- very exciting news for company and stockholders...continue development of libigel. after months of careful deliberations by management and BOD, analyzed libigel and other strategic alternatives (50x biotech/pharma in-license or merger optons) - libigel has best long-term upside
- initiate 2 new phase 3 trials - confident we've identified a numebr of substantive design changes to minimize placebo effect.
- plan to submit new protocol to FDA for comment and request SPA. same endpoints
- previous trials - showed 90% decrease in distress and increase # SSE
- potential things to change: minimize interaction with sites, scripting interaction with sites, fewer visits to sites, changing frequency of diary reporting, maximizing # SSE at baseline, maxmizing T levels at baseline
- hope to submit 3q2012 for SPA, initiate late 2012 or early 2013
- also continue to invest in safety trial. Average subject age just over 60. 6500 pt years. ranging 1-4 yrs on drug, avg 22 months. 20% smokers, 20% diabetes, 60% hypertension or high cholesterol
- top-line safety data by ye-2012
- projected cost of new trials $15-18m each or $30-36m total spread over period of approximately 18 months
- $11.8 m notes outstanding.
- good financial position to LAUNCH new trials
- why is this the best course? most other opportunities were inlicense. plus reverse mergers/mergers. and we continue to look at some of those. may in-licence other products over time. key question: could we convince ourselves and outsiders that new trials would have different outcome.
- safety study being conducted at FDAs request, but they have no inlfuence on decision to continue (analyst misheard earlier statement)
- bear cost of safety study thru 2016. Patients come in 4x first year, then once per year, so costs decrease. also each woman completes after 5 years. $2.5m per month is cost of study and the primary analysis.
- top Libigel trial change would be frequency of diary reporting. each change additive, would be optimal to change one this at a time, but we obviously can't do that
- looking for differences in baseline pt characteristics? basic requirement is menopausal. one other change - previously could be on or off estrogen. this time cannot be on estrogen. will increase rate of patient enrollment because easier to find women off of E vs on [this statement makes no sense]
- why so important to get another SPA? what if you dont get it? best comments from FDA come from formal statutory SPA application process. if have diasgreemnt, want to get it on the table and negotiate away the problem.
- range in cost is ad expense due to relative ease of enrollment. he thinks will be easier this time [Why? After failing the first time?]
- enroll in 6-9 months, then 6-8 months from last woman enrolled to finish studies
- safety now costing $1-1.5m per month depending on number of visits. use $1m/month ongoing for next year or so
- placebo reached its max in about 1st month of treatment
- Kingsberg published paper saying that daily diaries are not as effective. So why did we? FDA wanted it. we had no reason not to at the time. fda ok with switch? we believe that is the case. confirmed or not when request SPA and get comments.
- Have you met with FDA since libigel trials' failure? yes
- met with same consultant this time vs those that recommended daily diaries originally? 2000 guidance document had suggestion of daily diary. now division director retied end of 2011, new acting director. but one of key people in division has been same from 2000 to now. she was one of FDA presenters at 2004 Intrinsa panel.
- won't comment of specifics on discussion. we are confident that they will change the frequency, weekly is one possibility. wouldn't embark on program if we weren't confident they would go along.
- consider 30 day placebo run-in and exclude those with excessive responses and then randomize? 1 month max was seen with intrinsa trials. our data showed continued increase in months 3-4. run-ins "all of those are under consideration" - FDA has issues with eliminating "good responders"
- patent life? two issued and expiring 2022 and 2028.
- data driven reason for FDA daily diary request? i would let FDA comment on that. probably what "patient-reported outcomes" people recommended to them. intrinsa 5000 pts, 4000 women years, plus our data, indicate that daily diaries not appropriate for this population
- max enrollment rate in old studies? how will rate be affected by objective to reduce palcebo effect? 6-9 months, hope faster. safety study is all comers. but inclusion/exclusion (smokers, diabetes) criteria for efficacy studies. Exact enrollment data from past trial "don't have in front of me" - not relevant because enrolled into safety study at same time. we think we'll be more efficient this time
- expect more screening failures? no that is not true. failure rate not higher for these than previous effiacy tirals [but analyst's point was higher failure compared to safety study]