FarmaZutical
5 years ago
I posted this on ShareCafe and thought Iâd share it here, too.
To reach 1500+ patients in the US, many will have to be diagnosed first.
There are app. 500 known EPP patients in the US today as far as I understand and I expect a swift uptake in most of
this population. Awareness will rise and more patients will probably be diagnosed over the coming years but I donât think
we can expect 1000 patients right off the bat. However, I think 6 implants are likely in the US.
UK has app. 350 known EPP patients and if NICE surrenders Iâm expecting around half of them to be
eligible for Scenesse during a managed access agreement unless the new PASS data gives us a better
QALY measure and full access. I think 3-4 implants will be maximum in rainy Britain.
My expectation is that we will reach 1000 patients treated in Europe soon.
NICE will have to accept the new efficacy data, and the Scandinavian countries
will follow. Denmark, Norway, Sweeden have app. EPP 100-150 eligible patients in total.
Germany will continue to grow and probably reach 500 patients treated soon.
Currently, only 4 patients are treated in Austria but the Ombudsman has requested
broader access so maybe we can get to 30-40 patients there, too. Switzerland and
Italy will also expand and The Netherlands are probably already maxed out. France is evaluating Scenesse for reimbursement as we speak. Spain could also
deliver 100+ patients. This is my short term base scenario for Europe. 1000+ patients at an average of
3 implants which results in US$45 m. revenues.
Add the 3-400 patients who I think we will be treating in the US within a year and we
have minimum 1300 patients of whom 300 will be getting up to 6 implants. Letâs assume the US patients will
be granted reimbursement for 5 implants in average and thatâs US$ 22 m. per year short term.
So my most conservative estimate is US$ 67 m. in revenues short term which would result in
US$ 25 pps with a 25 multiple which I find reasonable.
After FDA approval Clinuvel is de-risked and the rest of the pipeline should also begin to
get some option value. Today, I donât think Vitiligo, lotions, Enfance, XP or any
other aspect of Clinuvel than EPP in the EU or US is being given any value at all.
Australia and Japan as imminent targets for EPP should at least be given a risk weighed
value of something. Especially Japan is huge. When we are fully up and running in
Australia and Japan my EPP numbers double !
And if we move into one or two phase 3 trials for Vitiligo, the market will have to
begin seeing some value here, too. Vitiligo could be an enormous for the company and
even with 20 % risk weighted value being ascribed to Vitiligo today that ought to
add US$ 200 m. to our market cap. Imagine if we were a pre approval company with ONLY
Vitiligo but good results in Phase 2 and now moving into Phase 3. Such a company
could easily be trading at a market cap of 200 m. We have FDA approval for the drug
now so Vitiligo expectations has to begin adding some value, soon. And then there is the
rest of the pipeline.
My best estimate of fair value today is US$ 35 pps. which corresponds with
Sphene and Moelisâ 12 month targets of AU$ 50-58.
If all stars align and we get a move on, I think US$ 100 pps. is
possible within 2-3 years. When I dream, I see the company being acquired
at that stage at a 100 % premium which would give me an easy exit at US$ 200.
contrarian bull
5 years ago
FDA Approved!
Trading halt was until Friday or the announcement... not sure when trading will resume. I don't see anything on their web site yet.
===
FDA approves first treatment to increase pain-free light exposure in patients with a rare disorder
U.S. Food and Drug Administration (FDA) logo (PRNewsfoto/FDA)
NEWS PROVIDED BY
U.S. Food and Drug Administration
Oct 08, 2019, 13:00 ET
SILVER SPRING, Md., Oct. 8, 2019 /PRNewswire/ -- The U.S. Food and Drug Administration today approved Scenesse (afamelanotide) to increase pain-free light exposure in adult patients with a history of phototoxic reactions (damage to skin) from erythropoietic protoporphyria.
"For patients who are suffering from erythropoietic protoporphyria, a rare disorder, exposure to light may be extremely painful. Prior to today's approval, there were no FDA-approved treatments to help erythropoietic protoporphyria patients increase their light exposure," said Julie Beitz, M.D., director of FDA's Center for Drug Evaluation and Research Office of Drug Evaluation III. "Today's approval is one example of the FDA's ongoing commitment to encourage industry innovation of therapies to treat rare diseases, and work with drug developers to make promising new therapies available to patients as safely and efficiently as possible."
Erythropoietic protoporphyria is a rare disorder caused by mutations leading to impaired activity of ferrochelatase, an enzyme involved in heme production. Heme is an important component in hemoglobin, the oxygen carrying molecule in red blood cells. The decrease in ferrochelatase activity leads to an accumulation of protoporphyrin IX (PPIX) in the body. Light reaching the skin can react with PPIX causing intense skin pain and skin changes, such as redness and thickening. Scenesse (afamelanotide), a melanocortin-1 receptor (MC1-R) agonist, increases the production of eumelanin in the skin independent of exposure to sunlight or artificial light sources. It is an implant that is administered subcutaneously (inserted under the skin).
