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Braeburn Gets A Thumbs Up Vote from Ad Comm
17-3, even without a REMS. The atmosphere sure has changed regarding Medication Assisted Treatment over at the FDA.
https://www.prnewswire.com/news-releases/braeburn-announces-fda-advisory-committee-recommends-approval-of-cam2038-buprenorphine-depot-for-the-treatment-of-opioid-use-disorder-300547779.html
In fairness, Indivior submitted a REMS plan with their NDA that includes a restricted distribution system and surveillance monitoring to prevent diversion. Braeburn didn't submit a REMS.
Earnings...
Hoping we hear something about an EU partner/submission of marketing application.
Not sure about probuphine sales. They said 90% of the $40,000 in 1Q sales decided to do the procedure again, so thats $36,000.
Went from $40k to $77k in sales from 1Q to 2Q with "steadily growing sales inquiries." I would think we break $200k all together.
...trying to avoid gag reflex when I remember how much trouble the FDA gave Titan on probuphine. Yeah, there's no bias in favor of big pharma.
HHS is Finalizing Its Approach for Evaluating MAT Expansion Efforts but Lacks Performance Measures with Targets and Implementation Timeframes
Interesting reading...
[b]Efforts by private health insurers. Officials from private health insurers reported that they are expanding access to MAT through outreach or training for providers and through the following three efforts:
• Eliminating the need for prior authorization to prescribe MAT medications. Officials from three insurers reported removing prior
authorization requirements for MAT medications, thereby making it
easier for patients to access needed MAT medications more readily,
rather than undergoing a waiting period for approval to receive the
medications. Other private health insurers told us that they continue to
require prior authorization, intended for safety reasons and to reduce
drug misuse, and officials from one insurer told us that they will allow
a patient to access a limited amount of MAT medications for a period
of 24 to 72 hours while making a determination about the appropriate
treatment services for the patient.
• Modifying health benefit coverage. Officials from one private health
insurance plan told us that the company is redesigning the benefit
coverage for methadone and has removed member copays. This
effort is intended to make MAT medications more affordable and allow
members who are not able to use buprenorphine to have an
alternative, such as methadone, that is not cost-prohibitive.
• Incentivizing providers and health insurance plan members to use
MAT. Officials from four private health insurance plans described
plans to offer incentives to providers or patients to use MAT. For
example, officials from three health plans stated that they are offering
alternative payment models or paying higher rates to providers that
offer MAT, and another private health insurer is offering incentives to
its members who are enrolled in behavioral health programs that
provide access to MAT.
http://www.gao.gov/assets/690/688047.pdf
Braeburn's Ad Comm on injectables is tommorrow. Haven't had a chance to fully review the FDA briefing memo, but it's pretty interesting they didn't submit a REMS and the FDA is asking for one...I wonder if that will be a cause for a delay in approval.
31% drop out rate in the study, which shows how difficult it is to keep addicts in treatment. 90% of probuphine patients from Q2 had their treatment continued, although granted they are all patients who had been stablized on bupe. Still, with the high drop out rate, I would be interested to know if the injectables are that much more successful than sublingual. From the study...
The number of patients and healthy volunteers exposed to CAM2038 and discontinued from any study in the clinical development program was 226 (31.0%). However, the number of participants who were reported as discontinued to an AE in the clinical development program was low [12 (1.6%) out of the 729 exposures]. Other listed reasons for discontinuation included physician decision (n=13), lack of efficacy (n=12), lost to follow-up (n=45), withdrawal by subject (n=87), and other (n=11). The AEs leading to discontinuation are currently under review.
https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM582592.pdf
I think this and ropinirole are the exit strategy. They will keep it themselves to be in a position to sell the all the rights along with the company.
T3
I was wrong about the size of the hypothyroidism market…but my error seems to help our analysis. I had said the market was $14 billion. Instead, 14 million people suffer from hypothyroidism (the addressable market).
Looking at Zacks analysis below from March of this year, it’s pretty clear this could be huge with just the US market alone (not even factoring in the EU, with a market just as large), even if you discount Zacks estimates as being overly optimistic.
