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I agree, but most institutional investors are sitting on the side until the Libigel results kick in and FDA guidance. I have a good friend who is a regional manager for an investment firm and tweaked me to Biosante for the PDUFA play on Bio-t-gel. Nothing to do with Libigel. I got caught on the December drop and started to investigate. I have brought to his attention the CV data, the patents and the Vaccine award nomination. He was unaware of most of this, as his company has put Biosante on hold until June which is consistent with the conversations he has had with company management in December. Analyst have had similar conversations with Management that is why everyone has placed a hold on the company. I have yet to see an analyst recommend selling Biosante. They are in a hold pattern.
If June provides good news from FDA. The climb will start, the company will no doubt reiterate the good news events that have transpired since December that have been buried by the manipulation. To gain the effect it should of had.
There are too many things not happening behind the scenes that indicate something big is on the horizon.
Insiders are not buying at these prices most likely because they have insider information that has yet to be released by the company.
Info we know they could release:
- CV risk reduction patent application for both menopausal and HSDD has yet to be officially released
- The patent on commercial production of Libigel has yet to be officially released
- The GVAX vaccine being nominated as one of the top 5 vaccines and runner up for best licencing partnership with Aduro.
Info they most likely or should soon have:
- Extension trial results
- Minutes of FDA meeting re: HSDD and CV paths for Libigel.
- No doubt there is other info as well
Seems like the company is purposely trying to keep the share price down. The key question is why? A poster compared it to being played like very good poker hand.
Should be interesting to see if all this is to appease a suitable buyer or effect the R/S to ensure the next share offering would take them to a full service company that not only does R&D but manufactures, markets and distributes their products. Thereby keeping all the profits. If Libigel HSSD and CV pathways have been created for FDA approval, maybe this is the path in which Biosante is headed.
Voting Polls close May 29th @ 11:59 pm Eastern time.
It could, but it would be the MM selling to each other to drive the price down to accumulate more. That is why a number of orders are hard to fill. In the process they pick up additional shares by those fed up waiting for the stock to rebound. I expect the week leading up to the Jeffries Conference (June 4 - 7) to be information packed and price moving. It is a big conference and Biosante is presenting. I would be very surprised if a Libigel update and CV benefit are not announced just prior to the conference. They may still be waiting on safety data but should have had their FDA meeting.
Joshuri, the fact that they have ordered a filling machine for Libigel indicates that they have every intention of manufacturing the product. They already have a good R&D program with a number of products in the pipeline. If the FDA identifies a path moving forward on HSDD, Testosterone Restoration and the CV benefit, they may also be contemplating marketing the drug themselves rather then partner. The time awaiting PDUFA approval could be used to put a cracker jack marketing team together. This would eventually maximize their profits.
If this is the case you may not want to move on. In any event based on the FDA feedback any buyout offer would have to make sense.
Reality Check Time. The price drops have been based on less then 3% of stock on hand and that is if the MM haven't been trading back and forth to walk the price down. The last couple of weeks it has been around 1.5% of outstanding shares.
FDA meeting results will bring back volume and in likely hood the price.
There is a key word, many who are less familiar with the results of both the Bloom and Bliss trials are not aware of the importance of the word "and".
BioSante's corporate strategy always has included product development of high value medically-needed pharmaceutical products. In light of the top-line results from the two pivotal LibiGel Phase III efficacy trials, which indicated that LibiGel did not meet its co-primary or secondary endpoints, management continues to assess LibiGel's path forward and potential alternative strategies to utilize the continuing LibiGel Phase III cardiovascular events and breast cancer safety study.
Libigel is still being examined for HSDD, however should this fail they have enough data to submit an NDA to be used as the only proven safe low dose Testosterone Replacement Therapy for women (placebo can't do this). Since over 4 million off label scripts are written every year for male testosterone, what physician would prescribe male testosterone when a FDA approved product is available. Prescribe Libigel then they have reduced their liability.
