- Here are my notes from the OPTR conference call this morning 5/31/11 to discuss the FDA approval of Dificid (fidaxomicin):
- Superiority in sustained clinical response over vancocin recognized in label (lower rate of proven or suspected recurrence)
- C. difficile associated diarrhea (CDAD) associated w/ increased length of hospital stay and increased healthcare costs
- avg CDAD episode can cost up to $17,000 or more...cost $3.8b per year in US healthcare system
- Cubicin price $900-1800, up to $8000 for bacteremia
- Zyvox $2800 for bacteremia, up to $5600 for BRE infection
- vancocin $1000-1500, about 50% receive higher dose or longer duration = higher drug costs
- OPTR has set the Dificid WAC at $2800 for 10 day course
- nearly all payers/ plans surveyed said they would put on tier 3 or better at this price
- With Cubist $CBST, will launch Dificid early in 3q11 - about 6 weeks from now. OPTR will have hired the majority of planned 100 reps by then
- q&a session:
- Do you expect first line use? Will be positioned for first line therapy, especially in high risk pts- economic and patient benefits far superior to current options
- 450k annual cases of CDAD reported in hospitals. Estimate that there are an additional 250k afflicted, some estmates as high as 3m per year.
- Believe high risk portion of mkt is 70% of patients
- post marketing trials and surveillance? Will do studies in pediatric indication and looking at multiple recurrences. Also will have a surveillance programs...Still in discussions on details of these-have tieline of when to submit protocols for the studies to the FDA
- OPTR does not believe it makes sense to do trial comparing to flagyl. metronidazole is not an approved drug for this indication and has serious deficiencies in cure rate. >20% fail and an additional 27-30% fail in recurrence. This product is consistently losing sales to vancomycin.
- Do you expect near term use in prophylaxis? In process of doing retrospective studies to determine incidence of CDI in an appropriate pt population- need this info to design trial. For example, pts w/ hospital pneumonia and have broad spectrum abx (3x different), mostly in ICU. This represents 20% of total CDI pts. Could tx with Dificid initially during 14 days of pneumonia tx and the continue for some period of time afterwards. But need better idea of incidence in this pop (estimates range from 7-24%)
- Discrepancy between the two phase 3 trials? one trial noninferior. one trial clearly superiority to vanc. in subpopulation with BI strain. OPTR don't have explanation except that trial not powered to detect differences in any such sub-populations.
- It is not feasible to screen Cdif strain before tx. Strains also change over time. It is not clear when or if there will ever be clinical practice based on the given strain a pt has.
- Won't disclose COGS at this time. "pharmaceutical margins" Don't see much difference in margins between yr 1 to yr 2
- With $2800 WAC, could end up with net sales 15-25% lower that than per pt after rebates, etc
- Method of use patent thru 2027 (OPTR says this is strongest protection they have). Isomer patent to be issued in relative short term. Other polyform A patents in place thru 2025, 2026
- There is an option by both parties to extend CBST deal
- All market research surveys asked question re if vancocin goes generic- won't impact Dificid market. 80% of vancomycin use is already in form of generic slurry. No motivation on part of payers to remove dificid from tier 3
- Not doen w/ studies to determine pricing in europe, but antibiotic prices in Europe are significantly lower than US
- No financial guidance until company sees rate of launch
"This study had no financial disclosures (so it was done independently and should be unbiased); I think it will be hard for the FDA to claim this isn't a disorder."
I pulled the abstract he referenced- here is the full text:
Monday, May 16, 2011 10:30 AM-12:30 PM
911: SCREENING FOR HYPOACTIVE SEXUAL DESIRE DISORDER (HSDD) IN THE UROLOGY OFFICE SETTING
Michael Ingber, Tianming Gao, Howard B Goldman, Denville, NJ
INTRODUCTION AND OBJECTIVES: HSDD is the most common sexual desire disorder found in women. Multiple comorbidities may contribute to low sexual desire, specifically those found in women seeking care from a urologist. Our objective was to determine the prevalence of low sexual desire in women presenting to the urology office for a variety of reasons. A secondary objective was to determine factors that may contribute to having low desire. METHODS: This was a prospective study of female patients presenting to the urology office for any reason (stones, hematuria, prolapse, incontinence, etc.). Female subjects over the age of 18 were offered the Decreased Sexual Desire Screener (DSDS). Patients answering "yes" to the first 4 questions on the DSDS represented the cohort qualifying for a diagnosis of HSDD, pending physician evaluation to see if any other factors (listed in item 5 on the DSDS) can impact low desire. Demographic factors as well as diagnosis codes were recorded and analyzed. Descriptive statistics, univariate and multivariate logistic regression were used in order to determine any predictors of low desire.