Number Afflicted
In Western countries approximately 0.3 to 0.4% of the population have overt hypothyroidism. Subclinical hypothyroidism afflicts from 4.3 to 8.5% of the population. The disease is much more common in women than in men, approximately 4 to 5 times10 depending on the definition of the disease. Our model anticipates a population of 14 million hypothyroid sufferers in the United States. Approximately 16% of this number will require T3, either as combination therapy in conjunction with T4 (14%) or as T3 monotherapy (2%). Penetration of Titan s T3 implant is anticipated to start out slowly at 0.4% in the first year of commercialization and rise over 6% over the next several years. In the EU, we see the market as being about twice the size of the US market and assume that the addressable population remains steady at 16%. Penetration into the EU addressable market is expected to begin at 0.3% and rise to 2.2% over the next several years.
--From the terrific results described in the poster, the addressable market is now 100% of the 14 million US hypothyroid sufferers rather than 16%.
--So, at year one, 0.4% of the market would mean 56,000 people using T3 implants
--At maturity, 6.0% of the market would mean 840,000 people using T3 implants.
Pricing
We apply a similar approach for our pricing estimates for T3 as we do for Ropinirole, given that liothyronine is a well understood generic with sufficient supply and is not a controlled substance. Titan has the ability to develop an implant that can release a drug substance for anywhere from three months to twelve months or more. Due to the shorter trial time required to perform trials for a three month therapy, we anticipate four procedures per year for implantable T3. Again, using Braeburn s list for Probuphine of about $5,000 per implant and $10,000 per year, we assume that the revenue per procedure is $7,000 per year, after discounts are taken. We apply a discount to the T3 implant to reflect less complex distribution requirements since it is not a controlled substance and assume $6,000 for a year of treatment. With implants required every 3 months, this equates to $1,500 per procedure. Our estimates for pricing outside the United States call for a 2/3rds price reduction to $500 for four treatments in a year.
--At $6,000 a year, US revenue in year one (0.4% of market) would equal 56,000 x $6,000 = $336 million
--At maturity (6.0% of market) , US revenue would equal 840,000 x $6,000 = $5.05 billion.
They were supposed to have had their pre-IND meeting with the FDA in the third quarter on T3.
They will probably run the trials for three or six months to get approval more quickly...FDA would require a three year trial for a three year implant.
If successful, it makes probuphine's potential look like peanuts.
The clear implication of the poster (at least to me) is that T3 alone (which currently is about 15% of the hypothyroidism market) could be substituted for T4 (which is the other 85%) when used as an implant.
That's about a $14 billion market in the US alone.
T4 requires dosing two to three times a day orally. Who wouldn't use the implant when you get one implant for...two to three years? And you will lose weight and control your cholesterol?
Possibly, off label usage for weight loss or cholesterol issues?
A lot of new information in the poster....
"Therapeutic substitution of L-T3 for L-T4 has been evaluated in hypothyroid subjects in a blinded crossover study with a multiple daily dosing scheme, and comparison of L-T3 and L-T4 doses that produce equivalent steady-state thyroidstimulating hormone (TSH) levels additionally resulted in L-T3-mediated weight loss and positive changes to lipid profiles without appreciable side-effects (1,2). A sustained-release L-T3 formulation could avoid issues of noncompliance to multiple daily dosing regimens."
So, T3 has already been studied as a substitute for T4 in a separate study (not run by Titan), and resulted in weight loss and positive changes to cholesterol levels.
"In beagle dogs, which closely match implant-derived serum levels seen in humans, the initial peak release from 3 implants (Cmax = 221 ng/dL,Tmax = 6 hours) was about 1.7-times that of the Css (128 ng/dL), which was sustained from 12 hours post-implantation through Month 8. Residual content analysis of implants removed on post-implantation Day 217 indicated that an average of 21% of the original L-T3 content was released. Assuming similar release characteristics in humans, 1 implant (227 mg L-T3/implant, 3 x 26 mm) will release the equivalent of ~25 mcg oral L-T3/day for >3 years following a single treatment."