The word AND (not or) indicates that they are referring to ability of Libigel to reduce the risk cardiovascular events by 71% for which Biosante has submitted patent applications.
Manipulation (plain and simple) is the reason BPAX is valued at less than .50. How else do you explain a series of good news releases which should drive the price of a stock upward but has done the opposite? What you are describing is companies that have one or two products and never bring a product to FDA approval.
You can't honestly think that his company is worth about cash on hand.
I agree about not putting all your eggs in one basket. But if I only had one egg I would put it in Biosante.
I agree Jeff has been a wealth of information as well. The key to this company is patience. They are playing on the FDA's time clock, and the FDA wants them to succeed almost as much as we do. They want that long term low dose testosterone safety data.
I posted earlier about the new PDUFA guidance which kick in 2013. I strongly believe the Benefit-Risk Assessment will benefit Libigel. The FDA has done quite a few things differently with Biosante and Libigel, I expect Libigel will be a good litmus test for the Benefit-Risk Assessment portion of the guidance.
Nutsy, I have to thank you, it was a post you made earlier this year about Biosante and Libigel being alive, that got me to research the company, clinical trials and patents. Prior to that I was playing the bounce.
Not likely, $2.25 works out to a market cap of approx $272 million. Google biotech buyouts or takeovers for the last year. Many companies are going between $1.5 and $2.5 Billion with less then half the pipeline and revenue potential of Biosante. If the FDA clears a path for Libigel HSDD and a path forward on the CV benefits look for a deal somewhere between $5 - $10 Billion possibly even more given the fact that Gilead paid $11 Billion for Pharmassett for their lead product for new treatment for Hepatitis (no guarantee of approval) but the leader in the race.
The share price, no where near reflects the value of this company.
FDA SPA exposed? Very good chance that Libigel will prove efficacy without another trial for the following reasons.
November 2, 2005 - Biosante releases
Updated FDA Guidance for Testosterone Therapy
Note: Dr. Shames stated that the FDA acknowledges testosterone’s efficacy in treating HSDD and the need for testosterone products to be approved for women affected by this condition.
June 16, 2008 Biosante releases the following
BioSante Pharmaceuticals Announces FDA Special Protocol Assessment (SPA) for Expanded Indication of LibiGel® in FSD
"In addition to being another major milestone for BioSante, receiving a second SPA for naturally menopausal women is a significant development for the entire FSD category," said Stephen M. Simes, BioSanteís president & CEO. "This action by the FDA once again confirms FDAís position that FSD and HSDD are true diagnosable conditions that women experience, with measurable endpoints that can be evaluated and which deserve therapeutic options. Importantly, the FDA now officially has opined on this position for both surgically and naturally menopausal women
October 20th, 2010
Bloom trial changes
Inclusion criteria
This study is a randomized, double-blind, placebo-controlled, multi-center study of the safety and efficacy of LibiGel 300mcg in the treatment of HSDD in surgically menopausal women taking a stable dose of estrogen therapy.
changed to
This study is a randomized, double-blind, placebo-controlled, multi-center study of the safety and efficacy of LibiGel 300mcg in the treatment of HSDD in surgically menopausal women.
Why would Biosante do this having such good results with estrogen use as a criteria in phase II?
ANSWER: Because it is covered in the efficacy portion of the Bliss Trial
Bliss Trial
Excerpt from Bliss trial
Study treatment and procedures
Treatment
Participants are randomized in a 1:1 ratio to receive either 1% testosterone gel 0.22 g/d (LibiGel) or an equivalent weight of identical placebo gel daily. Randomization is stratified by use of postmenopausal hormone therapy (none, estrogen, or estrogen + progestogen).
