk of fracture and were considered in the trial design. There are the presence of a prevalent morphometric vertebral fracture and the duration of androgen deprivation therapy.
A previous vertebral fracture also called a prevalent vertebral fracture, is an independent risk factor of a future fracture.
In postmenopausal fracture studies, as we put in the Avista for scribing information, the annual morphometric vertebral rate in patients with a prevalent morphometric vertebral fracture at baseline is 6.7%, while in patients without a fracture at baseline, the annual rate of morphometric vertebral fracture is approximately 1.4%.
This represents a three-fold increase in fracture risk. [Owenphine et al] in 2006 reported about the same increase in vertebral fractures observed in men with a prevalent vertebral fracture with osteoporosis.
The baseline data from the Phase III ADT clinical trial revealed that 18.7% of men enrolled, had a prevalent vertebral fracture. This is important since this may affect the relative reduction in vertebral fracture rate.
Extrapolating against in the postmenopausal osteoporosis studies using a SARM, as reported in the Avista prescribing information, the percent reduction of vertebral fractures during the course of the trial was lower in patients with a prevalent vertebral fracture who had a 30% reduction compared to patients without a prevalent fracture who had a 55% reduction.
Based on these data, enrolling patients with a prevalent fracture, would significantly increase the overall fracture rate of the study, but the drug effect would likely be diminished.
We believe that we have a nicely balanced study since only 18.7% of the patients have a prevalent vertebral fracture, and 81.3% did not have a prevalent vertebral fracture baseline.
If similar reductions in fracture rates are seen in our Phase III ADT study compared to the Avista study in women using these various weighted averages, we would expect an overall percent reduction of greater than 40%.
The second consideration is time on androgen deprivation therapy, which is an independent risk factor for fractures.
In a study by [Smith et al] in 2004, the fracture risk was assessed for seven years and 3,807 patients with non-metastatic prostrate cancer who initiated ADT, and 7,774 patients with non-metastatic prostrate cancer who did not receive ADT.
Patients that have been on therapy for greater than three years had a significantly higher risk of fractures compared to patients of ADT for less than one year.
That p value was less than 0.01. The average time on ADT in our protocol at baseline was 3.17 years, and accordingly, these patients would be at a significantly higher risk for the development of an osteoporotic vertebral fracture.
All of these considerations taken together, the baseline data from our Phase III ADT clinical trial, and average age of 76, ADT duration of 3.17 years, femur BMD T-score of minus 1.5 and a prevalent fracture rate of 18.7%, supports a patient population that is sicker and more at risk to develop a vertebral fracture.
Now let's turn back to our trial assumptions. Our trial had the statistical power with a 40% reduction to have an actual placebo vertebral rate of 3.35% per year or 6.7% over two years and still be able to hit a p value less than 0.05.
Please keep these fraction numbers in mind and I will discuss why we're confident in our trial especially in light of the new vertebral fracture data in men with osteoporosis and in men with ADT that are now available, but were not at the time we designed the trial.
Let's review these studies. First, in male osteoporosis fracture studies, [Orwell et al] in 2000 reported the vertebral fracture rate over a two-year period in approximately 120 men with an average age of 63 was 7.1% or 3.55% per year.
Similarly, [Ring et al] in 2004 reported a vertebral fracture rate of 24.2% over three years or approximately 8% per year in 67 men with an average age of 53 years.
The following overall comments could be made about these studies. The patients in both of these male osteoporosis trials are very different from the patients in the Phase III ADT clinical trial.
These men are younger by an average age of up to 23 years, these men do not have prostrate cancer, these men are not on androgen deprivation therapy.
The range of vertebral fracture rates in men with osteoporosis varies widely between studies, and these cases ranging from 3.55% per year to 8% per year.
If we use these actual vertebral fracture rates for male osteoporosis patients in the statistical plan in our Phase III ADT clinical trial, that is, an annualized vertebral fracture rate of 3.55% in the placebo group with at least a 40% reduction in fractures, we would still hit with a p value less than 0.05 even though these men were younger and not on ADT.
Now let's turn to the data that is now available, to better understand the morphometric vertebral fracture rates in men on androgen deprivation therapy.
