Member Info for Alquemie

Sales, at least to end 2018, are no great mystery.

RP declared royalties of Euro 120,000, being 15% of net sales (Euro 800,000). Average wholesale price is Euro 23.5 per canister, so that's a smidgen over 34,000 canisters from February through December 2018.

The unknown of course is how many Fortacin canisters are still taking up space in wholesalers'' warehouses, although, being a non-reimbursed product, Recordati is probably as much in the dark as anyone, but not something that's likely to keep its Board awake at nights.

With the adult male population of the five core territories being around 83.5 million (with, according to RP's play skool riffmatick, over 20 million men a weepin' and a wailin' over the demon PE), it's safe to say that wholesalers are not exactly caught up in the excitement. And this in the most developed market in the world for PE pharmacotherapy.

As to UK PR, why would you even bother? Fortacin is uniformly black or grey listed by NHS CCGs, with insufficient clinical evidence to change this collective decision, or otherwise make any impression on the minority of urologists in full time private practice.

Add in the Blue Guide limitations, and apart from largely useless infomercials, there's little you can do to get Joe Punter (or even Mrs Punter) kicking off their carpet slippers and racing to the GP.

I appreciate that the office junior has been really busy of late, what with the Financial Results release, Annual Report and all, but long past time that a designated grown-up was made responsible for checking his or her copy/paste efforts.

Too many chestnuts in this laugh-a-slide presentation to count, although it's astonishing that a year after launch, they can't even get the European out of pocket cost right.

I do wonder about the purpose of these "presentations"- some sort of corporate psychological reinforcement (does the fantasy become real if you set it down in PowerPoint), or perhaps a manifestation of the Dunning-Kruger effect?

Or is JG confusing "institutional investor" with "institutionalized investor"?

In all seriousness, does anyone with English as a first language ever proofread these reports?

Still the same howler regarding US submission timelines, although no reference to PRC and Taiwan timelines (I'd have expected feedback on the TFDA bridging study requirements by now, and as of three days ago, the HK MA has still to be transferred to OEP). And what ever happened to the all important scale-up from current cottage industry batch sizes?

Operations Update on p9 is not strictly accurate (Fortacin adverse events have been listed in the EudraVigilance database, although given how common Fortacin-related AEs are, it would be amazing if it was otherwise).

Reassuring that Recordati is so engaged that it's "considering" pilot (!) market research, only about two years too late to assist in launch planning (and after ducking out of a far more informative drug utilisation study). I don't expect Fortacin to get a mention at the 9th May analyst/investor presentation, but there might be more clarity around the future of the urology franchise, with the planned managed decline in Urorec sales.

Current exchange rate: 383,000 Fortacin canisters = 1 Gibson.

I wouldn't get overly excited.

Bunion's "recollection", (nice to know that he's still doing OK on his MMSE score) refers to the SimplyWall website, an Australian startup that uses autobot generated company profiles to drag in punters.

The "street" part is the .st domain name.....a small, but important detail and, granted, certainly enough to confuse the hard of thinking.

So much for the popular misconception that the internet is a more of a danger to young people....

Hmmm.... the Gibson time dilation effect still in operation....he really must stop relying on that five year desk diary gifted by the local noodle shop.

The China timeline may be not that far out if the existing acute tox and metabolite studies are deemed sufficient for Chinese subjects, although 18 months is pushing it for the mandatory clinical studies, so with review of the post approval adverse event/risk reporting plan, I'd say mid-2024 launch at earliest.

The US timeline is just a nonsense. If the Phase II read-out is Q1 2020 and sufficient for a Qualification Package submission, earliest FDA acceptance would be Q1/Q2 2021. Even assuming a single Phase III (and that may not be decided until the QP acceptance: two pivotal studies are generally required for a new indication), with a pre-NDA meeting and PDUFA pre-submission review, earliest launch is close to mid-2025 (safety and combination product issues not withstanding).

Not really... Jehovah's Witnesses bang on about life everlasting...

Musing on the lack of prescriber interest, the post-launch side effect profile has to be a concern, with irrationality, irritability, delusion and depression being all too common. And that's just in RP shareholders....

To end on a cheery note, while Recordati did not sponsor Fortacin-related industry sessions or housebroken KOLs at either the EUA or ESSM international congresses, local promotion is still ongoing, with Casen Recordati recently launching a Spanish PE awareness site, similar in content to the Italian, German and Portuguese sites.

Like the Beano Summer Special in days gone by (or any of Bunion’s posts), you can always count on a chuckle from RP releases. And this one does not disappoint. Was it really written by someone with English as a first language?

