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Hmmm...reconcile these two statements in the 10-Q
In the earnings announcement, Titan mentioned Braeburn had reimbursed it for development expenses. Why? Is this a clue?
From Note 5 to Financial Statements, "Braeburn License"
"Following FDA approval, we will be reimbursed by Braeburn for any developments services and activities undertaken by us at Braeburn’s request."
From Item 2, MD&A
"The decrease in research and development costs was primarily associated with the reimbursement of expenses by our development partner, Braeburn."
Old news, but the thing I hadn't focused on with respect to the societal impact study was that it compared a world where all patients were implanted with probuphine vs. a world where all patients were taking SL buprenorphine.
So, the benefits don't measure probuphine vs. no treatment at all. They measure incremental improvements to society if probuphine was used in place of SL buprenorphine. They include: "an overall 45% reduction in treatment failure over 6 months of treatment. Modeled reductions in societal-level consequences were: opioid diversion and misuse (-92%), illicit drug use (-45%), accidental pediatric exposure (-98%), detox program entry (-80%), and drug-related death/suicide (-24%)."
Societal Impact Study Abstract
http://www.amcpmeetings.org/pdf/meetingabstracts.pdf
Subdermal Buprenorphine Implants Improve Societal Outcomes and Patient Morbidity and Mortality Relative to Sublingual Buprenorphine: Results of a Markov Model
BACKGROUND: Agonist therapy reduces cravings and relapse risk during recovery from opioid dependence. Fewer relapses equate to reduced societal consequences such as illicit drug use, disease transmission, criminal activity, mortality, and harm to community members. Sublingual buprenorphine+naloxone (SL-BPN), the standard-of-care in outpatient opioid dependence treatment, lacks intrinsic safeguards from diversion and non-adherence. Investigational subdermally implanted buprenorphine (BI, Probuphine) was more effective than SL-BPN in Phase-3 clinical trials, including a large double-blind, double-dummy trial in stable opioid-dependent patients. The extent that these clinical benefits translate into meaningful societal benefits has not been previously quantified.
OBJECTIVE: To assess the benefits of SD-BP from a societal perspective.
METHODS: Using Phase 3 clinical trial data of BI versus SL-BPN, a Markov model simulated monthly progression of nationally-representative cohorts through 5 health-states for 6 months: on agonist therapy (1) with and (2) without illicit drug use, discontinued therapy (3) with and (4) without illicit drug use, and (5) death. Each cycle applied health-state- and time-dependent risks of: opioid diversion and misuse, illicit drug use, accidental pediatric exposure, detox program entry, and death (suicide/drug-related non-suicide). Cohorts were derived from state-specific, agonist treatment utilization data. Model robustness was assessed by univariate and probabilistic sensitivity analyses.
RESULTS: BI was associated with an overall 45% reduction in treatment failure over 6 months of treatment. Modeled reductions in societal-level consequences were: opioid diversion and misuse (-92%), illicit drug use (-45%), accidental pediatric exposure (-98%), detox program entry (-80%), and drug-related death/suicide (-24%). A Statewise comparison demonstrated the greatest benefits for Pennsylvania and the fewest benefits for Idaho.
CONCLUSIONS: Benefits of BI vs. SL-BPN included improved morbidity/mortality and improved societal-level outcomes. Benefits were largely driven by the relative difficulty of diverting an implantable formulation. Patient-level benefits may be driven by the increased adherence and pharmacokinetic profile of the implants. While these results should be confirmed in subsequent studies, it can be conservatively concluded that BI treatment used for stable opioid dependent patients will have a positive societal benefit beyond the current standard of care.
SPONSORSHIP: Braeburn Pharmaceuticals.
Cigna and Addiction Specialists Team Up to Study Which Treatments are Working
I hope the efficacy results from probuphine's Phase III are included in their analysis!!!
https://www.ncadd.org/blogs/in-the-news/cigna-and-addiction-specialists-team-up-to-study-which-treatments-are-working
The health insurance company Cigna is teaming up with the American Society of Addiction Medicine (ASAM) to study which substance abuse treatments are effective, Forbes reports.
The company will provide two years of medical claims data to ASAM, who will work with health researchers at Brandeis University to test and validate which treatments are working. All patient names have been removed to ensure confidentiality.
The results could be used to develop guidelines for Cigna and other health insurers to establish protocols for doctors and other mental health providers, the article notes.