Today there have been two prospective trials conducted in men on ADT in which the annualized morphometric vertebral fracture rate may be gleamed.
[Smith et al] reported in 2003 that in a placebo controlled study of 106 men on ADT were non-metastatic prostrate cancer with an average age of 70, that eight radiographic vertebral fractures were diagnosed over a 12-month period, which is 7.5% per year.
Interestingly, five of these fractures occurred in men with baseline T-scores that were greater than minus 1.
In a Phase III, Zometa clinical trial of 643 men with hormone refractory prostrate cancer on ADT who had a median age of 72 years of age, of which 208 were in the placebo group, [Sayeed et al] in 2002 reported that 8% of the placebo group experienced a vertebral fracture over a 15-month period.
There were 23 vertebral fractures reported over 15 months in two arms and only three or 13% of these fractures were symptomatic.
Another way to predict the morphometric vertebral fracture rate in an ADT placebo group is to extrapolate the asymptomatic morphometric vertebral fracture rate from the symptomatic vertebral fracture rate in men on ADT.
Smith in 2005 reported that in a claims-based vertebral fractures occurred in ADT patients at a rate of 0.98% per year. This is claims based, which means that vertebral fractures were most likely symptomatic.
In the FDA clinical reviews of Zometa for the indication of treatment of skeletal related events in men with advanced prostrate cancer on ADT, there were 23 vertebral fractures reported over 15 months. 13% of these vertebral fractures were symptomatic.
If you consider the 0.98% per year in symptomatic fractures in the claims based study represents 13% of the total vertebral fractures, then the actual rate of asymptomatic morphometric vertebral fractures would be 7.5% per year.
The overall conclusions of these studies are as follows. The subjects included in these ADT clinical trials are similar to those enrolled in our Phase III ADT clinical trial. These subjects had prostrate cancer, these subjects are on androgen deprivation therapy and the mean ages in these studies are comparable to that seen in our ongoing study.
Of significant importance is that the baseline BMD T-score was not an inclusion-exclusion criteria for these studies. Vertebral fractures occurred in patients regardless of baseline T-score.
These studies that enrolled similar populations to that use in our trial, the morphometric vertebral fracture rate was 6.4% to 7.5% for 12 months and if the placebo fracture rates in this range are also observed in our Phase III ADT clinical trial, we would certainly reach statistical significance with a p value less than 0.01, well below our hurdle of 0.05.
In conclusion, we have confidence that the ongoing Phase III ADT clinical trial is sufficiently powered to detect at least a 40% reduction in morphometric vertebral fractures and hit a p value of less than 0.05 even if the actual morphometric vertebral rate is as low as 3.35% per year or 6.7% for the entire study in the placebo arm.
Contemporary studies in ADT patients of similar age regardless of entry BMD T-score, have vertebral fracture rates of 6.4% to 7.5% per year or 12.8% to 15% for the two-year study.
Our interim analysis of the Phase III ADT study showed highly statistically significant increases in BMD in all three scales of sites measured and based on the weighted average of reduction in vertebral fractures in postmenopausal women taking Avista, we would expect a fracture reduction of greater than 40%.
Today, we have been tracking the blinded aggregate vertebral fractures in our Phase III ADT trial and although we cannot share the actual rates, I'm confident that we're on track.
Those who would like to have the actual references of these studies discussed in my comments, they may be obtained through a link on the front page of our Web site at www.gtxinc.com.
As for the Phase III PIN study, in February the Journal of Clinical Cancer Research published the identification of an ABCA5 protein as a molecular marker specific to high grade PIN, as well as the clinical study results of the urine based test and its sensitivity and specificity to identify men with high grade PIN.
This test is being developed by MacroArray Technologies, one of the five diagnostic companies collaborating with GTx in the development of a noninvasive blood or urine test for high grade PIN.
MacroArray's Chief Scientific Officer, Dr. Mark Stearns, confirmed at the recent GTx Analysts Day event, that his company continues to make progress in the late stage development of this test and expects the test to be commercially available in 2009.
GTx is on schedule to conduct an interim efficacy analysis in the pivotal Phase III PIN clinical trial, evaluating Acapodene 20 milligrams for the prevention of prostrate cancer in men with high grade PIN in the fourth quarter of 2007 to the first quarter of 2008.