Am I reading this right? A THREE YEAR implant???
"Serum samples taken before and after implant removal from dogs on Day 217 were also assayed for LDL, HDL and triglycerides levels. LDL levels went up from 4 mg/dL to 7 mg/dL, peaking at 48 hours post-implant removal. Triglycerides levels also rose from 31 mg/dL to 54 mg/dL, peaking at 12 hours post-implant removal (inset), and HDL levels dropped from 131 mg/dL to 118 mg/dL, with a trough at 24 hours post-removal (inset)."
So following removal of the Titan's implant, HDL (the “good cholesterol” decreased) and LDL and triglycerides (the “bad cholesterol”) increased, consistent with the findings in other studies.
T3 (Hypothyroidism) Poster is available
https://d1io3yog0oux5.cloudfront.net/_ea839ea383715833d75df26299b4b7c6/titanpharm/db/341/1198/pdf/T3+ATA+2017+Poster+42x84+101617.pdf
Forget Trump’s ‘public health emergency.’ Real action on the opioid crisis is coming from the FDA.
Titan's nemesis now turned savior? Gotta like this Gotlieb guy as FDA commissioner.
https://www.washingtonpost.com/blogs/post-partisan/wp/2017/10/26/forget-trumps-public-health-emergency-real-action-on-the-opioid-crisis-is-coming-from-the-fda/?utm_term=.2e69985a7495
https://www.statnews.com/2017/10/25/fda-gottlieb-opioids-medication/
https://www.vox.com/policy-and-politics/2017/10/25/16545302/fda-gottlieb-mat-opioid-epidemic
Christie this morning.
Seems confident money will be coming...
http://www.msnbc.com/morning-joe/watch/christie-on-opioid-crisis-we-have-a-9-11-every-2-5-weeks-1082716739752
Trump opioid declaration falls short, say state officials
So, the net effect of the declaration today is that states can access the Department of Health and Human Services Emergency Fund to fight the opioid epidemic.
That fund has $57,000 in it.
Not a typo.
http://www.politico.com/story/2017/10/26/trump-administration-to-declare-opioid-crisis-a-public-health-emergency-244200
In case you keeping score, $36.4 billion for wildfire/hurricane relief. Let's see if a single cent is offered for the opioid epidemic in today's announcement.
http://www.politico.com/story/2017/10/24/congress-disaster-aid-hurricane-relief-244125
The Opioid Epidemic is not a "National Emergency."
It's a public health crisis.
Thanks Mr. President.
http://www.cnn.com/2017/10/26/politics/donald-trump-opioid-epidemic/index.html
Registering warrants granted along with the loan transaction earlier this year.
Just dreaming...and not that they are in danger of doing something that makes sense in Washington, but what if, out of that $4.5 billion a year for the next ten years, they spend $1 billion and bought out the rights to probuphine. Believe me, Braeburn would sell.
Probuphine could then be sold at cost. $600 for four implants (stated cost in Braeburn's S-1 Registration Statement), plus say $200 for distribution, etc. $800 for six months treatment (cheaper than suboxone).
Braeburn and Titan could split the cash per the license agreement. Titan would get its $165 million in milestones, plus 20% or so of the $835 million remaining (call it $167 million) for a final split of $332 million to TTNP and $668 million to Braeburn.
That would be interesting to dig into. I noticed that "66% of patients completed the study." That seems like a pretty high drop out rate for a 12 week study. Presumably, one of three dropped out to keep using by either not taking their oral suboxone or not showing up for their Vivitrol shot.
I realize probuphine is not the answer in all cases, but you don't have that "not showing up" problem with an implant.