Study procedures
There are 9 clinical visits and 14 telephone contacts during the course of the study (Figure 1). Office visits will occur at screening and randomization and at 3, 6, and 12 months postrandomization and yearly thereafter. Telephone contacts will be completed at week 6, month 9, and at 3-month intervals unless a clinical visit is required. Subjects are instructed to contact sites if they believe that they have experienced a CV event or breast cancer. At each scheduled contact, participants are asked about adverse events and health care and hospitalizations; questioned about specific androgenic side effects, potential CV events, and breast cancer; and undergo other assessments of safety and tolerability as well as laboratory measures.
Efficacy will be evaluated at office visits and telephone contacts using the Subject Global Assessment and Perception of Benefit Questions.(As per Simon J, Braunstein G, Nachtigall L, et al. Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab. 2005;90:5226–5233) Participants who discontinue study drug will be encouraged to complete all study visits, examinations, and questionnaires and to report potential CV events and breast cancer.
I had seen a site say the 10th and Bloomberg say the week of the 14th. If it the 8th, check the Jazz release as well see if they mention anything about Elestrins sales. It could give us a hint as to whether milestone payments are foreseeable in the future.
RG- Thanks but no need, just ensuring people don't get duped into losing their shares to the MM's is enough of reward.
Mo-John, statistically with the inclusion criteria used in the Bliss trial the general population with the same criteria have an expected number or percentage of cardiovascular events. It is this expected ratio with which Libigel and the placebo would be measured against. To date placebo has been on par (100%) with the general population that have the same criteria, while Libigel patients only experienced 29% of the expected cardiovascular events.
Just to add that in many cases there is a level of risk in the development of CV drugs (as with any other drug). It is not often that you come across a drug with this much clinical trial data already collected as there is with Libigel. A number of big pharma are in trouble with expiring patents. We saw Gilead purchase Pharmasset for $11 b to be best position to be first to market the new treatment for Hep C (in phase III trial) Zero revenue to speak of.
What do you think the value of Libigel as a Testosterone Replacement Heart Disease Prevention drug (First to Market), HSSD drug (First to Market)and possibly future Alzhiemer's drug would be worth? In my honest opinion the return on investment will be faster, greater and longer lasting with Libigel, GVAX, Pill Plus, Elestrin and Bio-t-Gel in a company's pocket.
Forgot to mention the obvious that of course the patent applications would have been submitted with the un-blinded data.
In addition to HSDD, the FDA meetings no doubt will involve how to best move forward with the discovery that low dose Testosterone reduces the risk of cardiovascular events.
Going one step further early intervention trials may help identify Libigel as a drug all post menopausal women should use as means to prevent heart disease.
Menopause and Heart Disease
Mo-John, check out the Bliss trial link, Table 1 shows the Bliss trial inclusion criteria. They all needed 2 or more points on a CV risk sale. Then check out Table 5 for the risk factor breakdown.
Bliss Trial
I believe they are considered moderately at risk of a CV event. Interestingly when the trial was first proposed it was for a lower risk group where the patients only needed a score of 1 point or more but the trial inclusion criteria was changed to 2 or more points 2009-11-12
Trial update
They and or the FDA really wanted to test the safety of low dose testosterone.
I have attached the link to the patent related to post menopausal women. read line 82 downward. It should answer your question.
Patent
Oh and yes it is Truly Major!!!!
Hopefully the FDA adopts the balanced approach to Benefit-Risk Assessment as outlined in the Summary Report of the Workshop on
The Development of a Model for Benefit-Risk Assessment of Medicines Based on Multi-Criteria - Decision Analysis
Benefit-Risk Assessment
The report recommends assigning a value to the following criteria.