If that interim efficacy analysis achieves the pre-specified level of statistical significance, GTx will proceed with filing a new drug application.
Now, I would like to turn the call over to Marc Hanover.
Marc Hanover - GTx, Inc. - President, COO
Thank you, Mitch. Good morning. The details of our financial results for the first quarter 2007 are included in this morning's press release and are available on our Web site. I will focus on the highlights.
The net loss for the quarter was $8.1 million or $0.23 per share compared with a net loss of $9.9 million or $0.32 per share in the first quarter of 2006.
Revenue for the first quarter of 2007 was $1.7 million compared to $1.2 million for the same period last year. Revenues for 2007 included $192,000 of net sales of Fareston and $1.5 million of collaboration income from our European partner, Ipsen.
Research and development expenses were $8 million and general and administrative expenses were $3.1 million for the three months ended March 31, 2007 compared with $8.4 million and $3 million for the first quarter of 2006.
At March 31, GTx had $111.4 million in cash and cash equivalents. GTx has no debt and no warrants.
As we have mentioned before, our current cash is sufficient to fund operations through the first quarter of 2009. This timeline does not take into account the possibility of receiving milestone payments from our partner Ipsen, or the potential for an Asian partnership for Acapodene.
If we receive cash from one or the other of these opportunities, we may be able to extend our cash runway further into 2009.
I will now turn the call back to Mitch.
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Thank you, Marc. At the GTx Analysts Day meeting held last month in New York, we reiterated our confidence in the expected timelines for the two Acapodene clinical trials, we laid out plans for the clinical development of ostarine and we introduced two new clinical programs from GTx's own pipeline.
Within the next few weeks, we will initiate a placebo-controlled, double-blind, randomized Phase IIb Ostarine clinical trial for the treatment of cancer cachexia in a 150 patients with non-small cell lung cancer.
Patients will be randomized to receive placebo, ostarine 1 milligram, or ostarine 3 milligrams. The primary endpoint of the trial would be totally in body mass at four months and secondary endpoints will be totally in body mass at six months as well as measurements of muscle performance at four and six months.
The second indication selected for clinical development of ostarine, is chronic kidney disease muscle wasting. Last weekend we held a Key Opinion Leaders meeting in Houston, Texas, to get input on the clinical trial design.
By the end of 2007, GTx plans to initiate a Phase IIb Ostarine clinical trial for muscle wasting associated with chronic kidney disease.
GTx selected these indications based on the favorable safety and efficacy data we observed in the Ostarine Phase II proof of concept trial we conducted last year and after having a series of meetings with the FDA, to better understand the regulatory pathway to these and other indications that are under consideration.
Both cancer cachexia and chronic kidney disease muscle wasting, represent large premium market and unmet medical needs with no current FDA approved treatment.
It is important to know that in the Phase II Ostarine clinical trial of 120 patients treated three months for sarcopenia, ostarine improved insulin resistance.
The data revealed that Ostarine 3 milligrams reduced fasting blood glucose by 11% and insulin by 17.6% and lowered insulin resistance by 26.8%.
The effect was even more pronounced in a subset of patients who were pre-diabetic for whom blood glucose declined by 17.4%, insulin by 29.4%, and insulin resistance by 41.3%.
The ostarine data in pre-diabetic patients compares favorable to the published studies of FDA approved drugs like rosiglitazone, glipizide, and metformin.
The planned Phase IIb Ostarine clinical trial in chronic kidney disease muscle wasting, provides an ideal opportunity to evaluate the potential of ostarine to reduce insulin resistance in diabetes.
As nephrologists report that approximately half of all Stage III and Stage IV chronic kidney disease patients are diabetic and a majority of the remaining patients are pre-diabetic.
Also, at the GTx Analyst Day Meeting, we introduced two new clinical programs. First, GTx 838. This is another SARM that we're going to develop for sarcopenia. The patent life of GTx 838 extends until 2027. We expect to file an IND by December 2007.
