MI - any thoughts on Fis./Endroxal ?
I'm looking for the exact results of study below,
especially for ED, Apricus chose ED and libido for the first indication, Repros didn't think
they could prove those indications in 2nd HG with Endroxal, and went with metabolic benefits in outside studies with TRT, a big mistake, Apri did not make that mistake, do you think that Fis. has an anti-inflammatory aspect that could make the difference,
Info on Fis.
 https://clinicaltrials.gov/ct2/show/NCT00415571Efficacy and Safety Evaluating Fispemifene in the Treatment of Hypogonadal Men With Erectile Dysfunction Unresponsive to PDE5 Inhibitors QuatRx Pharmaceuticals Reports Positive Results From a Phase 2 Trial of Fispemifene.
Trial results indicate that the novel, oral, selective estrogen receptor antagonist significantly increases testosterone in androgen-deficient men by up to 78% in four weeks.
ANN ARBOR, Mich., Jan. 8, 2007 /PRNewswire/ -- QuatRx Pharmaceuticals today announced positive results from its Phase 2 clinical study of fispemifene in men with low testosterone levels. Fispemifene is a new, selective estrogen receptor antagonist that is being developed as an oral treatment for testosterone deficiency and associated disorders in men. Symptoms of low testosterone include sexual dysfunction, muscle wasting, reduced bone density, lowered energy levels and glucose intolerance. Unlike current exogenous testosterone treatments, fispemifene is administered orally once daily and is designed to use the body's natural mechanism to increase and maintain testosterone levels within the body's normal physiologic range.
J Pharmacol Exp Ther. 2008 Oct;327(1):58-67. doi: 10.1124/jpet.108.139501. Epub 2008 Jun 26.
Fispemifene [Z-2-{2-[4-(4-chloro-1,2-diphenylbut-1-enyl)-phenoxy]ethoxy}-ethanol], a novel selective estrogen receptor modulator, attenuates glandular inflammation in an animal model of chronic nonbacterial prostatitis.
Yatkin E1, Bernoulli J, Lammintausta R, Santti R.
Author information
Abstract
The anti-inflammatory and antiestrogenic action of fispemifene [Z-2-{2-[4-(4-chloro-1,2-diphenylbut-1-enyl)phenoxy]ethoxy}-ethanol], a novel selective estrogen receptor modulator (SERM), was tested on the Noble rat model of chronic nonbacterial prostatic inflammation with cellular composition and inflammation patterns similar to those described in human prostatitis. Inflammation was assessed by counting perivascular and stromal infiltrates and the number of inflamed acini. Furthermore, the aggressiveness of inflammation was assessed on the basis of the relation of lymphocytes to the acinar epithelium. The immunohistochemical expression of progesterone receptor (PR) and Fos-related antigen 2 (Fra2), prolactin concentration in serum, and the weights of the seminal vesicles and pituitary glands were used as endpoints of estrogen action. Fispemifene significantly attenuated the glandular form of inflammation induced in the dorsolateral prostatic lobes (DLP) in the hormonal milieu of the decreased androgen/estrogen ratio. The anti-inflammatory action was seen in the decreased number of acini containing intraluminal neutrophils. As signs of antiestrogenic action,fispemifene blocked estrogen-induced expression of PR and Fra2 in the acinar epithelium of the DLP, and it decreased prolactin concentration in serum and the relative weights of the seminal vesicles and pituitary glands. Because fispemifene exhibited both antiestrogenic and anti-inflammatory action in the prostate, this experimental study suggests that SERMs could be considered as a new therapeutic option in the treatment and prevention of prostatic inflammation.
PMID: 18583549 [PubMed - indexed for MEDLINE] Free full text
Also look at the new slide in the Apri presentation: Repros got the same guidance but chose a different path,
FISPEMIFENE: FDA Guidance Unchanged for Almost a Decade
Therapy with fispemifene is not considered to be testosterone replacement therapy. Therefore, pharmacokinetic endpoints such as total testosterone could not serve as the primary basis for approval for fispemifene. Instead,
clinical benefit for a specific disease condition would need to be demonstrated using clinical endpoints. The specific clinical benefit demonstrated in a clear target population would ultimately need to outweigh the risks in that population.”
QuatRx FDA Meeting Minutes, January 2006
“As we have previously informed you, in order to support efficacy for the proposed indication, you would need to show a clinical benefit of fispemifene on
ameliorating the signs and symptoms of hypogonadotropic hypogonadism in adequate and well-controlled clinical studies.”
Apricus FDA Meeting Minutes, February 2015 |
