Discussion in 'Men's Economics' started by Michael Scally MD, Aug 13, 2011.
You called this a very long time ago!
FDA Presses Pause on Novel testosterone Product
The FDA has cancelled an advisory committee, originally scheduled for Tuesday, that would have discussed a new drug application for a novel testosterone product.
Phase III results for enclomiphene citrate (Androxal), an oral estrogen receptor modulator, were reported last Thursday – http://www.medpagetoday.com/Endocrinology/GeneralEndocrinology/54380 - just before the FDA announced on its website that "outside, expert advice is no longer needed" for the expected advisory committee. The agency did not elaborate and did not respond to a request for clarification. http://www.fda.gov/AdvisoryCommittees/Calendar/ucm459227.htm
But in a conference call with shareholders, Joseph Podolski, president and CEO of Repros Therapeutics, which is developing the drug, said that the FDA had told the company of concerns that the method used for measuring testosterone levels hadn't been properly validated. http://www.reprosrx.com/investors_events.php
Podolski said the firm did use a properly certified lab running the Siemens Centaur Immunoassay system, which is "very well validated." http://www.healthcare.siemens.com/immunoassay/systems/advia-centaur-cp-immunoassay-sys
He added that the concerns over the method verification "might have been a hook for the FDA to try to put off this meeting, because there's a much bigger question here." The bigger questions are two-fold, according to the FDA's briefing document that Podolski said he viewed: Who should be treated with the product, and what should the clinical benefits be?
"I really think this was an opportunity for the FDA, and I don't blame them, to back away from the circus," he said, adding that he wished, however, that the FDA would have brought the issue up sooner.
He noted that the uses for testosterone have changed dramatically; traditionally it was used to treat hypogonadism only, but other drug companies have been aggressive in attempting to get it prescribed for men with low testosterone due to aging. Podolski said that he's convinced, from the research done thus far, that clinical benefits of testosterone products don't include increased libido. http://www.medpagetoday.com/special-reports/slipperyslope/54156
Rather, the benefits are metabolic. In the phase III trial -- which found that enclomiphene citrate boosted testosterone levels without lowering sperm count -- all of the participants that had secondary hypogonadism were obese. "We could not have enrolled enough men in any of the testosterone trials unless a significant number of them had an acquired disorder associated with them being overweight or obese," said Podolski. http://www.medpagetoday.com/Endocrinology/GeneralEndocrinology/54380
It's unclear whether the company will be made to perform another phase III trial before moving forward. "We need to talk with the FDA first," said Podolski, adding that it will likely take a year to define who should be treated and that the company will likely not fight the FDA over the validation issue.
"We think the FDA's willingness to talk with us, and for us to work with them in a [collegial] fashion, in the final analysis I think this makes for a better development of medicine that's clearly needed in men with low T," he said.
Method changed from Siemens Centaur XP platform to Abbott Architect i2000 platform on November 17, 2014. http://labmed.ucsf.edu/labmanual/db/data/tests/890.html
The new testosterone immunoassay on the Architect i2000 platform correlates better than the older Siemens Centaur XP immunoassay in comparisons with the UCSF LC tandem mass spectrometry testosterone assay. The new Architect immunoassay also has better low end sensitivity than the previous Siemens Centaur immunoassay and gives results that are approximately 27% higher than the previous Siemens Centaur immunoassay.
Also, please note that the reference ranges have changed.
How The 'Low T' Wars Cast A Shadow Over Repros' testosterone Alternative
Repros Therapeutics Completes Randomization of Phase 2b Study of Vaginal Proellex(R) in Women With Symptomatic Uterine Fibroid Bleeding
THE WOODLANDS, Texas, Nov. 12, 2015 (GLOBE NEWSWIRE) -- Repros Therapeutics Inc.® (Nasdaq:RPRX) today announced it has completed randomization for its Phase 2b study of Proellex® in the treatment of women suffering with symptomatic uterine fibroids. The primary endpoint for the study is the incidence of amenorrhea induced by four months of treatment with two dose levels of Proellex® compared to placebo. In addition, subsequent to discussion with the FDA, Repros is collecting an assessment of blood loss by a validated alkaline hematin method at baseline and during off-drug intervals. At baseline menses women were required to exhibit > 80 ml of blood loss by that method to be enrolled.
In addition to blood loss, bulk symptoms associated with fibroids and treatment effects on uterine and fibroid size, determined by MRI, will also be assessed.
The Company expects to have topline results from the study of the subjects' first four-month course of treatment during the second quarter of 2016.
A sister study using low doses of oral Proellex® in similar women has completed screening and should be fully randomized before the end of January 2016. Correspondingly, the topline data from that study will be available later than the vaginal data.
Is It All Over For Repros Therapeutics?
FDA cancellation of the Advisory Committee meeting citing last minute concerns has dealt a huge blow to the stock.
Cancellation was attributed to questions that arose late in the review regarding the bioanalytical method validation that could affect interpretability of certain pivotal study data.