The second new clinical program that we introduced is GTx 878, an ER beta Agonist for BPH. In pre-clinical models, GTx 878 is anti-prostatic and anti-inflammatory. This could indeed represent a new class of BPH drugs. We expect to file an IND for GTx 878 in the first half of 2008.
GTx has positioned itself to potentially file a new drug application annually for the next four years -- Acapodene 80 milligrams with the side effects of ADT in 2008, Acapodene 20 milligrams for the prevention of prostrate cancer in 2009, ostarine for cancer cachexia in 2010, and ostarine for chronic kidney disease muscle wasting in 2011.
Again, to remind you, if you'd like to have the references that I mentioned in my earlier comments in regard to our Phase III ADT clinical trial, they will be available through a link on the front page of our Web site at www.gtxinc.com.
Operator, we are now ready to take questions.
QUESTION AND ANSWER
Operator
(OPERATOR INSTRUCTIONS). And your first question comes from the line of Eric Schmidt with Cowen. Please proceed.
Eric Schmidt - Cowen & Company - Analyst
Good morning. I appreciate the information on the ADT trial power, Mitch. Just in terms of the timing of that study, I know you said the last patient was -- it was going to be in late 2007. It would seem, therefore, and I don't want to put words in your mouth, but it seems pretty unrealistic.
I would think you need several months to clean the database and get the results into a format before unblinding, so, we're really looking at Q1 of '08 now?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Be realistic. We've been tracking the trial and the last patient will come out in November of this year. Even under the most aggressive circumstances, it appears unlikely that we're going to be able to do the queries and lock down the data base and have everything before Christmas.
So, I think it is realistic to expect that the trial is on track, the trial is on time, but from a trial management statistical standpoint, we just have to wait until they've cleaned the data up and have it ready for us for topline.
Eric Schmidt - Cowen & Company - Analyst
Okay. And then do you have a better sense on the PIN study as well as to whether that would be either in Q4 or Q1?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Yes, that's been kind of a fun study because it's event based. And so it's somewhat like a race in some ways, but I will tell you that we're well on track with that.
I really cannot give you any clarity on whether that will be a Q4 event this year or a Q1 event next year. All I can tell you is it's definitely in the window.
So, it's not like I'm going to say, "Well I don't know, it looks like we're going to be tracking it till next year late." No, it's definitely in the window. I just can't tell you whether it can be sooner or later except that it's tracking very nicely.
Eric Schmidt - Cowen & Company - Analyst
Okay, that's helpful, thank you.
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Thank you, Eric.
Operator
And your next question comes from the line of Joel Sendek with Lazard Capital Market. Please proceed.
Joel Sendek - Lazard Capital Markets - Analyst
Hi, good morning.
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Good morning.
Joel Sendek - Lazard Capital Markets - Analyst
Until Marc got on, I thought I dialed into a PhD defense by mistake.
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Well, yes. That's what I told, Marc. I told, Marc.
Joel Sendek - Lazard Capital Markets - Analyst
But, I do have a question that having to do with one of the things you said at the end, Mitch.
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Okay.
Joel Sendek - Lazard Capital Markets - Analyst
Which is, do you have in your own possession, the blinded fracture data or is that in the hands of the DSMD and they're just telling you that they're analyzing it on -- either doing a futility analysis?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
I'll answer it two ways. First of all, the Data Safety Monitoring Board's job is only to look at safety. There are no rules in place for them to address efficacy. So, the data remains blinded.
However, we do follow as I said in my comments, we do follow the aggregate -- blinded aggregated vertebral fracture rate and that's why I made the comment that I feel comfortable we're on track.
Joel Sendek - Lazard Capital Markets - Analyst
Okay. And then with regard to your comfort level, I'm wondering, obviously, you're not going to give us those numbers, but is your comfort level due to the fact that -- is that comfort level based on the overpowering that resulted from that there were 189 extra patients, or would you be at the similar comfort level if you weren't overpowered in that regard?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
So, the question is -- the question is, do we feel confident because based on the trial design at the original number of patients being 1,200, since we've put 189 more patients, oh boy, that got us over the hump?
No, even without the 189 patients, the comfort level was clearly there and the trial as designed, once you get the data, would have had a p value of 0.003 and that has to do with the valuable patients more than patients randomized.