“When it comes to substance abuse, there are not clear guidelines,” said Dr. William Lopez, Cigna’s Senior Medical Director for Behavioral Health. “Our position is that we want to individualize the treatments and by having some guidelines that are more holistic, we will attain that goal. We want to move from volume to value.”
He explained researchers hope that analyzing medical claims will allow them to determine which patients may have had re-admissions to hospitals for drug abuse. If patients who are at high risk of relapsing are identified early, insurers and doctors might be able to intervene at an earlier stage, he said.
“We can drill down in the data and develop some predictive models,” Lopez said. “This is a chronic disease and they may struggle with this for years. We can use this data to better manage (their care).”
“This will encourage physicians to make significant improvements in the quality of patient care for the addiction field as well as in the healthcare system as a whole,” Dr. Corey Waller, Chair of ASAM’s Performance Measures Expert Panel and Legislative Advocacy Committee, said in a statement. “This will encourage physicians to make significant improvements in the quality of patient care for the addiction field as well as in the health care system as a whole.”
I hear you. The selling hasn't been all that concerning in terms of number of shares, but our float is so small that even a relatively small percentage of the total number of shares outstanding can have a huge impact. But that's a two-sided sword, and hopefully we see appreciation just as quickly in the days to come.
There may be some sort of concerted effort on the part of short sellers to take out stop orders, but I sense a lot of the selling was from momentum players that weren't going to hold into the PDUFA date anyway. They will be back in the minute things start going North again. Other long-term holders may be selling out of sheer frustration or fear. Call it whatever you like, holding Titan is not for the timorous.
I actually feel bad for those who have held for a long time, and then sell at 5 and change and then wake up to find the bid opening at $12 to $15 once approval is announced. Then again, they could be feeling bad for me if a CRL is announced. Time will tell...
Well, if this is a bear raid it appears to be working. Perhaps Sheff cut bait as well.
Also, Kempharm (KMPH) had an Ad Comm which voted for approval of their opioid for pain but against allowing an abuse deterrent label...probably good for Titan (because what's more abuse deterrent than an implant!) but fear doesn't allow for the most nuanced of market reactions.
Also, ENDO (Biodelivery Science's partner on buprenorphine film) revised their earnings guidance down and took a huge hit (BDSI is down also). Again, if the film isn't selling well, that's good for Titan (it's not like their has been a reduction in patients!) but I think Titan is getting thrown under the omnibus opioid bus today.
Yes, the volatility on such a small number of shares traded is maddening...but hopefully it works both ways. Perhaps any run up to the PDUFA date is over? I think a lot of folks are nervous (I am). ENDO cratering doesn't help.
I wonder why that took them so long to post? And who is the intended audience? At first I thought it was nudging the FDA, but the study was probably planned months ago. Maybe the insurance industry to try to get probuphine covered (when generic pills are available)? Less costs for drug overdoses, rehab treatments, etc. Then again, what do I know.
FDA Panel Urges Mandatory Opioid Training for Doctors
http://www.wsj.com/articles/fda-panel-urges-mandatory-opioid-training-for-doctors-1462405146
By THOMAS M. BURTON
May 4, 2016 7:39 p.m. ET
39 COMMENTS
WASHINGTON—An advisory panel to the Food and Drug Administration overwhelmingly endorsed mandatory training for doctors who prescribe opioid painkillers, in an effort to stem what has become a national epidemic of deaths and addiction from the drugs.
The recommendation followed a two-day hearing on the medical evidence regarding opioids and ways to improve their safety. Overall, the committee voted unanimously to recommend an overhaul of current federal requirements to train doctors and patients about the risks of overusing the pain drugs.
On the mandatory doctor-training question and some other safety recommendations, the panel’s chairman, Dr. Almut Winterstein of the College of Pharmacy at the University of Florida, said the group had shown “fairly overwhelming agreement.”
“We need to teach people to use these drugs sparingly,” said committee member Jeanmarie Perrone, a professor of emergency medicine and toxicologist at the University of Pennsylvania.
The Centers for Disease Control and Prevention estimates that as many as 19,000 Americans die from narcotic painkillers annually, a number that has been rising for at least the last 15 years. The products involved include medicines that contain hydrocodone, oxycodone, morphine and fentanyl.
They are often given to people with severe postsurgery, cancer and other pain, but many addiction specialists say they are given too often to people with chronic pain.