Hard to pick a winner, but loved the end of the last para on p2: “and it [Fortacin] will be rolled out in their other countries [sic] over the coming years, which is fantastic news”. Quite, back in 2014. Today, well, not so much. The expectation that they might see any part of the Euro 8m “clawback” or aggregate milestones from Recordati was another thigh-slapper. As is their trumpeting of “UK launch, or “making space for a pallet’s worth of stuff in the warehouse” as it’s known in the trade.

Quelle surprise! The DBC shareholding was worth next to nothing? Who woulda thunk it?

Riddle me this: revenue for the period is consistently stated as USD 6.235m, comprising signature payments to a total of USD 1.3m (USD 1m from Wanbang and USD 0.3m from OEP, respectively) and milestone and royalty payments.

Milestones and royalties from Recordati to end December are stated as Euro 4.12m or USD 4.72m, comprising Euro 4m launch milestones and Euro 0.12m royalty, in line with Recordati’s Fortacin revenue statement (Euro 0.8m).

Allowing for forex variation, there’s an extra USD 0.215m (Euro 0.19m) in the RP revenue total.

JG arithmetic at work? Or should we blame the office junior who drafted this bumper fun edition?

And, with under a million in the tank, Big Gary and Bazza from the Aussie Tax Office due to come knocking in three months time, and the next tranche of CRO payments due, looks like plenty of slapstick still to come between now and the interims.

I shouldn't worry about the tax bill. All covered. Just as long as Recordati flogs around 1.7m cans of Fortacin during the next three months.

Nice of JG to keep up the long established tradition of restatement of the US approval timeline. He finally seems to have twigged that review of a COA qualification package runs 8-10 months, although his estimate is still way out.

Pivotal study numbers will depend on how it needs to be powered to establish a significant difference in "bother", but at a bare minimum of 300 subjects (randomised 2:1, one month baseline, 12 week on treatment), you are looking at a 2 year minimum (just benchmark against the PLE/Shionogi sponsored studies). Numbers may need to be much bigger, or being a new indication, FDA may insist on two pivotal studies(there's a precedent for this in PE), taking submission out another 2 or more years.

With a huge caveat around first time COA acceptance and pivotal requirement, I'd place earliest possible approval end 2024, but anyone's guess until the COA response sometime in Q1 2021.

The timelines for change of MA in Hong Kong and for the IND/CTA submission in China are credible, standard NMPA review is 90 days, so not impossible that the milestone could be triggered early 2020 (approval in 2025?). I wonder why the TFDA submission and bridging study requirement are not mentioned?

And nice to see Recordati all fired up for further launches in the "next few years", and perhaps "looking" to roll out in Greece and Romania this year. So same as last year when the product was formulary listed, barcoded and priced up, then?

Sounds like "siamo molto entusiasti" has given way to "siamo molto indifferenti".

Looking forward to more comedy gold on Friday.

Yet another US men's health company ("Hims") offering distance prescribing for PE referenced in today's online Guardian.

Pricing around the same as I previously quoted for Roman's Health, at USD 34 for 5 setraline tablets, same for a rebranded monograph genital desensitiser product (lidocaine spray), or both for USD 63 including online prescribing fee.

Given that the out of pocket cost for consultation and prescribing is far lower than a doctor's office consultation (and that insurance may not cover PE consultation and treatment), it strikes me as possible that US distance prescribing companies might do far better than their European counterparts,

Obvious implications for Fortacin pricing in the US , which RP were touting at USD 20 per dose, if out of pocket costs with distance prescribing for established PE treatments are even lower than they are in Europe. Time for a rethink of the business model.

Less about competition from OTC products, although there may be reluctance to shell out Euro 40 or so if patient has tried a superficially identical Euro 5 knob spray in the past, than down to simple arithmetic.

Only a tiny minority of PE sufferers seek treatment and of these, only around two-thirds end up on some form of pharmacotherapy, with oral meds (dapoxetine, other SSRIs) dominating. With an available treatment pool of around 0.5 million men in the five core territories, even replacing all topical use with Fortacin would still only generate pocket money royalties. And while there's nothing wrong with Fortacin in the context of current PE treatments, it's not sufficiently differentiated enough to displace established oral therapies.

If ever approved in the US, Fortacin will need to compete with established OTC products (Promescent, Pre-Boost, etc) which are already promoted for professional use. On the other hand, there are new male health-orientated distance prescribing channels appearing in the US, which could make a low volume, price-constrained product like Fortacin viable. As a benchmark, a three-month supply of an off label SSRI is less than USD 60 delivered, while rebranded Pre-Boost benzocaine wipes are less than USD 3 each (as three month supply).