So, that's why we felt confident -- comfortable.
Joel Sendek - Lazard Capital Markets - Analyst
Okay. And with regard to the fracture rate, is that real time as of today or is there any kind of a lag on your ability to see that data?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
There is a lag and so my comments is a real time comment, it's only based on the right sought recently, but there is a lag from the time [Cenarc], which is our Central Radiology Group reads it and the time that we put back to it.
I will tell you that here we confident and recognize now that the majority of our patients haven't even made it past 24 months yet. So, if this is exponential rate, then that's even more encouraging.
Joel Sendek - Lazard Capital Markets - Analyst
Okay, thank you.
Operator
Your next question comes from the line of Meg Malloy with Goldman Sachs. Please proceed.
Meg Malloy - Goldman Sachs - Analyst
Thanks. Actually my question has been answered, but a quick one for Marc. Are you reiterating your '07 guidance?
Marc Hanover - GTx, Inc. - President, COO
Yes, Meg, I am. We are reiterating 45 to 55 and I know the run rate is a little bit light this quarter in terms of it being around the $8 million number.
But, given the fact that the two Phase IIbs are going to kick in the second half of the year, I expect those expenses to increase and again I feel comfortable it will be within the range.
Meg Malloy - Goldman Sachs - Analyst
Thank you.
Operator
Your next question comes from the line of Aaron Reames with A.G. Edwards. Please proceed.
Aaron Reames - A.G. Edwards - Analyst
Thank you for taking the question and I appreciate the comprehensive review earlier. I was wondering if you could just touch on something a little bit -- in a little bit more detail in regard to the changes in bone mineral density over time between men and women.
It's my understanding that bone's vascular calcification in men appears as bone mineral density in the lumbar region, so you actually have patients that look healthier, when in fact it's because of this aberration of vascular calcification.
So, I was wondering if you could put into context when we see a T-value of negative 0.55 in men, how that kind of compares to equivalent rates in women et cetera?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Yes, first of all thanks for the question, Aaron. First of all, postmenopausal women in general are younger than the men in our study and so both patient populations develop osteoarthritis with time.
But the postmenopausal women in general tend to be younger than, for example, 76-year old men on ADT.
With that said, rather than focus on the baseline BMD, more important is to look at the change because all things, equal your osteoarthritis is kind of stable, what's going to be different is going to be the additional bone mineral density that you gain with the treatment of your drug.
So, improvements in BMD have been shown over and over in both male and female population to render a fracture benefit and that's true from glucocorticoid induced osteoporosis study and now the more recent male osteoporosis study.
So, when you look at a BMD score of minus 0.55 in the lumbar spine, you're looking only at the tail of the elephant because typically when osteoporosis T-scores are given, it's not given necessarily precise, what they do is they take the worst number and that's what the signs of the patient.
So, if the femoral neck or the femur is what's considered most closely related to a fracture of risk because of the fact of the osteoarthritis in the spine and all the extra calcification, then you would expect again to see the worst number get better, and we did see that. If you go back and look at our baseline data, all three scale for sites got better.
The next thing is, you got to look at the data. The data clue shows that in ADT men, regardless of their initial BMD, again this is just confirming what we just said, just another piece of the elephant, that these patients regardless of how they are randomized with their BMD in the spine, that these patients did go on to have the requisite number of fractures and so now with BMD improvement and having the right number of fractures, it's tracking the way we expect it to track.
Aaron Reames - A.G. Edwards - Analyst
Thank you.
Operator
Your next question comes from the line of Gene Mack with HSBC Securities. Please proceed.
Gene Mack - HSBC Securities - Analyst
Thanks for taking the question, Mitch. I've got to admit I probably got a bit of comprehensive review. I'm just wondering and I apologize if you've already sort of gone over this, but you've talked a great deal about making sure you had patients with sufficient risk of a fracture.
I'm just wondering at what point, what gets you comfortable that you have gotten -- haven't crossed the line where sort of the horses are out of the barn and patients are the ones where you can actually have a delta or different that would get you confident that you can correct the fractures that you seem to have a great deal of confidence (inaudible)?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Gene, thank you for the question. The question basically is almost like, what are you seeing and do you have enough of events to achieve the delta that you're trying to achieve at the end of the study? Is that correct?