The FDA often follows the recommendations of its outside panels of medical experts, but it doesn’t have to. Convening the panel is one of several steps taken by the agency on opioids since Dr. Robert Califf became FDA commissioner in February.
The committee acted after hearing extensive public testimony that making opioid training mandatory for doctors was important, and that it shouldn’t be controlled by the drug industry.
Sidney M. Wolfe of the Washington-based consumer group Public Citizen called for “mandatory training and testing to get a narcotics license with as little opioid industry involvement as possible.” Physicians, said Dr. Wolfe, are “too often influenced by opioid industry-funded ‘education’ and promotion.”
Testifying before the panel, Chris Johnson, an emergency medicine doctor in Minneapolis, said: “Every brain is at risk for dependence. As far as the human brain is concerned, all opiates are heroin.” The only way to reduce patient addiction and overdoses, he said, “is to reduce opioid prescribing.”
Well, as the song goes, the waiting is the hardest part. I'm glad that this month I'll finally know one way or the other, because quite frankly this has been exhausting.
I've given up guessing on a price upon approval, because the market appears to be bat$&@# crazy.
249 Days down....
23 to go. August 31st 2015 (announcement of resubmission of NDA) seems a long time ago.
Synergies
Braeburn is owned by Apple Tree Partners, who also owns...
http://www.appletreepartners.com/portfolio/detail/cleanslate-addiction-treatment-centers
http://cleanslatecenters.com/
New form of Buprenorphine — implant
Nice to see this catching on with treatment centers...
https://www.savannahoutpatient.org/new-form-buprenorphine-implant/
This speaks for itself:
Braeburn Pharmaceuticals said there is already strong interest in Probuphine. About 4,000 doctors have already signed up to ask to be trained in how to implant and remove the drug. While 28,000 doctors are federally authorized to prescribe buphrenorphine, only about 6,000 write about 90 percent of the total prescriptions in the U.S.
Thanks for posting Truth.
...uh, math was never my strong suit.
I meant to conclude the post saying $4,000 x 203,000 would be $812 million in sales at 50% penetration of the addressable market of patients stabilized on an 8mg dosage of buprenorphine. At 25% penetration, there would be $406 million in sales. Napadono's estimate of $150 million in sales means 18% penetration.
Numbers...
Only if you're bored of watching the paint dry...Interesting report on SA about Titan. Came away with a few thoughts:
-Current US buprenorphine market is around $1.8 billion.
-Cost of two months of 8mg SL buprenorphine film is around $460, for an annual drug cost of $2,760. Divide that into $1.8 billion (assuming everyone was taking tablets or the film), and you get around 650,000 patients.
-With the TREAT Act passage or HHS revision of prescription regulations, number of allowed buprenorphine prescriptions should expand from 30 to either 500 or 100. Anyway, let's conservatively say the number of patients increases by 33% from 649,000 to 864,000 patients.
-What is the real cost of care to an insurer? SL buprenorphine is $2,760 per year, plus monthly office visits (estimate $130). Total annual cost $4,320.
-I've heard probuphine will come in around $2,000 a treatment. So $4,000 a year, plus two office visits for insertion removal at $350 a piece (based on Implanon implant cost estimate). So the total cost is $4,700 per year.
That's a lot damn closer than I thought...and a lot less potential liability for the prescribing doctor for failing to keep up with records, office visits, etc. Oh, and did I mention it can't be abused?
A Braeburn study of 642 random SL buprenorphine users showed 47% of patients were using 8mg or less dosing. 47% of 864,000 patients would be a potential market of 406,000 patients. 50% of that "submarket" would be 203,0000 patients.
$2,000 x 203,000 =$406 million a year in sales. Not counting off-label chronic pain.
Still, Napodano says he sees sales peaking at $150 million because of restrictive REMS...but what's more restrictive than monthly visits? And if the price is close, it seems a no brainer.
New implant set to join fight against U.S. painkiller epidemic
http://www.reuters.com/article/healthcare-titan-pharma-idUSL3N17U3NN
Two companies are on the cusp of taking a new treatment for opioid addiction to the U.S. market at a time when lawmakers are seeking ways to arrest an epidemic of heroin and painkiller abuse that kills 78 Americans every day.
Titan Pharmaceuticals Inc and privately owned Braeburn Pharmaceuticals have together developed a matchstick-sized implant that analysts expect will be approved next month, despite mixed reviews.