Secondary hypogonadism definition and patient selection may be the bigger issue that some analysts are concerned about.
Repros Therapeutics (NASDAQ:RPRX) and its investors received a major blow when FDA cancelled the advisory committee meeting scheduled for November 3, 2015 to decide the approval of Androxal (enclomiphene) for secondary hypogonadism. RPRX has had to cross many hurdles with FDA over the years with respect to Androxal. Some analysts appear to have already written the obituary for Androxal .
FDA Advisory committee was scheduled to discuss new drug application for androxal (enclomiphene citrate 12.5 mg and 25 mg capsules for the proposed treatment of secondary hypogonadism in fertile men (men with more than 15 million sperm/milliliter (ml)), younger than 60 years of age with a Body Mass Index (BMI) over 25. The two studies ZA304 and ZA 305 had shown positive results in Phase III clinical trials when compared head to head with androgel (topical testosterone gel) and placebo with high statistical significance. There were no significant safety issues in trials. Out of the two deaths in the trial one was due to a traffic accident and the other due to a stroke which couldn't be attributed to Androxal. Androxal is an oral selective estrogen receptor modulator (SERM) for the treatment of secondary hypogonadism in overweight men. Unlike testosterone supplementation it doesn't cause lowering of sperm count while restoring normal testosterone levels. Recent FDA cardiovascularsafety concerns regarding testosterone therapy and the prevalence of secondary hypogonadism had given investors reason for great enthusiasm. It is believed to be an over $1 billion a year drug if approved. Institutional ownership was at 58.91% as of September 30,2015.
FDA's eleventh hour cancellation of the Advisory Committee has generated a lot of anger, disappointment and speculation. Androxal had a PDUFA date of November 30, 2015. Cancellation was attributed to questions that arose late in the review regarding the bioanalytical method validation that could affect interpretability of certain pivotal study data (whether Androxal truly met the primary endpoint in phase III trials). RPRX CEO Podolski defended the Repros-chosen lab, saying that it was CLIA-certified and a reliable conductor of the necessary assays. The pessimism stemming from FDA's decision however involves more than just the concern for bioanalytical method validation. The secondary hypogonadism definition and patient selection may be the bigger issue that some analysts are concerned about.
Male hypogonadism is a condition in which the body does not produce enough of the testosterone hormone. Primary hypogonadism is a condition that originates from primary testicular failure. Secondary hypogonadism indicates a problem in the hypothalamus or the pituitary gland - parts of the brain that signals the testicles to produce testosterone. It has many causes like Kallaman syndrome, pituitary disorders, inflammatory disorders,HIV/AIDS, Medications, obesity and stress induced to list a few. The trials were done with overweight patients in the age group 18 to 60years. Men were screened with two morning Total Testosterone measurements to identify individuals for the intent-to-treat population (ITT) by virtue of having a serum TT of <300 ng/dL (<10.4 nmol/L) and a low or inappropriately normal LH level (<9.4 IU/L). The baseline characteristics of ZA-304 and ZA-305 trials were highly and statistically consistent within studies and between studies for age, body mass index , sperm concentrations and serum TT. The conundrum however is whether these patients were screened for any of the specific causes of secondary hypogonadism mentioned above other than weight. In other words was the hypogonadism due to the patients being overweight or did some of them have other conditions too. If some of them did or didn't have other conditions then how would those variables skew the results. To cite an example would a patient with a BMI of 32 with sarcoidosis and hypogonadism experience the same benefit as a patient with BMI 32 without sarcoidosis on Androxal? Did RPRX ignore other causes and get too focused on obesity? A slide from an oldpresentation, "It's really Obesity" seems to suggest that it may be the case. If FDA is concerned about selection bias and whether true randomization was achieved then RPRX is in trouble because further studies/analysis may be needed. Logic would dictate that it would be blatantly unfair on the part of FDA to come up with this sort of objection at the last moment. History with respect to FDA though would suggest otherwise.
RPRX's financial health is not great. The company had cash and cash equivalents of approximately $26.2 million as of September 30, 2015 as compared to $46.6 million as of December 31, 2014. Approximately $20.5 million and $22.9 million was used in operating activities during the nine month periods ended September 30, 2015 and 2014, respectively. The other product in RPRX pipeline Proellex for symptomatic uterine bleeding in women with fibroids has just completed randomization for phase 2b trials and results are expected in the second quarter of 2016 per a recent press release. Proellex has already had problems with FDA in the past when FDA had put a clinical hold on the trial before lifting it in 2010. Bottom line is that investors should not consider getting in at this level. It is best to wait for FDA concerns to be better defined and what FDA expects RPRX to do to address those concerns.
