Member Info for Alquemie

Oooh, more fun with numbers!

More accurate to use point rather than lifetime prevalence, and being generous on peak uptake and discontinuation rates, Germany returns:

25.3m adult males, 14.5% prevalence of "bothersome" PE, 10% treatment seeking of which 70% end up on some form of pharmacotherapy = 257,000

15% peak uptake, 3 scripts per year, Euro 24 wholesale price, 15% net royalty= Euro 748,000 or approximately 0.5 Gibsons.

Extrapolating to the five core territories (average prevalence 12%, 87.4m adult males, other assumptions as above)= Euro 1.55m or approximately 1 Gibson.

Should roll out continue to the other urology franchise countries (which I still see as likely), I would not expect them to add more than 30% to revenue.

Ezzza, while I'm flattered and tempted by the free Octopus pass and new dog n' bone, I'm going to have to pass on this challenging opportunity.

Joking aside, while Mr Gibson makes an easy (and deserved) target, the RP board give the collective impression of a rabbit caught in the headlights. One would have thought that Jim "Related Party Transactions" Mellon, might have a number of decent pharma-savvy advisors, and more appropriate Board members, on speed deal, but, in Woodfordian fashion, either relies on intestinal intuition when it comes to biotech, or on the same bunch of not too bright mates sitting on the boards of his other enterprises.

All the more surprising given the range of issues facing RP: cashflow; the absence of licensable assets (no patent protection or know how) or progress on monetizing the data package through ex-European submissions (and initiation of bridging studies); reliance on a single underpowered study involving an untested PRO instrument for progression in the US; absence of commercial protection/market exclusivity in all territories other than the three year mandatory grant in the US some five or six years in the future; continued manufacturing issues with presumably no post-Brexit fallback in place.

Sounds grim, but still potentially addressable with enough funding, plus skills and expertise that RP cannot currently muster.

@Ezzza, your poster strategy did raise a smile, but as with most aspects of pharma marketing, it's not that simple.

In a nutshell, you can't promote a prescription product to the general public or even name the product unless it's within the context of an indication-specific "infomercial". Professional promotion is geared around clinical data and cannot make direct comparison or reference other products unless in the context of comparator study data. Even the provision of product samples is strictly controlled in quantity and duration, generally requiring a written request from a potential prescriber.

I don't buy into the notion that, after ten years of Priligy marketing, internet resources (healthcare sponsored, not the fake medicine merchants) and with Recordati investing in their own spiffy Fortacin national language websites, that lack of awareness of treatment options is an issue. The reams of published psychobabble on attitudes to PE indicate that simple embarrassment is only one of many factors.

Market development is rate-limited by the very low level of treatment-seeking and by the narrow prescriber base. Taking Germany as an example, Recordati has little primary care presence, but has an established presence in secondary care built around the Urorec franchise. There are close to 6,000 urologists and andrologists in Germany, although not all work in general urology or are accessible to sales reps, giving an initial target for promotion of around 3,000 prescribers. PE consultation is polarised, with some urologists seeing tens of patients per month, others next to none.

Treatment seeking is higher in Germany than other European countries, but is still only around 10% of men "bothered" by their PE: out of an adult male population of 25m plus, only around 250,000 are on any form of prescribed treatment for PE. Discontinuation rates are high for all treatments, so the available treatment population is static
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Recordati is doing what it can to reach urologists (reps, digital, conference workshop sponsorship, puff pieces in medical journals) but simple arithmetic dictates that it's going to be a long slow haul to gain traction and develop specialist prescriber experience. let alone diffusion of that experience into primary care. Menarini's experience suggests that direct to consumer advertising does little to increase treatment seeking.

So at current exchange rates and average wholesale price across Europe:

1 Gibson = 360,000 canisters (approximately). Or roughly the cost of the Phase II validation study, including data analysis.

New presentation available. Stated post CVC strategy is more or less as as before, perhaps more emphasis on expansion (both in breadth and geographically) of the higher margin rare disease franchise, growth through acquisition, less emphasis on consumer health (despite recent kicking of tires on various OTC assets).

Seems to be graphically slicker than in the past.

Still appear to be be soft pedalling on Reagila market potential. No mention of Fortacin in the product portfolio or pipeline.

http://www.recordati.com/resources/Pubblicazione/___b3bf0a046e1f4bbaa88bcf690363b40a_/presentation-august-2018.pdf

Not unusual in that this is a commercially sponsored sideshow, and allows more freedom over the use of product trade name than, say a conference presentation where you are usually restricted to referencing the generic name.

You also have more freedom over speaker selection. Herr Dr Prof Porst is on the Recordati payroll and is/was a consultant to Menarini (and a very enthusiastic advocate of dapoxetine).

All direct to prescriber promotion helps in the early stages, and as the core territory with the largest number of potential prescribers (urologists and andrologists), and treatment-seeking population (although still miniscule) it's critical that Fortacin gains traction in Germany.