Benefit
For each pivotal trial:
• Efficacy (primary endpoint) versus comparator and its clinical relevance (20/20)
• Statistical significance of the efficacy results (18/20)
• Clinical relevance of the primary endpoints (19/20)
• Representativity of the studied population for the population targeted in the label (18/20)
• Evidence for the efficacy in relevant subgroups (14/20)
• Design, conduct and statistical adequacy of the trial (18/20)
• Confirmation of treatment effect by results of non-primary endpoints (16/20) Testosterone restoration to pre-menopausal levels
General benefit criteria:
• Confirmation of efficacy by results of relevant non-pivotal trials and extensions (16/20) Previous Trials
• Anticipated patient compliance (11/20)
• Clustering (consistency) of results of the pivotal trials
Risk
• Overall incidence of adverse effects (from clinical trials) (16/20) Libigel vs Placebo
• Overall incidence of serious adverse effects (from clinical trials) (20/20) Libigel vs Placebo
• Discontinuation rate due to adverse effects (from clinical trials) (15/20)
• Incidence, seriousness and duration of specific adverse effects (from clinical trials and postmarketing surveillance) (20/20) 16
• Interactions with other drugs and with food (18/20)
• Safety in subgroups (e.g., age, race, sex) (20/20)
• Potential for off-label use leading to safety hazards (12/20) Not for Libigel but for the existing practice.
• Potential for non-demonstrated additional risk due to limitations of clinical trials and/or short market exposure
• Potential for non-demonstrated additional risk due to safety issues observed in preclinical safety studies but not in humans
• Potential for non-demonstrated additional risk due to safety issues observed with other medicines of the same pharmacological class (the latter three criteria were previously clustered in the survey as ‘generalizability of the safety profile to the general population’ (18/20))
Biosante could use this document to support the Benefit-Risk Assessment. I have hi-lighted criteria that will help offset the placebo effect and should clearly demonstrate the value in approving Libigel.
New PDUFA Guidelines will help get Libigel approved in 2013.
The NDA approval process is presently guided by the following:
SECTION A: PDUFA REAUTHORIZATION PERFORMANCE GOALS AND PROCEDURES FISCAL YEARS 2008 THROUGH 2012
2012 Guidelines
The process under which Libigel will be assessed has changed a little most importantly look at line
X. ENHANCING BENEFIT-RISK ASSESSMENT IN REGULATORY DECISION MAKING
PDUFA REAUTHORIZATION PERFORMANCE GOALS AND PROCEDURES FISCAL YEARS 2013 THROUGH 2017
2013 Guidelines
I expect Biosante to rely on this section to help negate the placebo effect.
Top level efficacy Bloom trial results were similar with Libigel and the placebo. Both demonstrated a mean change of in satisfying sexual events of approximately 3.
Now the Bliss trial results is indicating that the placebo had the expected number of cardiovascular events (100%) while Libigel only had 29% of the expected CV events.
Now using a simplified formula such as the following
Benefit / Risk = Value to the patient
Placebo 3/100 = .030
Libigel 3/29 = .103
Therefore it can be argued from a benefit-risk perspective Libigel is 243% more valuable to the patient then placebo.
Alpha611, take a good look at both company pipelines.
Now look at their market caps. ACTC has a market cap of $162 M while Bpax has a market cap of $62 M.
ACTC has one drug approved for phase II trial the rest is in phase 1 or less.
BPAX has taken Elestrin and Bio-t-gel through FDA approval and are on the verge of an NDA submission for Libigel for one or more treatments. In addition their cancer portfolio consist of 17 phase 1 or 2 trials. The Pill Plus will also most likely be starting a phase III trial later this year.
Not hard to see which is the best value long term. Short term is always less predictable as you can see by the share price for Bpax over the last couple of months.
Malc Stone thanks for the invite. Forgive me for responding publicly but I only have a free account - No time to day trade to make it worth it for me. Advaxis wasn't on my radar but I did notice it had won the vaccine award which is good for Advaxis. When time permits I will look further into the company and may very well be back.
Catalyst-The following should keep Biosante busy
Planned :
Announcement of Trial Extention results could prove efficacy in persistence of use over placebo just as it did with Intrinsa
Announcement of regarding FDA meetings with information on NDA submission for Libigel in one or more of the following HSDD, Testosterone and Cardiovascular Risk reduction, pending top line safety results for Libigel
Announcement of a second GVAX pancreatic cancer trial
Announcement of another GVAX prostate cancer trial most like Phase II with Yervoy (BMS)
Announcement that a Phase III trial for The Pill Plus has commenced.