Sounds like you are looking in the wrong place.

Fortacin marketing is, rightly, devolved to national subsidiaries, and benefits from familiarity with national differences in ethical product promotion. The core territories (with the exception of France) maintain "infomercial" type local language websites. The Spanish and Portuguese medical prescriber collateral is particularly good. At launch, all five subsidiaries hosted KOL-led press conference which received some coverage in the specialist media.

The French and German subsidiaries both run Fortacin-flavoured promotions at national cock doc meetings last year. In short, decent, if unimaginative, first year marketing activity for a minor in-licensed product. Low cost, since they are using existing field force, with agency fees running to a couple of tens of thousand Euros and a monthly retainer being main expenditure.

Fortacin, along with Vitaros/Virirec, was licensed with the notion that sales might assist in defraying the inevitable decline in urology franchise earnings on expiry of Urorec exclusivity, or otherwise help squeeze the pips out by creating opportunities for additional prescriber facetime.

Virirec is only now hitting a tenth of projected sales and Fortacin is set to be equally underwhelming. Neither looks likely to warrant more than continued passive promotion, although with Recordati all set to introduce generic Urorec this year, the writing is on the wall for the urology franchise in developed markets.

As previously pointed out, net sales (to full line wholesalers or national subsidiaries) are not indicative of actual prescribing volumes.

That said, prelaunch and initial shipments were close to 21,000 canisters but only around 13,000 canisters in the second half of the year (at an averaged wholesale price of Euro 23.6), indicating that there's been next to no uplift in interest from wholesalers ( and, indirectly, from prescribers) from promotional activities.

Non-reimbursement always impacts on uptake, but on this showing, you can understand the indefinite postponement of further launches and reduction in active promotion. I don't see distance prescribing(in the UK and the few other core territories that permit this making a material difference, but remaining optimists might consider leaving off the sackcloth and ashes until the third full year of sales.

Just to clarify the significance of the Drug Utilization Study waiver, the CHMP initially considered this a necessary component of post-marketing risk assessment. The launch delay, limited marketing, and the practical difficulty in collating non-reimbursed product prescribing data have reduced the usefulness of the DUS in risk assessment, hence the waiver. Risk (as adverse event reports) will be reappraised at the next licensing renewal application (some four and a half years hence).

Ironically, had sales looked like they might justify the expenditure, the DUS would potentially have been very useful in optimising a re-vamped marketing campaign.

Not necessarily.....

Prilocaine (and lidocaine to a lesser extent) are broken down into metabolites with greater potential for causing methaemoglobinaemia and are also known carcinogens.

From the EPAR, PLE had to undertake a number of animal and volunteer studies to establish that even very high drug dosing did not result in worrisome levels of metabolites. The EMA was satisfied that, while there were unanswered questions around toxicity, product labelling and extended pharmacovigilance were deemed sufficient to reduce risk.

However, acute toxicity is not the same as chronic toxicity and very little data exists about the latter. Moreover, partner transfer raises a different set of toxicological (and ethical) questions.

There's danger in generalisation, but it's reasonable to state that the FDA are less pragmatic than the EMA when it comes to risk assessment. While the absolute risks presented by Fortacin may be vanishingly small, there is a real possibility that the FDA (and Chinese and Taiwanese counterparts) may not be immediately satisfied with the available toxicity data or the methodologies used in their generation.

Resolution, if required, might involve no more than the time and expense of additional metabolite level studies, particularly relating to partner transfer (it's worth flagging that teratogenic potential has not been resolved), although the FDA might also insist on submission of more extensive chronic toxicity data, and/or data from patient groups at higher risk of methaemoglobinaemia (through impaired liver function, age).

The true picture will not emerge until after the pre-NDA meeting (still years away) but even the most die-hard LTH should factor in that FDA approval, or even an NDA submission are not written in the stars.

As stated before, being non-reimbursed, it's not possible to access Fortacin prescribing data through national or subscription services (wholesalers may have a partial picture of use by volume and geography).

Falling back on indirect indicators, as of around end July, wholesale purchase was less than 21,000 units for five countries with a combined male population of 83 million (18-64) and is not suggestive of wholesaler enthusiasm (having skin in the game, wholesalers are understandably canny). The first year sales figure, while important, will not necessarily be indicative of trend: year 3 is the earliest on which to base projections.

Promotion, being devolved to national subsidiaries, has until lately been what I'd expect for a minor bolt-on product. Recordati did have a presence at two of the national cock doc meetings (Germany and France) last year, running Fortacin-focused presentations or workshops. Tellingly, they are not sponsoring any industry sessions or workshops at the ESSM conference this week.