Here you go, pages 71-72.

http://www.professionalabstracts.com/dgu2018/programme-dgu2018.pdf

Not much in the way of detail. Exercising my minimal grasp of German, I think it's titled something like "PE still a taboo subject".

A crumb of comfort for anyone wondering whether Recordati is having second thoughts regarding Fortacin, they are sponsoring a “minisatellite symposium” at the Germany Society for Urology conference at the end of the September.

A whole 90 minutes of PE related fun from assorted German cock docs and an infomercial slot with good old Prof Porst.

@MattD78, Fortacin was always intended as an add-in to the existing urology franchise and, as with Vitaros, I also expect it to be rolled out in the minor member states with urology sales forces- doesn't cost much to meet local blue box packaging requirements and cobble together local language collateral.

it's already barcoded in the Greek national formularly (will check the other countries when I get time) so all ready to go when and if they decide.

UK launch is wishful thinking (no sales presence or NHS endorsement- low presentation rates make for negligible private script volumes). I do have doubts about Turkey and Russia, in part because time and expense of securing marketing approval, but also the likelihood of a shift in geographic and business focus towards non-organic growth and higher margin opportunities. It's no secret that Recordati are looking at acquiring consumer and primary care assets being divested by large pharma, in part as a hedge against the expected decline in speciality sales.

@MattD78, HK approval requires real-time stability data (along with region appropriate accelerated stability data).

Real time stability data (18 months) for the 340l batch size will not be available until Q1 2019 (assuming the "impurities" issue is resolved), and it reads to me as if they've submitted 100l batch data. Providing there are no other shortcomings in the dossier, approval is certainly possible in 2018.

HK and Macau are not linked in any regulatory sense, but given their size, more realistic to sign up a single distributor serving both regions.

As to "sales traction", the rate-limiting step is not prescriber enthusiasm but the minute number of men who seek treatment (with a smaller number opting for pharmacotherapy). Recordati does of course have experience in pitching to prescribing urologists, but only a few will see more than a couple of PE patients each month.

PE treatment is mix and match, and by the time you accommodate concomitant ED and preferences for oral over topical medication, the available new patient pool is down to well under a third of new treatment seekers. Fortacin seems to me to have an obvious place as a second line treatment, but again, that's a pretty small patient pool.

So, while I would expect Fortacin to at least partly displace off-label topicals and find a niche in second-line treatment, arithmetic dictates a very long and shallow sales curve, and the underlying dynamics (first line use, repeat scripts and discontinuation rates) and potential peak sales (and time to peak) might not be obvious for another five years. I appreciate that sounds gloomy, but that's the nature of non-reimbursed sales in indications with low levels of treatment-seeking.

Recordati have talked about running a drug utilisation study, and a couple of decent sized post marketing comparator studies would do no harm. Whether they (or their new private equity owners) think it's worth the effort for what is after all only a franchise add-in is another question.

Certainly some interesting numbers......

The net revenue per unit is much lower than I expected: out of pocket cost obviously varies across the core territories, but once you adjust for national differences in distributor and pharmacy mark-up, net revenue looked to be around Euro 30-32 per unit. I suspect that the broadline wholesalers have taken this on at a very hefty discount, not surprising for a newly launched, non-reimbursed speciality product. Wholesaler discount should reduce on better volume.

Early days, so I wouldn't read too much into the sales numbers, although, stating the obvious, sales are not issued scripts, and the actual number of treated punters might only be in the hundreds. Recordati promotion is what you would expect for a franchise add-on, and with the usual national constraints on advertising. A second English language puff piece was published last month.

There are clearly still issues around manufacture. The figures given for both the 100l and 340l batch sizes indicate appallingly low yields (of 65% and 74%, respectively) for such a simple process, and with a relatively hefty labour and QA/QC cost for such small batch sizes, transfer price must be high for a product comprising cheap as chips actives and components. That "impurities" are being reported post six-month stability is of more concern.

As of August 24th, Phase II study start date is stated as 31st August. Estimated PDUFA date is way too optimistic (by 2 to 3 years).

My recollection was that RP had stated that, when HK and Macau registration was first announced, they claimed to be working with a local distributor, although that might just be my failing memory.

Perhaps Arron Banks's lawyer has had a quiet word?

Hmmm......timeline is more than a wee bit optimistic.

Let's assume that pilot study recruitment goes to plan, submission to the FDA might be by end November 2019. There's no agreed timeframe for COA instrument review (the non-clinical review took well over a year), but pivotal recruitment could start in Q2 2020.

Lag might be longer if they postpone the cost and effort of pivotal study set up while waiting, with very squeaky bums,for the FDA go/no go decision.

Even with the wind behind it, study and NDA submission will not be complete before mid 2022 (just benchmark against the first US study of less than 300 couples, which was 24 months start to finish: my back of envelope statistics give a 300-400 couple pivotal study size).

Add in the 60 day pre-acceptance review, 10 month PDUFA and you are are looking at H1 2023 at very earliest.

Pomander, to be clear, I'm stating that there is nothing to prevent generic encroachment, but don't see this niche as attracting the attention of the larger generics players (in either the US or Europe, once exclusivity expires).