The efficacy of Scenesse was established in two parallel group clinical trials in patients with erythropoietic protoporphyria who received Scenesse or a placebo form of the implant subcutaneously every two months. The first clinical trial enrolled 93 subjects, of whom 48 received Scenesse, and were followed for 180 days. The primary endpoint was the total number of hours over 180 days spent in direct sunlight between 10 a.m. and 6 p.m. on days with no pain. The median total number of hours over 180 days spent in direct sunlight between 10 a.m. and 6 p.m. on days with no pain was 64 hours for patients receiving Scenesse and 41 hours for patients taking placebo.
The second clinical trial enrolled 74 patients, of whom 38 received Scenesse, and were followed for 270 days. The primary endpoint was the total number of hours over 270 days spent outdoors between 10 a.m. and 3 p.m. on days with no pain for which "most of the day" was spent in direct sunlight. The analysis did not include sun exposure on days patients reported spending time in a combination of both direct sunlight and shade. The median total number of hours over 270 days spent outdoors between 10 a.m. and 3 p.m. on days with no pain for which "most of the day" was spent in direct sunlight was six hours for patients receiving Scenesse and 0.75 hours for patients receiving placebo.
Scenesse's most common side effects are implant site reaction, nausea, oropharyngeal (part of the throat just behind the mouth, where the oral cavity starts) pain, cough, fatigue, skin hyperpigmentation, dizziness, melanocytic nevus (moles), respiratory tract infection, somnolence (feeling drowsy), non-acute porphyria (build-up of normally occurring molecules created during heme production) and skin irritation. Scenesse should be administered by a health care professional who is proficient in the subcutaneous implantation procedure and has completed the applicant-provided training. Scenesse may induce skin darkening, and a full body skin examination is recommended for patients twice a year. In addition, patients are encouraged to maintain sun protection measures during treatment with Scenesse to prevent phototoxic reactions related to erythropoietic protoporphyria.
The FDA granted this application Priority Review designation. Scenesse also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The approval of Scenesse was granted to Clinuvel.
FarmaZutical
5 years ago
From a recently published PhD thesis:
Clinuvel
In some ways, Clinuvel succeeded against the odds. Its initial focus was on a drug to promote artificial tanning. It was thwarted in that plan, but was able to pivot and refocus the drug on a niche drug therapeutic indication, called EPP. By 2014, this provided a pathway to an approval in Europe, yielding some early revenues through limited distribution to a handful of European treatment centres. Even with limited sales, because the drug sells for between âŹ56,000-84,600 per treatment course, it was able to generate $46 million in sales in 2018 and is projected to generate $133 million in 2019, based on a recent analyst report11. This continued sales growth, combined with the possibility of FDA approval in the US during 2019, puts Clinuvel in a strong position for future success.
Clinuvelâs drug, afamelanotide (Scenesse), is one of the few Australian-developed drugs ever to succeed in a Phase 3 trial, gain regulatory approval and generate sales. That alone is a mark of success. However, it is now also succeeding from an investor returns perspective. In September 2015, Clinuvel was trading under $3.00 per share. Three years later in September 2018, Clinuvel became the first Australian DDB to traverse $20 per share, breaking the $1 billion MV barrier. In a 2018 analyst report, it was predicted to reach a price of $31.70 per share in 2019, which would imply a valuation of $1.5 billion11. By April 2019, its market value was already approaching $1.2 billion and likely by the end of 2019, Clinuvel likely will be heralded as an unequivocal DDB success story.
Perhaps one of the reasons for Clinuvelâs success has been its leadership and culture. Dr Wolgen started as CEO in 2006 and implemented the strategic pivot that saw the company successfully pursue a niche therapeutic indication over the subsequent 10 years. In a 2009 âOpen Briefingâ interview (Clinuvel ASX release, April 16, 2009), Dr Wolgen stated: âThe key competency of my team is its resilience in professional adversities when encountered.â Finding ways to navigate
setbacks has certainly been a feature of Clinuvel over the years. In a recent article, Dr Wolgen reportedly described Clinuvelâs pathway to success as âtortuousâ12:
âRather than traversing along the fastest imaginable and plotted route to success, we have frequently been impelled to take tortuous avenues to achieve our objectives,â he told shareholders recently...Unlike the majority of ASX-listed drug plays, at least Clinuvel (ASX: CUV) has navigated these tortuous routes. It actually has a drug on market â to treat a rare skin intolerance to sunlight â which makes the company a rarity in itself.
The article went on to give Dr Wolgen much of the credit for the success of the firm. As an exercise, I calculated the IRR since 2006, when Dr Wolgen started; it was 10.6%. If Clinuvel achieves the projected $1.5 billion MV in 2019, that figure grows to 16%, which starts to approach a meritorious performance for a biotech firm.
In its 2015 annual report, Clinuvel declared the firm was making the transition to a âcommercialâ firm. However, Clinuvel is still a DDB and far from being a commercial-stage DDC. Based on the 2016-2018 annual reports, it was evident that the focus was still on R&D, with commercialisation limited to generating a low volume of direct sales to 44 EPP âexpert centresâ in Europe. Indeed, in its 2018 profit and loss statement, âbusiness marketing & listingâ, which was the only expense category that approximated commercialisation expenses, accounted for only 8% of the firmâs expenses, with the bulk of expenses associated with R&D and personnel.