Implanted into the arm, the treatment is designed to be less vulnerable to abuse or illicit resale than the oral drugs that are currently used to treat opioid addiction.
The market for the implant could also be much bigger than first envisaged should a bill gaining bipartisan support on Capitol Hill become law. The bill aims to raise limits on the number of addicts that an individual doctor can treat.
Drug overdoses have overtaken motor vehicle crashes and firearms as the leading cause of injury-related deaths in the United States, the U.S. Drug Enforcement Administration says.
Of the estimated 2.2 million Americans who need treatment for abuse of heroin or prescription painkillers, fewer than half are receiving help, according to the U.S. Centers for Human and Health Services (HHS).
This has become an issue in the U.S. presidential campaign, and experts say there is a strong appetite for updated legislation. President Barack Obama is already pushing for $1.1 billion in new funding to expand treatment.
Two drugs are predominantly used to treat opioid addiction: methadone, which is dispensed only in government-endorsed clinics, and the less-addictive buprenorphine, which exists as a pill or strip of film.
The implant, known as Probuphine, offers an alternative by administering buprenorphine for up to six months after users have first been stabilized on the oral form of the drug.
It was developed by Braeburn, owned by New York City-based venture capital firm Apple Tree Partners, and Titan, a San Francisco-based developer of proprietary therapeutics.
"This epidemic isn't going away," Braeburn Chief Executive Behshad Sheldon said in an interview. "No matter who is in the White House or Congress, there is going to be a continual push to come up with new and innovative solutions."
Staff at the U.S. Food and Drug Administration have raised reservations about possible complications from the insertion and removal of the 26mm (1-inch) long implant. Trial data has also shown that some users still need oral buprenorphine.
However, an independent panel of experts to the FDA has voted largely in favor of the treatment. Given the size of the epidemic, analysts say they expect FDA approval by May 27.
Other companies could also enter the market.
Indivior Plc, spun off from British consumer goods company Reckitt Benckiser Group Plc, has a buprenorphine injection in a late-stage study.
Raleigh, North Carolina-based BioDelivery Sciences International Inc, which already sells buprenorphine film, is also working on an injectable.
WAITING LISTS
Despite recent guidelines to prescribe fewer opioids for pain relief, the U.S. market is expected to grow to $18 billion by 2021 from $11 billion in 2014, according to GBI Research.
Yet fewer than 30,000 of the country's 800,000 or so physicians are eligible to prescribe buprenorphine for addiction, according to the National Alliance of Advocates for Buprenorphine Treatment.
Under current law, a doctor can treat only 30 addicts within a year of obtaining a waiver, rising to a maximum 100 after procurement of a second waiver.
This is done to minimize the risk of illicit redistribution, as well to ensure an adequate level of care for each patient. But opponents argue that it has left the healthcare system unable to cope with the rising number of addicts.
"Even at 100, all of us that are active in the field still have a waiting list," said Dr. Richard Soper, chief medical officer of the Nashville-based Center for Behavioral Wellness.
A bill called The Recovery Enhancement for Addiction Treatment (TREAT) Act aims to change this. It includes a provision to raise the patient cap to 100 in the first year and 500 thereafter.
It would also exempt from the cap any treatment directly administered by a physician - such as an implant or injection.
Backed by Republican Senator Rand Paul and Democratic Senator Edward Markey, the bill won the unanimous backing of the U.S. Senate Health, Education, Labor and Pensions Committee on March 16. Since then, Titan's shares have risen more than 70 percent.
To be sure, the bill's passage is far from assured.
Should it falter, a plan B exists in the form of a proposal by the Centers for Health and Human Services to raise the patient limit to 200, which would not require congressional approval. (1.usa.gov/22KJI0S)
However, the cap would still begin at 30 and would rise to 200 only in stages - not enough to make a significant difference in the eyes of drug developers. (Reporting by Natalie Grover in Bengaluru; Editing by Robin Paxton and Ted Kerr)
Tennessee Pain Clinics to Stop Using Opioids
http://www.painnewsnetwork.org/stories/
So the immediate fall out from the FDA's new opioid guidelines is at least one state saying..."OK, &$%@ this, no more opioids." Which will lead to more abuse, black market sales, counterfeit drugs, suicides, overdoses, etc.
And probuphine is not approved.
I have no more words. Just disgusting.
That doesn't count any premium for technology or pipeline.
...or even the full value of probuphine, including expansion to chronic pain, milestone payments, rest of the world licensing deals, etc.