Repros Therapeutics Receives Complete Response Letter From FDA for Enclomiphene
THE WOODLANDS, Texas, Dec. 1, 2015 (GLOBE NEWSWIRE) -- Repros Therapeutics Inc.® (Nasdaq:RPRX) today announced that it has received a Complete Response Letter from the U.S. Food and Drug Administration (FDA) for its New Drug Application for enclomiphene for the treatment of secondary hypogonadism in overweight men wishing to restore normal testicular function. A Complete Response Letter is a communication from theFDA that informs companies that an application cannot be approved in its present form.
In the letter, the FDA stated that, based on recent scientific developments, the design of enclomiphene Phase 3 studies is no longer adequate to demonstrate clinical benefit and recommended that Repros conduct an additional Phase 3 study or studies to support approval in the target population. The FDA also noted concerns regarding study entry criteria, titration and bioanalytical method validation in the Phase 3 program.
More BS!!! This drug is DOA.
Repros Updates Proellex® Program
Repros Updates Proellex® Program (NASDAQ:RPRX)
Repros Updates Enclomiphene Program
Repros Updates Enclomiphene Program (NASDAQ:RPRX)
- Repros expects to meet with FDA to discuss "Complete Response Letter" for enclomiphene NDA during February 2016
- Marketing Authorization Application (MAA) for enclomiphene planned for submission in Europe mid-2016
Repros Therapeutics Inc (NASDAQ:RPRX) CEO Joseph Podolski bought 11,677 shares of the business’s stock in a transaction on Thursday, January 7th. The shares were acquired at an average price of $1.18 per share, for a total transaction of $13,778.86. SEC FORM 4
[DOA] Repros Holds Meeting With FDA to Discuss Complete Response Letter for Enclomiphene in the Treatment of Secondary Hypogonadism
THE WOODLANDS, Texas, Feb. 08, 2016 (GLOBE NEWSWIRE) -- Repros Therapeutics Inc.® (Nasdaq:RPRX) today announced that on February 4, 2016, the Company attended a productive meeting with FDA reviewers and senior leaders to discuss resolution of issues identified during the enclomiphene NDA review.
The meeting agenda covered a broad range of topics surrounding the NDA data as well as emerging Agency and expert thinking regarding the treatment of hypogonadism.
The Company believes that it was clear during the meeting that the FDA is not closed to entertaining secondary hypogonadism as an indication.
Repros Completes Randomization of Enclomiphene Phase 2 Proof of Concept Study in Obese Secondary Hypogonadal Men
Repros Completes Randomization of Enclomiphene Phase 2 Proof of Concept Study in Obese Secondary Hypogonadal Men (NASDAQ:RPRX)
Repros Announces Initiation of Formal Approval Process by the European Medicines Agency
Repros Announces Initiation of Formal Approval Process by the European Medicines Agency (NASDAQ:RPRX)
THE WOODLANDS, Texas, March 15, 2016 (GLOBE NEWSWIRE) -- Repros Therapeutics Inc.® (Nasdaq:RPRX) today announced that it has formally activated the process for obtaining marketing authorization for enclomiphene in the treatment of secondary hypogonadism by the European Medicines Agency(EMA).
Repros is seeking the enclomiphene marketing authorization for Europe through a central filing which is valid in all European Union and European Economic Area countries, i.e. 31 countries in total. The centralized procedure allows for a pan-EU review of the data, led by the Rapporteur's and Co-Rapporteur's assessment teams, and is governed by set timelines; therefore the review time is well defined. Based on these timelines, the Company believes authorization to market enclomiphene in the EU can be obtained by the fourth quarter of 2017. Importantly, EU approval would open potential marketing opportunities for enclomiphene to numerous non-US territories.
INTRODUCING JOE PODOLSKI, SALESMAN OF THE CENTURY? (RPRX)
Introducing Joe Podolski, Salesman of the Century? (RPRX)
Porky Pig Pump Podolski
[LMAO] Repros Announces New CEO
Repros Announces New CEO
Repros Therapeutics Inc.® (RPRX) today announced that [CON MAN] Joseph S. Podolski is leaving his position as President and Chief Executive Officer and member of the Board of Directors to pursue other interests.
Company Holds Meeting with FDA to Discuss Oral Proellex® in the Treatment of Uterine Fibroids
THE WOODLANDS, Texas, April 10, 2017 (GLOBE NEWSWIRE) -- Repros Therapeutics Inc.® (Nasdaq:RPRX) today announced that the Company held a meeting with the FDA to discuss the progress and next steps in the development of Proellex® (telapristone acetate) for the treatment of uterine fibroids.
Shortly before the meeting, the Company was notified that the meeting would be a type C/Guidance meeting, rather than a type B/End of phase 2 meeting as previously anticipated.
At the meeting, the FDA confirmed that Proellex® will continue on the current partial clinical hold while they consult with liver experts within the FDA regarding previously disclosed effects on the liver.
Further, the FDA agreed to accept additional information from the Company and its panel of liver experts for consideration by the FDA's internal advisory liver team.
The Company expects to submit the additional information and a proposed clinical protocol within a month. The Company intends to announce further information following receipt of additional guidance from the FDA.
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