Q1 Results
Announcement of Bio-T-Gel launch date by Teva (may be in May 9 Q1 release) this will show the first date that Biosante will start to receive regular revenue.
Biosante Q1 (release May 10th ) - Did Biosante receive a payment for Bio-t-gel approval or is it strictly upon commercialization?
Jazz Q1 ( release May 8th ) looking for insight on Elestrin sales (could raise expectation that milestone payments will be reached at some point)
Not planned but expected:
In light of the recent articles surrounding patents and that Larger Pharmaceuticals are looking for companies to replace their lead products coming off patent. I expect the Wall Street Journal to publish the Patent Board Biotech results next week or the following - They are compiled quarterly and teh last compilation was Feb 2nd. Last time it was published Biosante was in the top 20 but led all companies in research intensity. I am not certain if patent applications are evaluated. If so expect bump with this year’s patent applications.
Partnering on Libigel NDA submission and CV Trial
Partnering on GVAX trials (i.e. BMS for GVAX Prostate)
Serious buyout offer for all or part of the company. (Note: it has to make sense for them to accept)
JAZZ will expand global network with acquisition of EUSA, since Elestrin is the lead drug in Jazz’s women’s health division, I expect a global (excluding Isreal Valeant owns this market) or European licencing deal for Elestrin which Jazz would be responsible for regulatory approval This too will create a regular revenue stream
There may be more catalyst that I am unaware of or forgot. But this will keep them busy for the next quarter.
Hi Double Die, I'll see what I can come up with.
Basically when Biosante merged with Cell Genesys had a market cap of
approx. $32 M with $35 M in cash. GVAX was down for the count as the Vital trials were stopped.
http://www.biocentury.com/companies/cell_genesys_inc
Since then Gvax is alive again and the there are presently 17 cancer phase 1 or 2 clinical trials.
Biosante has approx $50 m in cash
Elestrin is a marketed drug though only milestone payments are available off US sales. Biosante still has global rights to Elestrin
Bio-t-gel is approved and waiting to be marketed by Teva
Libigel is still alive and is likely to surpass the wildest expectation because of CV benefits that were discovered.
And the Pill Plus IS expected to start phase 3 trials this year.
By all accounts this is the closest you will ever get receiving shares in a company for free. What many don't realize is that you are really getting two companies for less then the price of one.
Informative post from the Yahoo Advaxis board which simplifies how GVAX is used. It leads me to believe that GVAX may end up being considered a first choice for partnership in order to stimulate the immune system to recognize cancer cells. The GM-CSF cytokine, that is engineered into cancer cells that are injected as a vaccine in the GVAX system, attracts immune cells to the site of vaccination. This "educates" the immune system to recognize the cancer cells.
Post from Advaxis board on GVAX & Aduro
I imagine in the week leading up to the Jefferies 2012 Global Healthcare Conference to take place June 4-7,2012 in New York.
Biosante is scheduled to present.
Interestingly last year this was the timeline leading up to the conference.
05/31/2011 BioSante Pharmaceuticals Completes Enrollment in LibiGel® Phase III Safety Study
06/06/2011 BioSante Pharmaceuticals Announces Lifting of Clinical Hold on GVAX Prostate Cancer Vaccine
06/07/2011 BioSante Pharmaceuticals, Inc. To Present at Jefferies Global Healthcare Conference
06/09/2011 Biosante presented at the conference
I don't know how long prior to May 31,2011 the last patient was enrolled, but it was announced on the 31st. For all we know the last patient may have already passed the 1 year mark (the minimum time within the safety trial for the last patient before FDA will entertain an NDA submission).