Take away all the press releases, conferences, summits, speeches...basically take away all the words (to quote Shakespeare..."sound and fury, signifying nothing"...), and all that is left is actions.
The FDA's actions don't need words, they speak for themselves.
Yeesh...I'm starting to feel the only way probuphine gets approved is if I sell my shares. Apparently I was very bad in a past life (hope I enjoyed myself at least), because the laws of karma say approval would be announced the minute after I sold.
Yeah, over the past week or so I had gotten used to having some after-hours trading every day...but nothing today. Any significance?
Hey Turks, I think the p.r. Titan released was on probuphine Phase III data. This looks to be a separate study that Braeburn commissioned that basically looks at the responder rates based on the Phase III studies, and extrapolates that out to a world where probuphine was approved. In that hypothetical scenario, Braeburn's study found that for patients that switched over to probuphine, there would be a reduction of overdose deaths by around 25%, 80% less stays in rehab and a 98% reduction in children misusing compared to patients using sublingual buprenorphine. The study must have been pretty detailed, because I initially couldn't understand why the reduction in children accidentally ingesting had not been reduced by 100%, but they must be factoring in that some patients will require "rescue" sl buprenorphine at early stages.
"The objective of this analysis was to examine the societal impact of Probuphine when compared to sublingual buprenorphine in clinically stable adults," said Mike Frost, M.D., medical director, Eagleville Hospital. "The potential effects of the buprenorphine implant versus sublingual buprenorphine were modeled with clinical trial data and inputs drawn from the literature using a 5-state Markov model. The modeled results included a 24% reduction in drug-related deaths and an 80% reduction in rehabilitation services utilization. It also predicted a 98% reduction in accidental pediatric exposure to sublingual buprenorphine."
I wish Titan would do a piggyback press release of their own...
Great find, thanks for posting!
Each death from overdose is a tragedy, but if this story is true perhaps it will raise public awareness. Meanwhile, the FDA issues self-serving press releases while probuphine languishes in their custody.
http://www.nydailynews.com/entertainment/gossip/prince-treated-drug-overdose-days-death-article-1.2610568
Who's which stooge: Rubin=Moe, Beebe=Larry and Sunil is Curly?
Several presenters mentioned the expected release of buprenorphine implants placed under the skin. The makers of the six-month Probuphine implant are working with the Food and Drug Administration.
Nice to hear probuphine was getting mentioned outside of Beebe's presentation.
Thanks, I learned a lot through your post! And I agree with your analysis, Braeburn and Titan are so very cautious, that I don't see them going public with a superiority claim unless it had been blessed by the FDA in some form.
Thanks for the "digging."
After all the hubabaloo at the PDAC Ad Comm about how to measure efficacy (and who to exclude from the results, etc.) it was interesting Titan/Braeburn stuck to their guns and claimed superiority.
The study demonstrated pre-specified non-inferiority as well as superiority (p=0.034) of long-acting, subdermal buprenorphine implants compared to sublingual buprenorphine during 6 months’ treatment. The SL BPN group had a larger proportion of subjects with 1 or more severe treatment-emergent adverse events (p>0.05).
I'm not sure how this works, but I think the FDA has to bless all marketing claims. If they have got the FDA to agree to allow superiority claims in marketing, then that has to bode well.
Yes, perhaps that means the side effects portion of the labeling has been agreed upon? I've got to say it was more informative and better written than Titan's.
Braeburn's version of the press release...
"We are proud to be presenting the results of our pivotal trial at this prestigious gathering of addiction specialists. We are indebted to the investigators and patients suffering from opioid addiction who participated in this study," said Behshad Sheldon, president and CEO, Braeburn Pharmaceuticals. "We hope for a speedy conclusion to the FDA's review of these data and to bring a potentially valuable new medicine to patients."
AMEN!
http://www.prnewswire.com/news-releases/probuphine-phase-iii-data-presented-at-american-society-of-addiction-medicine-asam-annual-meeting-300252321.html
Wow, that is really tragic. How many lives could have been saved if they would have acted in 2011...or 2013 for that matter.
For some reason, I had it in my mind that the FDA would make their decision 6 weeks after the PDUFA extension. We are now 7 weeks after the original PDUFA date, and 6 weeks remaining...despite all their press releases, I'm not sensing much urgency from the FDA.
Fingers crossed that the FDA will see reason.