Since market entry would be at very low cost, it's not impossible that a branded generic from a speciality player might eventually pop up, although as Promescent, Pre-Boost and other physician-endorsed products have shown, you can access the professional prescriber channel with even cheaper to develop non-Rx monograph products.

I do wonder how much damage the appallingly low quality of presentation has done to potential partnering opportunities. "First impressions" is a cliche, but largely true when it comes to licensing and investment.

Pomander, that's just one of several non sequiturs that should have been hoiked from the RP presentations years ago.

It references an FDA preference, dating back some 20 years, that certain topical generic submissions be supported by clinical data. This position has long been superseded by FDA initiatives to expedite generic approvals though acceptance of non-clinical and bioequivalence data.

Moreover, how can the FDA set criteria for a future ANDA submission when no originator product submission has ever been made, let alone approved?

The majority of generic topicals brought to market in the last decade, which includes a multitude of lidocaine-prilocaine formulations, have been approved on bioequivalence alone (plasma level, absence of local irritation).

While there are no technical or legal barriers, generic competition may not necessarily arise. As in Europe, the narrowness of the PE prescriber niche, the need for (expensive) promotion, and the absence of reimbursement do not support the standard generic business model of large volume, modest margin or, in being the only supplier, owning a high margin monopoly.

Curious, the delay actually goes back to 2010 and the first US study (in partnership with Shionogi). The FDA would not accept that that the method used to measure changes in distress or "bother" caused by PE were valid. Shionogi subsequently abandoned filing for marketing approval.

PLE/RP has had to develop a patient questionnaire (the PEBEQ) for this purpose and first satisfy the FDA that it met certain non-clinical criteria and was suitable for validation in the clinic. The non-clinical part took years longer than PLE/RP estimated.

The pilot clinical study is not intended to assess the performance of PSD502 but to establish that the PEBEQ is the right tool to capture changes in PE reported by treated subjects. If the results satisfy the FDA, PLE/RP can roll into a larger pivotal study (300-400 couples) that might allow submission for marketing approval.

There is no patent protection for PSD502 in the US but the PEBEQ does constitute intellectual property. If clinically validated, any third-party wishing to use the PEBEQ in their own PE studies would need to license or otherwise rights from PLE/RP.

If PSD502 is approved, it will have three years of market exclusivity in the US (but only one year of data exclusivity). A generic product would need only demonstrate bioequivalence, so the PEBEQ provides no direct defence or extended commercial exclusivity.

Stealing from the late, great Mr Bowie: "News had just come over, we had five years left to cry in"

Timeline is what it is, but at least there is an identifiable start to the process. The major unknown is time required for post-pilot FDA review, might be much longer than the three months I've allowed. I'm assuming any new COA requirements can be addressed by the Phase III protocol.

Outside of HK/Macau, bridging study requirements make for a minimum three years to authorisation, China is still five years plus, even if all of the mooted changes in foreign data acceptance are written into statute.

I have wondered why no Australian submission has been made- process is less than 12 months from submission acceptance, EMA centralised submission data is recognised, as are UK manufacturing sites. Not a big market, and with no reimbursement or market protection, but easier to access than other Asia-Pac territories.

Phase II validation study registered July 6th (NCT03578783). Single US study site, recruiting 100 subjects (half on placebo treatment, half on PSD502). Recruitment to commence August 2018, estimated study completion October 2019.

If the outcome is sufficient to convince the FDA that the PEBEQ serves as an appropriate measure for support of a label claim, pivotal Phase III could kick off around April 2020, with NDA submission possible by April 2022, giving a PDUFA date in April 2023.

RP has a talent for making the simple obscure.

The work-up to the 12 dose (5ml) batches was at pilot scale- 100l. The convention for variation submission at commercial scale is a three-fold scale-up, hence the move to 300l once stability for the 5ml fill volume had been established, around March 2017. Current production is at 300l batch size. If only 50k cans at 300l is correct, that's a surprisingly low yield for such a simple process.

The scale-up to 380l (which is not a common size for off the shelf vessels- possibly a custom job?) is necessary to reduce the transfer price. Confirmatory specification data (probably 6 month stability) was available by March this year, negating the withholding clause (Euro 1m) in the restated agreement.

The 380l variation has still to be submitted, but, when granted, this will become the commercial batch size.

HK submissions require real time stability data (and extended accelerated stability data at higher temperature and relative humidity). If the submission is predicated on 380l batch data, and if six month data was available in March, full 18 month data will not become available until around February 2019, with HK registration possible a few months after.

Macau may have less exacting requirements with respect to real time stability.

Having met him (Mr Tayong,Company Secretary/Financial Controller ), I'm pretty sure the FTE count is just one.

Filing (Full Accounts) of 3rd July 2018 gives the 2017 and 2016 headcount as 1.

http://tinyurl.com/ydf94smo

Filing does not add anything that's not been already been disclosed by RP, although, irony of ironies, no one appears capable of spelling the word "strategic".