If they announce that they plan on making an FDA submission for Libigel and announce the CV benefit just prior to the conference, it could get a lot of attention. It is a very large global conference with many heavy hitters presenting.
Vivus presently has a market cap of $2.18 B with no revenue to speak of. If the results of the FDA meeting lead to a Libigel NDA submission in the fall along with the announcement of a path forward on the CV benefits of Libigel, Biosante could very well end up in a similar market cap area.
With companies like Pfizer looking to purchase companies in the $4 B range. Biosante could fit right in this price range. Then again with Biotech prices escalating such as Pharmasset selling for $11 billion on the back of their Hepatitis C treatment, also a company with no revenues to speak of, a Biosante sale could fetch an even higher price then $4 billion.
For investors the post FDA meeting announcements will give us a hint at how interesting (lucrative) the next year might be.
Important evidence proving that Libigel efficacy was less an issue for the FDA then safety.
Interesting quote from Dr. Daniel Shames, Director of The Division of Reproductive and Urologic Products of the U.S. Food and Drug Administration (FDA)
Dr. Shames reported the FDA is pursuing what he himself calls a policy of "feasibility" that is, a level of study that can be accomplished affordably and in a timely manner. Importantly Dr. Shames stated that he agrees that testosterone is effective for HSDD and that the FDA is "not arguing about efficacy" of testosterone. Efficacy and some safety data will be required pre-marketing. Dr. Shames further stated that the FDA is willing to look at additional safety data provided "post marketing." Dr. Shames indicated thathe realizes that it is not economically feasible to complete a full safety database of information before marketing. In addition, he indicated that the FDA will consider supportive epidemiological data and surrogate endpoint information.
AIS Report
Biosante Updated FDA Guidance for Testosterone Therapy
It almost appears like the Libigel was used as a guinea pig to validate the subjective endpoints testing methods, as used in the Bloom Trials. Most scientist would prefer making their clinical argument based on the objective measurable data (i.e, testosterone levels) which Biosante has a proven efficacy in restoring to pre-menopausal levels over placebo and no doubt will be used in a NDA submission.
The elimination of patients using estrogen (likely reducing efficacy) Why would Biosante agree to this answer "Dr Shames Statement" and helping FDA by isolating the effects testosterone by itself.Libigel is the FDA's opportunity to get so many answers to low dose usage. Obviously Biosante will use subset data, persistence of use data from the trial extensions to reduce the weighting of external information.
I am more confident than ever that an NDA submission for Libigel for HSDD will be submitted once the safety data has been analyzed, probably in the fall. This may be accompanied by an Phase IIIb trial for enhanced efficacy allowing for estrogen to be used alongside Libigel(I am not sure this will be required) In any event the trial should be completed along with the results most likely not delaying the PDUFA date. Upon approval a phase IV trial will commence post marketing to enhance the safety profile data for the FDA.
Next how does Biosante proceed with the unexpected discovery that Libigel reduces the risk of cardiovascular events by 71%. I believe that this is where the meat of the discussions with the FDA will focus on. Don't be surprise, that once the CV subset data has been analyzed, Biosante announces a series of Phase III or IIIb trials isolating the most promising groups. within the exclusion criteria.
Postmenopausal women at least 50 y of age with a clinical diagnosis of HSDD (might have enough data to add for labeling to the NDA submission in the fall)
The following may require additional phase 3 or 3 b trials.
a. Age, 60 to <70 y (1 point) or =70 y
b. Diabetes mellitus
c. Peripheral vascular disease with ankle-brachial index <0.6
d. Documented CV disease (myocardial infarction, stroke, hospitalization for unstable angina/acute coronary syndrome, revascularization of the coronary or peripheral circulations)
e. Present smoker of at least 10 cigarettes per day (or the equivalent)
f. Hypertension—defined as seated systolic blood pressure =150 mm Hg and/or diastolic blood pressure =95 mm Hg and/or taking antihypertensive medications (for treatment of hypertension)
g. Dyslipidemia—low-density lipoprotein >160 mg/dL and/or high-density liproprotein <45 mg/dL with triglycerides >250 mg/dL and/or taking prescribed lipid-lowering medication
The presentation this week on Pill Plus should make for interesting conversation. Interesting to see if the presenter will hint as to when a Phase III trial would start.