Gene Mack - HSBC Securities - Analyst
Yes, more or less. I mean, I guess it was really a -- what I am trying to get to is, are these patients at such a high risk of fracture that intervention at this stage isn't going to help?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Oh. I see. No, no, no. I hear your question. The question is almost like the prevalent fracture studies that you see in postmenopausal women that they are "so bad off that any drug intervention is not going to help them."
And the truth in the matter is, it's not that it doesn't help them, it's just that the placebo group has so many fractures that there's noise in the system. So, when you've got inevitable fractures independent of treatment occurring in both arms that cancels out your delta.
So, in our situation, they want backup, but still even then, the fracture reduction was about 30% to 33%, in postmenopausal women that were heavily weighted, in a sense they all had prevalent fractures.
In our situation, we have about 80% of the patients who have never had a fracture before, and sure there's accelerated bone loss, and the way that we capture the same information they capture in postmenopausal women, is the fact that in postmenopausal women those studies are done over three years and we're doing it over two years.
And so, the goal would be to be able to expect a delta to be more like the fracture naive patients than in the prevalent fracture patients. That makes sense.
Gene Mack - HSBC Securities - Analyst
Got it, thanks a lot, Mitch.
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Thank you, Gene.
Operator
Your next question comes from the line of [Chris McGordy] with Rodman and Renshaw. Please proceed.
Chris McGordy - Rodman & Renshaw - Analyst
Yes, hi. Thanks for taking my question. I was wondering how or where do you feel the urology community is with regard to ADT related osteoporosis?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
So, the question -- thank you for the question. The question is, how much education is GTx going to have to do for the urology community?
And let me just give you a couple of facts. First of all, approximately 90% to 95% of the patients that have hormone sensitive advanced prostrate cancer are currently in the hands of urologists.
So, it's a very important question that you've asked because you're basically saying that these are not necessarily made up of oncology patients that have already had hormone refractory prostrate, they are on chemotherapy, they've got other things going on.
So, about 90% to 95% of these patients will be in the hands of the urologists, and it's critical that the urologists should be aware of bone loss in these patients.
Interestingly, over the last five years there's been an exponential increase in the awareness of this condition by urologists.
We have recently conducted a survey in over 133 community based urologists and actually got the results of that survey back in March of this year, which is basically five to six weeks ago.
I was very impressed to see that approximately 80% of these community based urologists felt the bone loss was an issue and that 50% were trying to find some way to treat these patients even though they didn't have anything really to treat them. I would not have expected such a high number.
The other important piece of information is there are about 4,000 urologists out there that would be sort of in the top-tier of urologists that would be seeing patients with prostrate cancer.
Just by virtue of our clinical trials which is 150 [side], and you start taking into account the principle investigators or the sub-PI, we touch about 1,500 of them and we've touched 1,500 of them now for about four years.
So, the effort to go out there and to continue to educate this group is going to be required that I'm feeling pretty good with the growing awareness in the urology community is where it should be for a bone loss and certainly for other side effects of androgen deprivation therapy.
Chris McGordy - Rodman & Renshaw - Analyst
Yes, thank you. I just have one follow-on. The thing is, I want to ask about ostarine. What would happen if ostarine is taken by healthy, young adults?
Obviously, it would have the same effects you see in the patient population, the trial you had, and how can you detect ostarine in the blood? Is there a blood test or a urine test?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
This has to do with abused potential?
Chris McGordy - Rodman & Renshaw - Analyst
Yes.
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
So the question is, how is GTx going to monitor abused potential for a drug that has the potential to be abused such as an anabolic non-steroidal agent that is potent like ostarine?
And the answer is, we've already been contacted by numerous Olympic committees across the world and typically, they've already asked for a way to measure ostarine in athletes and we're going to provide them the assays to do that.
Approximately, 22 muscle sites have already started talking about ostarine, so there's clearly a buzz amongst the athletes around this compound. But, it can be measured certainly by us providing them with the assays.