If probuphine can be approved as a "baseline" dosage (to use Braeburn's term), and doctors are allowed to prescribe supplemental buprenorphine as they see fit, then it could be used as a tool in the frontline and not just with stablized patients. If that's the case, it begins to look a lot more like a $500 million a year plus drug. The baseline probuphine implant would guaranty the patient could not get high...the motivation for most to stop taking their medication.
Yes, a patient might need additional sublingual buprenorphine, and yes there is a risk that the additional buprenorphine might be diverted to illicit use (i.e., sold by the patient on the street) or accidentally ingested. But it doesn't change the fact that, for the 8mg dosage included in probuphine, those risks don't exist, and so they have been incrementally lessened. Probuphine plus sublingual is less subject to abuse than all sublingual. That seems incontestible to me simply as a result of the fact there are fewer pills/films available and thus less buprenorphine available to physically divert.
Most of the knocks I've seen on probuphine come from analysts or posters saying "yeah it will be approved, but only on a limited basis." Braeburn apparently doesn't agree, because their NDA doesn't include the limitation that all those people seem to be assuming is a certainty. It will be interesting to see how this plays out.
I think they can always extend a PDUFA date (I believe its just a goal, not a requirement). This is all conjecture on my part, but if I'm right:
1. Both the FDA and Braeburn/Titan agree that probuphine can be prescribed to patients needing 8mg or less of buprenorphine and that the product labeling could include claims about preventing diversion, accidental pediatric exposure, etc. If the labeling had a "black box" saying probuphine could only be used for 8mg or less, I think it would be approved by now. Still a pretty good market, but not the one that Braeburn wants.
2. The FDA either: (a) wants the labeling for probuphine to strictly state it is only intended for patients needing 8mg or less (i.e., #1 above), or (b) wants the labeling not to include claims about preventing diversion, accidental exposure etc. because its contemplated that probuphine will be used in connection with pills that carry the risk of diversion, accidental exposure.
3. Braeburn may be sticking to their guns and saying: "We have an effective, non-inferior and safe way of administering 8mg of buprenorphine that deserves to be approved on that basis alone. We don't agree to labeling that limits the patient class to those requiring 8mg or less, because sublingual buprenorphine is readily available for those requiring more. And we should be able to make all the non-diversion, accidental exposure claims that are inherent with our product. The fact that our product may be used in connection with other products that have those risks doesn't make our product, in and ofi itself, any less safe or abuse deterrent."
Not sure how it would ultimately play out. Braeburn has pressures to get probuphine to market, but it may be worth "playing chicken" with the FDA by not agreeing to bad labeling. Worst case they probably get an "approvable" rejection letter (saying it would be approved with the appropriate labeling), and they could then appeal the decision. They have logic on their side, and the last thing the FDA wants is a bunch of bad press.
Personally, I think labeling that restricts prescriptions to those needing 8mg or less is just wrong and worth fighting over because of the huge market that would be lost. If the question is just whether you can make non-diversion or accidental exposure claims in marketing materials, then it becomes a tougher decision whether to fight it.
Hunch.
So the FDA asked for clarification on the REMS, Braeburn responded, and the FDA extended the PDUFA date. Sunil has said Braeburn and Titan are working with the FDA to “finalize the REMS and the product labeling.” The biggest REMS issue I noticed was removal of the implant, but now that we are 47 days over the original PDUFA date and I just don’t buy the extension is related to REMS. Going over the FDA briefing material submitted to the PDAC for the Ad Comm, I really think what is being wrestled over is product labeling.
According to the FDA briefing materials, “The labeling proposed by the Applicant [Braeburn] suggests that baseline sublingual buprenorphine dose is the only characteristic required.” In other words, Braeburn wants a label that states: this implant is an effective means of delivery 8mg on buprenorphine over six months. Period, end of story. If a patient needs more buprenorphine, then the physician would be entitled to prescribe him “supplemental” dosages.
Braeburn’s suggested product labeling creates a huge market. Essentially, anyone requiring 8mg or more of buprenorphine a day is included. Although addicts in early stages of recovery might need more, the additional dosage could be supplied sublingually (or as the FDA calls it, through “rescue medication”). Why wouldn’t a doctor prescribe an implant as a “failsafe” measure to ensure compliance for all patients, and just use supplemental sublingual buprenorphine to counteract affects of early stages of withdrawal (and gradually reduce the dosage as the addict weans off opioids)?