The World Congress on Building Consensus in Gynecology, Infertility and Perinatology (BCGIP): Barcelona, Spain
May 4th 17:15-17:45 presentation
The pill plus: Should this formulation replace the current use one?
H. Coelingh Bennink, The Netherlands
World Congress
For those voting no to R/S in the proxy please read the following. Biosante may need it to get an extension,
What happens if a company does not regain compliance with the minimum bid price requirement during the compliance period?
If a company is unable to resolve its bid price deficiency during the applicable compliance period, NASDAQ Staff will issue a delisting letter. At that time, the company may request a hearing before a Listing Qualifications Panel, which will stay the delisting.
The company will have the opportunity to present its plan to regain compliance to the Panel. This plan of compliance should include implementation of a reverse stock split in the near term. In appropriate cases, and so long as a company commits to implementation of a reverse split within 180 days of the delisting notification, Panels may also consider other factors, such as the company's fundamental financial strengths and weaknesses, the overall market, the company's historical bid price, and impending disclosures, corporate actions and strategic business plans that the company believes may impact its bid price.
FAQ
Good question!
To give you an idea how undervalued Biosante is Amgen is buying Kia Pharmaceuticals for $315 million for one drug in phase II trials and one pre-clinical. Take a look at their pipeline. Biosante would need a pps of $2.60 to have a market cap of the same value.
Offer
Kai Pipeline
Biosante to present at Jefferies 2012 Global Healthcare Conference
June 4-7, New York city.
Presenting Companies
The dates are consistent with when larger institutions were advised they would find out about how (or if) Libigel would go forward. This no doubt is one of the reasons larger institutions have not been overly active with this stock. This conference could change all that.
Vote on R/S will be behind them, opening the door for FDA meeting info on Libigel, this could include any or all of the following:
Subset analysis
Extension study
CV benefit announcement,
Maybe even the announcement of the intention of an NDA submission and a partner.
Should make for an interesting week.
Libigels extension study analysis should be completed or very close to completion by now.
Hopefully Libigel will produce similar persistence of treatment effects as Intrinsa
Excerprt from Intrinsa (Testosterone Transdermal System) -
NDA 21-769
4.9 PERSISTENCE OF TREATMENT EFFECT
The persistence of treatment effects was assessed during a 13-week double blind follow-up period (Weeks 53-65) of Studies 2001133 and 2001134. All subjects who completed both the 24 week double blind placebo-controlled phase and the subsequent 28 week open label TTS phase of the two phase 3 trials were offered the opportunity to participate in a study to evaluate persistence of treatment effect. Subjects who agreed to participate were asked a set of questions about their response to treatment during the previous 28-week open label period. The subset of subjects who
responded positively to specific questions, including having experienced an increase in desire for sexual activity and an increase in satisfying sexual activity compared with before entering the study, were randomized in a 1:1 ratio to receive placebo or TTS in a double-blind manner for 13 weeks. Sex therapists conducted follow-up telephone interviews with these subjects between Weeks 63 and 65 to assess persistence of treatment effect. Of the 205 subjects enrolled, 199 (97%) completed interviews.
The primary endpoint in this study was the sex therapists’ assessment of a “noticeable decrease” in desire for sexual activity during the 13 week treatment period. A higher percentage of women in the placebo group compared with TTS [62.7% vs. 43.3%] reported a “noticeable decrease” in desire for sexual activity during the 13 week study. In addition, a higher percentage of women in the placebo group compared to the TTS group [47.1% vs. 25.8%] reported experiencing a decrease in the frequency of SSEs.