But, also it is an anabolic agent, so if you go back and look at our data, any anabolic agent will lower something called sex hormone binding globulins and even if the agency can't measure the actual doping agent, they can tell if the individual is on a doping agent, just by mere fact of measuring something like sex hormone binding globulin which will allow them to see whether somebody is abusing an anabolic agent.
Chris McGordy - Rodman & Renshaw - Analyst
Okay, thank you. That was helpful.
Operator
(OPERATOR INSTRUCTIONS). Your next question comes from the line of Howard Liang with Leerink Swann. Please proceed.
Howard Liang - Leerink Swann - Analyst
Thanks very much. I just thank you for taking the time to review all the data. I have a question regarding the assumptions. You talked about the sensitivity of the powering to the event rate.
Can you talk about the sensitivity to the effect side, for example, the reduction in the fracture rate is now 40% rather than for example 30%. How would that affect the outcome?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Howard, thank you for the question. As you know, the SPA says that you need to hit 40% and so if you're less than 40% and you hit, then that's going to become the discussion with the FDA, that's beyond the scope of the SPA.
With that said, a lot of that's going to depend on what the actual event rate turns out to be and we do have a lot of room to go down and then it becomes an issue of what is clinically relevant and a way you can discuss with the FDA that they would say, "Okay fine, if you hit a 30% reduction" is that going to be considered clinically significant in a patient population that has a 39-month reduction in median light if they develop a fracture, say, if you can get a discussion with the FDA.
Another interesting tidbit is what happens if the reduction is greater than we think. So for example, for every 5% increase in effect side we will see halfing, or you can half your p values.
Another way of saying it is that if you had 0.05 and you have a 5% increase in your delta over 40%, then you'll be down in the p value 0.025 and so on and so on. So, the effect size that you're eluding to, Howard, is really going to be generating the p value.
We're comfortable that based on the statistics that the trial was designed that we've got a lot of room. If we're below 40%, that's a different kind of discussion irrelevant of the p value.
Howard Liang - Leerink Swann - Analyst
Okay. Switching gears to SARM, can you talk about the clinical news flow of ostarine data? Will present at any clinical meeting?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Yes. And we've been invited, in fact most recently we were at the Society of Andrology invited a meeting and also the Society of Endocrinology, so all the major endocrine meetings have come out and invited GTx's scientists to come present our data.
So, at every major endocrine meeting coming up, GTx will provide the full set of data in a scientific peer review form.
But, just to let you know, we've got tremendous excitement by the endocrine and the andrology groups. And you can't have any meeting now without somebody asking for a slide from GTx to include in their presentation.
So, I think we're going to see a lot of data over the next six to eight months in these major meetings.
Howard Liang - Leerink Swann - Analyst
Okay, great. And just on the submission of ostarine regulatory front, what's your understanding of how big the safety database needs to be before you can send it?
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Yes. So, just to put it in perspective, as you know, when we did our Phase I, 96 patients, single-sending dose and we did our Phase I multiple sending dose study with approximately 72 patients.
We then came back into the United States and filed an IND. The IND for cancer cachexia was filed with the Oncology division. They have come back even as the green lights were on track.
No regulatory obstacles to start our cancer cachexia trial next month. But, your safety database is going to be dependent on the indication that you go after. We will follow ICH guidelines. I will tell you that the numbers of patients and the time that we're planning to treat patients would fit the ICH guidelines.
But if we go into sarcopenia and some of those others, then that's going to have to be a discussion with the FDA that maybe over and beyond ICH guidelines.
Having said that, the safety profile that we've seen with ostarine so far appears to be extremely favorable and so consequently we think that that will be a low hurdle, but I can't really say until we have those actual discussions with the FDA.
Howard Liang - Leerink Swann - Analyst
Okay, thanks very much.
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Thank you, Howard.
Operator
And there are no further questions at this time. I would now like to return the call over to Dr. Steiner for closing remarks.
Mitchell Steiner - GTx, Inc. - CEO, Vice-Chairman
Thank you, operator. We would like to thank you all for your interest in GTx and we look forward to providing with updates on our future progress. Thank you again for joining us today on our call.
Operator
Thank you for your participation in today's conference. This concludes the presentation. You may now disconnect and have a good day. |