This is giving the FDA heartburn. As they wrote in their brief: “…if prescriptions for as-needed sublingual buprenorphine are anticipated to be a routine practice, how these prescriptions will impact the product’s ability to mitigate misuse, abuse, and accidental pediatric
exposure.” And…”if a certain amount of supplemental rescue buprenorphine is to be expected at some phase of treatment, should clinicians be advised to routinely prescribe a supply of “just-in-case” sublingual buprenorphine to patients receiving Probuphine?”
On a purely logical basis, the FDA gets it. Probuphine delivers a non-inferior dosage of 8mg of buprenorphine, and is entitled to be approved on that basis alone. But the FDA may not want to approve labeling that talks about mitigation of diversion, misuse, etc. if the patient class is not limited exclusively to those needing 8mg a day, because they same risk of diversion and misuse will exist for those patients using probuphine in combination with burprenorphine pills.
So, the FDA may wish to have labeling indicate probuphine can only be prescribed “on label” to patients needing 8mg, but again, logic gets in their way. If probuphine is an approved method of delivering 8mg of buprenorphine, then its approved, end of story. They can’t hamstring physicians by denying them the ability to prescribe probuphine in combination with oral therapy. There is no logical basis for it. But they can say to Braeburn "you can't market this as being abuse deterrent if it is going to be used in combination with pills that cause abuse."
So really this is coming down to a battle over marketing claims. And I’m very glad we have a former FDA commissioner on our side.
Time will tell. I fully realize that there are many out there who do not share our enthusiasm. A few may believe the FDA has one last CRL in its sleeve, but I think even more just can't get their arms around an implant. I mean, why have something foreign inserted into your body if you don't have to is the argument. And then there is the issue of whether insurance will cover it...why would they pay for a $2,000 implant when $3-$4 a day pills are available.
With opioid abuse, I think the thing critics are missing is that an addict's decision making is suspect to say the least. Someone seems fine one day, and a few hours later has succumbed to his addiction. Removing the element of personal choice will be highly attractive to anyone serious about ending their addiction.
Turks, I love your enthusiasm. At times, I’m embarrassed to admit how much optimism I have about Titan. The key things for me are:
1. This is our second go-round with the FDA, and although the Ad Comm was about as much fun as a root canal, it went way better than 2013. The FDA has admitted efficacy in writing. The trial design was approved by the FDA, and I think there is a greater than 90% chance of approval.
2. Once approved, it will be all about sales. Braeburn is spending a ton of money to certify 1,500 physicians to prescribe and insert probuphine. That includes nurse practioners, which will greatly expand the drug’s reach.
3. I just have this gut feeling that it will take off. Having dealt with addiction in my own life, I really do believe that, in their sober moments, all addicts will agree that recovery is a day by day process, and they can’t be trusted. I think this will be the first choice for those whom it is made available to.
4. $300 million in sales of probuphine equates to 75,000 patients per year at $2,000 per treatment. I think they will get to twice that number. At $250 million in sales, Titan would receive around $100 million in sales milestones in addition to the royalties.
5. Chronic pain is following shortly after approval, with a goal of approval by 2018. Probably only one or two rods per patient, so the cost per treatment would be $500 to $1,000. Much bigger market…let’s say they get to 250,000 (especially elderly not in nursing homes). That would equate to at least $250 million in sales.
6. Royalty percentage is based on calendar year sales. If they are over a certain dollar threshold, then all sales for that calendar year get the “low-twenties” royalty. With $550 million in sales and a 22% royalty rate, that’s $121 million just in royalties.
7 Parkinsons and T3. Let’s remember, these are not new molecular entities. Just proven drugs where titration/therapeutic window is an issue. The delivery system has already been proven with probuphine. All of the rescue med nonsense won’t be an issue, because the patients won’t be weaning off an opioid. These are easy lay-ups.
With probuphine cash in hand, Titan won’t be pressed to push for the upfront license fees with its partners, and can instead insist on a higher royalty (25-30%). Let’s say the cost of treatment are around the same for probuphine. 75,000 of 1,000,000 US parkinson’s patients=$300 million. 25% of that is $75 million. Let’s say T3 doubles that, as 15 million suffer from thyroid issues. 25% of $600 million is $150 million
So, five years down the line, this is a company that has a good chance of pulling in over $400 million a year in royalties. And I haven’t discussed sales outside the United States.