The FDA does not do a benefit/risk analysis, but determines efficacy and safety. This might be just semantics for some, but this is a statutory requirement for the FDA. RPRX did not determine that LFT > 3X ULN was an unacceptable risk. This is a predetermined threshold for safety. LFT ULN is a well-described safety factor.
Repros believes that the decision to move forward with the 25 and 12.5 mg doses will improve the benefit/risk profile of Proellex.
“Drug development is a dynamic process, the aim of which is to try and bring to market a product with an optimal balance between benefits and risks that will address an unmet medical need in patients. Our decision to stop the 50 mg dose supports this concept, as well as demonstrates our commitment to safeguarding the well-being of the women participating in our clinical trials,” stated Dr. Paul Lammers, President of Repros Therapeutics.
Regardless of efficacy, other safety factors are unscheduled bleeding and procedures. These adverse events resulting from endometrial thickening. This is admitted to by RPRX.
In their own presentations, RPRX details these events to occur in relation to treatment duration or endometrial thickness. Both do not need to occur for these adverse events – only one is sufficient. What is more telling is that these adverse events occur after drug administration and they occur at each dose – 12.5, 25, and 50. This fits very well with the hysterectomies in the phase 2 Endometriosis trial. Not until there is an explanation for these procedures, I will assume the worst. This is more than a coincidence.
In RPRX presentation data (12.5 mg), the endometrial thickness at 120 days (4 months) was a median thickness of 17 mm. This is the median, not mean. Fifty percent of patients treated with 12.5 mg Proellex at 4 months have an endometrial thickness greater than ~17 mm. From the graph, an endometrial thickness ~18 mm demonstrates an increasing Maximum Bleeding Score. There will be a significant number of patients at 4 months with an endometrial thickness >18 mm. From Mutter's article, in both 12.5 and 25 treatment arms at least 15+% have a thickness over 20 mm.
In RPRX own words, “Prevention of normal endometrial shedding in premenopausal women treated with Proellex results in histological changes which may results in unscheduled bleeding.”
In case one did not read the above, RPRX repeats the warning that severe and unscheduled uterine bleeding occurred when the endometrial thickness exceeded 20 mm.
RPRX does admit facts. What RPRX does not do is to pull these know safety factors together and report them in a timely fashion. The LFTs are a start, now reveal the rest.
The PR admits dosing in 400+ patients. It is time they come out and categorically state that there was no (NONE) unscheduled bleeding or procedures. If there were any, admit them and let the chips fall.
They would rather have you know they are “safeguarding the well-being of the women participating in our clinical trials” by determining the benefit/risk. It is safety, not risk.
AI