Opioid emergency declaration is supposed to happen tomorrow. Democrats just introduced new legislation today...$45 billion over ten years. There are enough republican votes to pass it in the Senate (with Portman/Ohio, Collins/Maine and Caputo/West Virginia voting with 48 Democrats), but not sure about the house.
https://www.baldwin.senate.gov/press-releases/legislation-to-address-opioid-crisis
FDA’s Gottlieb calls for greater use of medication-assisted treatment to fight opioid epidemic
Only took 15 years or so, but who's counting.
https://www.washingtonpost.com/news/to-your-health/wp/2017/10/25/fdas-gottlieb-calls-for-greater-use-of-medication-assisted-treatment-to-fight-opioid-epidemic/?utm_term=.ef2f26199682
Meanwhile, at least Braeburn keeps on training folks.
http://www.thenpa.org/events/EventDetails.aspx?id=1006617
Trump is at risk of blowing it on opioids, a member of his own commission warns
...or depressing
https://www.washingtonpost.com/blogs/plum-line/wp/2017/10/23/trump-is-at-risk-of-blowing-it-on-opioids-a-member-of-his-own-commission-warns/?utm_term=.b6004aad0db4
Scoop: Trump enlists family, Cabinet, Congress in opioid response
This will be interesting...
https://www.axios.com/trump-to-declare-opioid-crisis-a-national-public-health-emergency-2500127123.html
The Trump administration this week will make its official declaration of the opioid crisis as a national public health emergency, and President Trump will speak Thursday on combating the epidemic.
The big news: Trump will sign an executive document directing Cabinet agencies to take actions addressing the crisis, a top administration official tells us.
More details:
We're told this will be an administration-wide effort that includes Melania Trump, who last month held a White House roundtable on opioid abuse. Ivanka Trump has also spoken on the subject.
The administration is working on a massive advertising and public-
relations campaign to reach Americans.
Congress will be involved because there will be requests for funds. The administration response has been questioned on Capitol Hill.
Why it matters: The New Yorker's Margaret Talbot — who wrote a memorable piece about heroin in West Virginia, "The Addicts Next Door" — writes in this week's issue that Trump's upcoming moves are "a welcome, but belated, response to a problem that has been growing inexorably for nearly two decades."
"For all the coverage the opioid epidemic has received, the reaction to it has been consistently muted. No group of activists quite as angry and eloquent as ACT UP has emerged to make the crisis an urgent priority."
Opioids kill more than 50,000 Americans a year, 10,000 more than AIDS did at the peak of that epidemic.
"Something about the nature of this epidemic delayed the sense of calamity. As the coroner of Montgomery County, Ohio, has said, it's a 'mass-casualty event,' but one played out in slow motion."
Be smart: The opioid crisis has hit hard in Trump country — rural areas, and economically depressed white communities. For Washington, it's been out of sight, out of mind for too long — and a reminder of the blinders we have in the bubbles, which also delayed recognition of Trump's heartland strength.
At White House opioid commission meeting, insurance industry gets a scolding
https://www.statnews.com/2017/10/20/opioids-commission-insurance/
Hypothyroidism by far is TTNP's largest potential market...from Zack's March report:
Number Afflicted
In Western countries approximately 0.3 to 0.4% of the population have overt hypothyroidism. Subclinical hypothyroidism afflicts from 4.3 to 8.5% of the population.9 The disease is much more common in women than in men, approximately 4 to 5 times depending on the definition of the disease. Our model anticipates a population of 14 million hypothyroid sufferers in the United States. Approximately 16% of this number will require T3, either as combination therapy in conjunction with T4 (14%) or as T3 monotherapy (2%). Penetration of Titan s T3 implant is anticipated to start out slowly at 0.4% in the first year of commercialization and rise over 6% over the next several years. In the EU, we see the market as being about twice the size of the US market and assume that the addressable population remains steady at 16%. Penetration into the EU addressable market is expected to begin at 0.3% and rise to 2.2% over the next several years.
Pricing
We apply a similar approach for our pricing estimates for T3 as we do for Ropinirole, given that liothyronine is a well understood generic with sufficient supply and is not a controlled substance. Titan has the ability to develop an implant that can release a drug substance for anywhere from three months to twelve months or more. Due to the
shorter trial time required to perform trials for a three month therapy, we anticipate four procedures per year for implantable T3. Again, using Braeburn s list for Probuphine of about $5,000 per implant and $10,000 per year, we assume that the revenue per procedure is $7,000 per year, after discounts are taken. We apply a discount to the T3 implant to reflect less complex distribution requirements since it is not a controlled substance and assume $6,000 for a year of treatment. With implants required every 3 months, this equates to $1,500 per procedure. Our estimates for pricing outside the United States call for a 2/3rds price reduction to $500 for four treatments in a year.