RESULTS:Overall 339 women completed the DSDS. 273 (81%) had a decrease in sexual desire, with 95 (28%) qualifying for a possible diagnosis of HSDD by answering "yes" to items 1 through 4 on the DSDS. Women between the age of 41 and 52 were most likely to qualify for a diagnosis of HSDD with 37% of this age group qualifying. Factors such as marital status, employment status, race and BMI did not contribute to low desire, nor did diagnosis code. The presence of low sexual desire was common among women presenting with stones, incontinence, prolapse, infection, retention, pain, voiding dysfunction and malignancy. No one diagnosis code was predictive of women having low sexual desire or HSDD.
CONCLUSIONS:The presence of low sexual desire is common in all women presenting to the urology office. Specifically, women between the ages of 41 and 52 are at an increased likelihood of having a diagnosis of HSDD. Because many women are hesitant to bring up these complaints, urologists should be aware of sexual desire issues and question their patients on sexual function.
This presentation underscores that HSDD is a common phenomenon in the female population, as both BPAX's research, other journal articles, and an FDA advisory panel have stated.
"I realize BPAX is going after post-menopausal patients in their study, but this was still very high number."
You are correct that BPAX is going after the menopausal population. While the safety study is being completed in older (>50 yrs) women, the two phase 3 efficacy trials are in surgically menopausal women as young as 35 yrs old, so the age range highlighted in the abstract has a great deal of overlap with a potential Libigel label.
"As a physician, i don't think a small amount of testosterone is going to have significant side effects and especially in any type of study looking at 5 yr outcomes. The FDA are always unpredictable, so no one know for sure, but i think this has a great shot. The FDA will be pressure to approve a "female viagra", even though testosterone works much different that viagra. Men use testosterone all the time and this is a growing market; men probably have a lot higher risk of prostrate cancer than women have of developing any cancers (and it may actually lower their risk of cancer (but probably slightly increase risk of heart problems over the long term); looks like bpax is being smart and really getting all the studies that the fda may want ; they should be nearing full enrollment."
I agree with your conclusions- I feel that the clinical risk for both the safety and efficacy trials is quite low for Libigel compared to the average phase 3 program. They have over a thousand women who have been taking the gel for over a year, so I would be shocked to see a harmful effect appear at this point since the data safety monitoring board has been meeting so frequently. The point that male ED patients have had treatments available for years is frequently brought up by BPAX and is valid, so long as BPAX successfully jumps thru the hoops that the FDA has laid out. The safety study will be completely enrolled no later than August 2011. It is important to remember that the dose of testosterone in Libigel is orders of magnitude lower than the doses in male testosterone products- which is why they are difficult to use off-label for women and another reason why serious safety concerns in the Libigel pt population is unlikely.
"Not sure when bpax bumps, but probably not significantly until after fda approval. Their move to get fda approval for their men's gel is probably to see what problems the fda may raise with their delivery system prior to submitting for the women. Looks like a smart move!"
Clearly BPAX has had a significant bump in share price from <$2 to near $3 recently. I think the completion of enrollment in safety trial and data from efficacy trials have the potential to be additional catalysts, but I am not sure by how much it could appreciate before approval or partnering. It is important to note that the male Bio-T-Gel product developed by Teva and BPAX is not based on the same technology as Libigel, so this product has little bearing on the FDA review of Libigel. However, BPAX did get an estrogen gel product approved by the FDA that is based on the same Antares Pharma gel technology as Libigel.
"I am convinced this is the next provenge, the only difference is that testosterone in women actually works; provenge really doesn't work that well and i couldn't believe they got approved! I've never written before, so i guess i'm supposed to state my disclosure; i am "long" on bpax"
I'm not sure Provenge is the comparison I would make, but I can see it in that if Libigel is approved and becomes a success, it will have navigated a long and difficult road against tall odds and with many doubters. Note of course that more hurdles remain for Libigel (the least of which are the clinical trial data), as they do for Provenge before $DNDN will have grown into its current market valuation.
Thanks again for the comment Bill- will be an interesting story to follow the next couple years