Successful DDBs in the US have gone down the same path â using a niche market opportunity to generate early revenues to establish commercial proof-of-concept and make the product attractive to global commercial partners. While the EPP approval is a great regulatory breakthrough for Clinuvel and generates modest but useful sales, EPP is only one small indication for the drug. Its successful adoption by doctors for EPP will signal reduced risk as the company pursues much larger therapeutic opportunities in the future, such as vitiligo â the skin-whitening disease that affects up to 2% of the worldâs population and is a significant unmet medical need in the US, especially among African Americans.
What Clinuvel is currently doing with EPP is effectively a pilot-commercialisation program that is logistically manageable for a small firm with limited real pharmaceutical commercialisation capability. Going forward, that capability may be tested, especially once FDA approval is obtained. Nevertheless, in the short-term, it has allowed the company to deliver to the sceptical Australian market a âcommercialâ success story, even to the extent of posting a profit in 2018 and extracting a dividend to underscore the narrative. In terms of growing future shareholder value, it could be argued
that that dividend may have been better invested in more R&D to expand the future indications of the drug.
Over the next few years, as the indications grow for Scenesse, along with its potential launch in the US and the massive logistical challenge that represents, Clinuvel is going to need to rapidly expand its commercial capabilities. As noted in the 2018 analyst report: âTurning Clinuvel from a research driven company into a commercial global entity entails certain organizational risks, which could endanger the profitability of the company and therefore our price targetâ11.
The 2018 analyst report projected a dramatic growth in commercial costs from 2019, assuming a US approval. While it is feasible for a small Australian firm with no commercial experience or infrastructure to manage a handful of customers in Europe and without the help of a pharmaceutical partner or distributor, marketing in the US is a much more challenging proposition. Add to this, the potential expansion of the use of the drug beyond the extremely narrow condition of EPP to broader indications, and the challenge is amplified. As previously noted, infrastructure, management skills and culture are substantial barriers for a DDB seeking to migrate to a DDC. Life is much more complex at the commercial interface of the pharmaceutical industry and a large, multinational and highly-functional regulatory, logistical and marketing infrastructure is needed. Clinuvel may be able to make the transition to a DDC in the future, but to attempt it could represent a strategic âcommercial focusâ error and might even threaten the survival of the firm. If it succeeds, it will take many years and Clinuvel would become a rare DDC transition success outside the US. More likely, Clinuvel will realise the capabilities challenge in front of it and seek a global licensing partner to manage international commercialisation. It may even choose to be acquired by that partner, monetising a multi-billion valuation for its shareholders.
Fortunately, Clinuvel has found a way to avoid the Red Queen, despite its aging patent portfolio. The original patent on afamelanotide expires in the early 2020s, which is theoretically an insufficient ârunwayâ to attract a pharmaceutical partner. Moreover, because the drug is a small-molecule, it does not have the Red Queen immunity enjoyed by biologic drugs (see section 10.1.6). So far, Clinuvel has circumvented this problem by selling the product itself for EPP in Europe, rather than relying on a pharmaceutical partner. It has also filed a number of follow-on patents covering specific uses of the drug and its specific drug delivery system. The other commercial protection it has is that afamelanotide is not a simple pill that can be easily copied, but a drug delivery device that is implanted under the skin and slowly releases drug over time.
On top of that, EPP is also commercially-protected by its âorphan drugâ status in Europe and the US. This is another measure to avoid the patent Red Queen. In order to stimulate pharmaceutical industry development of drugs for rare (orphan) diseases, the US FDA and the equivalent authority in Europe (EMA) introduced orphan drug legislation, which gives post-approval commercial protection for a
drugâs use in a specific ârare disease. In the US, the orphan drug exclusivity is for seven years after approval, while in Europe, it is 10 years. This confers a relatively weak form of Red Queen immunity, because it is limited to the first approved indication of the drug.
Again, Clinuvelâs other patents and its delivery system may provide adequate protection for the other indications, but once a drug is approved in the US and starts to generate substantial sales, patents are typically challenged by competitors and such challenges are encouraged and rewarded by the FDA. While competitors will probably avoid EPP, because it is a very limited indication and is protected by orphan drug exclusivity, they will almost certainly challenge the use patent for vitiligo and if that patent falls, Clinuvelâs long-term value proposition may fall.
Regardless of these challenges, the Clinuvel experience doubtless could provide some valuable lessons for other DDB firms. That would require a detailed case study analysis, which is beyond the scope of the current research. However, it would be a worthwhile future research project.
Unfortunately, the Clinuvel story cannot be held up as an example of successful Australian science, as afamelanotide was not the product of Australian research. It was licensed from the University of Arizona (Hadley and Dorr, 2006).
Register for streaming realtime charts, analysis tools, and prices.
Jestiron
4 years ago
Monroe1
4 years ago
Cassius Longinus
5 years ago
Hot Features
Premium