FDA Intrinsa Medical Review
Upon reviewing the medical review and remembering a number of Nutsyprofessor, Jeffqdh and friends postings on Yahoo, I have to come to the same conclusion that Nusty has been saying about the FDA setting up the Bloom trials to play down efficacy to deter recreational use. Intrinsa patients were relatively healthy when compared to Libigel's patients. Biosante has some very smart people in the room and they have been going the extra mile for the FDA on this matter, more than would normally be required for drug approval. I can't see them not a creating a path to assist in countering the placebo effect (they help create) and getting the long term low dose testosterone safety data they obviously want.
Thanks Nutsy, this explains the protocol changes I noticed in the Libigel trials. Originally Estrogen was used then later it was an exclusion criteria. It would also explain why the phase II efficacy was so high in comparison to phase III. Another trial with estrogen would probably give similar results to phase II which were dramatic.
While they are at it, phase IIIb trials should be in the works to explore the CV benefits.
Elestrin may generate royalties yet. Since Jazz merged with Azur pharma with offices in Ireland and has an agreement to Acquire EUSA Pharma with offices in London. Jazz's global network will expand considerably. Combined with the fact that the growth in demand for Elestrin in the US has turned Elestrin into Jazz's lead women's health product. The next logical step to benefit both Jazz and Biosante is a licencing agreement to Jazz for Elestrin for the UK and the EU. With Jazz being responsible for the UK and EU approval process. With Elestrin being approved by the FDA and Isreal the approval process should be simplified.
JAZZ & EUSA
You will note that I stated potentially become secondary or primary prevention treatment. The fact is they have 5 years of safety data and very good spring board to launch further trials involving CV risk reduction.
Aspirin, for its blood thinning capabilities is viewed as both a primary and secondary prevention treatment. Why not testosterone restoration? Especially if the connection between low testosterone and CV disease is established.
Read the Bliss trial and you can see that the FDA clearly wants to get more information on the benefits of testosterone. They have added a 5 year commitment post approval to continue to testing for safety.
What the board all realizes is that if this discovery can be proven before the FDA through additional trails, it would be huge.
I am not as certain as you are on the negative effects of Libigel
Firstly Libigel has never been submitted the FDA. It is still in phase 3 trials.
Please educate me. This is the Bliss Trial for Libigel inclusion criteria:
1. Postmenopausal women at least 50 y of age with a clinical diagnosis of HSDD (DSM-IV)
2. CV disease risk score if =2(adapted from Barett-Connor et al7) using the following point scale:
a. Age, 60 to <70 y (1 point) or =70 y (2 points)
b. Diabetes mellitus (2 points)
c. Peripheral vascular disease with ankle-brachial index <0.6 (2 points)
d. Documented CV disease (myocardial infarction, stroke, hospitalization for unstable angina/acute coronary syndrome, revascularization of the coronary or peripheral circulations) (2 points)
e. Present smoker of at least 10 cigarettes per day (or the equivalent) (1 point)
f. Hypertension—defined as seated systolic blood pressure =150 mm Hg and/or diastolic blood pressure =95 mm Hg and/or taking antihypertensive medications (for treatment of hypertension)—(1 point)
g. Dyslipidemia—low-density lipoprotein >160 mg/dL and/or high-density liproprotein <45 mg/dL with triglycerides >250 mg/dL and/or taking prescribed lipid-lowering medication (1 point)
Now my understanding of the patent applications is that the above at risk group demonstrated a 71% reduction in risk of cardiovascular events. I was of the understanding that (rightly or wrongly) that this was a relatively new concept, hence the surprise and subsequent patent application.
Bliss trial
Methods for decreasing cardiovascular risk in postmenopausal women patent
Whether this is achieved by restoring testosterone to pre-menopausal, or if there is an underlying reason, I am not an expert. Is it the low dose combination with the method of delivery?
Thanks for nay further clarity. Because connecting the lead me to my assumptions. Am I a missing dots?