It will be interesting to see if sales took a bump up this quarter.
Thanks Truth! Great News
So apparently someone running a rehab center without MAT has a friend at the OC Register...
Long-acting medications for opioid addiction help patients control their future, unreliable selves
How are people just realizing this...
https://www.statnews.com/2017/10/19/opioids-addiction-long-acting-medications/
Yes, he's very positive on Titan, but I think he's playing it a little cautious now given he was just as surprised as the rest of us with the lack of sales following launch.
It depends on whether Trump follows what the Commission recommends in its report. Now that Tom "MAT is using a drug to fight a drug" Price is gone, I think chances are he will.
The interim report highlights the early conclusions.
https://www.whitehouse.gov/sites/whitehouse.gov/files/ondcp/commission-interim-report.pdf
My favorite parts:
Immediately Establish and Fund a Federal Incentive to Enhance Access to Medication Assisted Treatment. Speaks for itself…the Senate almost approved a $45 billion over ten year fund as part of the healthcare legislation.
Require that all modes of MAT are offered at every licensed MAT facility, and that those decisions are based on what is best for the patient. Right now, the Vivitrol doctors only sell Vivitrol, and the Suboxone doctors only sell Suboxone, etc. This would require all potential modes of MAT to be offered to each patient, allowing for a customized recovery plan. Probuphine is good, but it’s not for everyone. Same for Vivitrol and Suboxone (and the injectables when they are approved). This should increase awareness of probuphine and help with sales (remember, they are only shooting for 2-5% of the market).
Enforcing the Mental Health Parity and Addiction Equity Act: Basically, requiring insurers to follow the law, which states they cannot impose less favorable benefits for mental health/addiction diagnoses vs. physical health diagnoses. If a doctor diagnoses someone as having a life threatening physical health condition (e.g., anneursym, heart attack, late stage cancer), they don’t have to wait for weeks for prior authorization from an insurance company before they treat the patient. Not so with addiction, and so changing that practice should make sales of probuphine grow.
National emergency declaration to come (finally) next week...
https://www.usatoday.com/story/news/politics/2017/10/17/trump-says-hell-declare-opioid-crisis-national-emergency-heres-what-could-mean/733391001/
I would think the most attractive things about TTNP to a Pharma buyer would be T3 and Parkinsons. The buyer could own the rights to those drugs and deliver (sell) it themselves. Malaria as well potentially.
Probuphine, the kappa opioid agonist and the mu receptor antagonist are all collaberations that will hopefully involve a nice income stream, buy nobody wants to just buy royalties.
Not sure about Type 2 Diabetes...they haven't said anything about a partner, but I assume there is someone in the background waiting the results of the feasibility study.
I don't see any conflict. Business is business. Braeburn licensed injectables from Camrus after all, which could be seen to compete with probuphine.
For indivior, there isn't a conflict either. They have no six month implant in the US, and there isn't any planned. So why not try to make some money on one in the EU?
It's interesting that Indivior characterizes its injectables as an "implant" because while liquid when injected, it quickly forms into a solid. I can see a marketing strategy where they promote the benefits of their one month and six month implants, verses Braeburn's implant which remains liquid but forms a shell around the surface, e.g., both implants can be removed in case of an emergency, and also there is no risk of dose dumping.
Probably whoever offers the best deal, provided they have an OK distribution channel.
Indivior would be ideal.
My guess is they will learn their lesson from the Braeburn experience, and pick someone that already has an established buprenorphine sales channel. Probably someone on this list.
https://www.pharmacompass.com/eu-ctd-dossier-marketing-authorisation/buprenorphine-hydrochloride
Thanks!