What still strikes me as most strange is the decision not to launch in Romania and Greece despite being formularly listed (with agreed pricing) last August, and to "relaunch" is the UK, the toughest market in Europe, with distance prescribing being the only viable (low volume) channel.

The potential problems posed by Brexit might be part of the UK decision, but if as posted (by Bignose?) there are still manufacturing issues a year after initiation of commercial supply (still at cottage industry production level), then effectively parking a low volume, mediocre margin, non-core product does make commercial sense. And, speculation on Dr Alquemie's part, but with the fast approach of generic silodosin and changes in Recordati strategy and management, I can't help wondering whether the urology franchise is being wound down in developed markets.

Positive signs of interest would be even a limited direct marketing campaign aimed at UK secondary healthcare prescribers, an English language infomercial website, restoration of sponsored sessions at the larger Euro specialist meetings and publication of a couple of investigator-led post-marketing studies.

The 10% adverse event incidence is accurate, being the combined incidence of all treatment-associated AEs experienced by subjects included in the safety database (overall AEs: 9.6% in males, 6.6% in females).

While 10% may appear high, common AEs are self-limiting and easily resolved without consequence (just stop using the spray or try a lower dose) and unlikely to be of much concern to prescribers. The more cautious might limit duration of treatment due to the lack of chronic toxicity data ("Long-term benefits or harms are unknown", to cite the Drugs and Therapeutics Bulletin), or concerns relating to partner transfer.

The brake on prescribing enthusiasm is the paucity of clinical data, particularly the absence of direct comparison with established PE treatments. I'm aware that Recordati intended to undertake a post-launch drug utilisation study, but if uptake is as low as I suspect it is, this may now have been abandoned or postponed since useful information may take several years to accumulate.

By convention, an adverse event is "common" if the recorded frequency is less or equal to one in a hundred and less than one in ten. Greater than one in 10 is "very common".

MIMS is aimed at prescribers capable of considered interpretation of "commonly reported". Moreover, given the actives involved, the nature and frequency of adverse events is hardly unexpected nor worrisome.

Launched today according to MIMS online, likely be covered by other professional healthcare press.

Not that kind of hormone......

Old news, even by DM standards. Phase II study has been running since early 2017 . I've met with the company (Ixchelsis), ex Pfizer guys. The CMO is famous for running the Viagra clinical studies.

The drug candidate is an old Pfizer compound, originally evaluated in stress urinary incontinence, abandoned over a decade ago. Clinical efficacy to date in PE is in the same so-so range as dapoxetine, other SSRIs and Fortacin at a two to threefold improvement over placebo. Side effect profile is different to that of the SSRIs, largely benign and with very low risk of drug or alcohol interactions. Dosing is "as required", say one hour before the main event.

If the Phase II pans out, and they can secure funding or a partner, could potentially be approved in Europe by 2024. Like Fortacin, US approval is open-ended until an FDA acceptable endpoint is established.

Plus point is that it's an oral treatment but, as with current PE treatments, only modest efficacy, not curative and non-reimbursable, so will face the same hurdles of pricing, low adherence and very low levels of treatment-seeking. Like Fortacin, substantial post-marketing data will be needed to drive uptake.

But certainly a potential competitor in that it would offer another approved (first and second line) treatment option with likely broader appeal than topical therapy, although main impact would likely be displacement of dapoxetine.

Nothing "went wrong" with the FDA process other than PLE/RP underestimating the time required to satisfy the FDA requirement for definition of an acceptable subjective endpoint(s) and providing means of capturing and quantifying subjective data (the PEBEQ "bother" questionnaire).

The PEBEQ was not submitted for review until March 2016, with the FDA agreeing that it was suitable for clinical validation in August 2017, and the 100 subject pilot validation study kicking off in December 2018. The resulting data may or may not be sufficient for submission within a Full Qualification Package (a requirement under the revamped COA process, currently an 8 to 10 month review timeline). Pivotal study design will not be fixed until after a further FDA guidance meeting. PLE/RP have alluded to a single study, but as a new indication, the FDA may insist on two Phase III studies for NDA submission or a large single study. It's these unknowns which make JG's anticipated approval date sheer fantasy.

According to the October 2017 RP presentation, the combination drug rule still needs to be satisfied and it would be a rare NDA submission indeed if there were not a raft of other points that also require resolution.

The "barrier to generic entry" is a nonsense and references a pre-2000 FDA preference for supporting clinical data for topical generics, since superseded by broad acceptance of biomarker and other data. Of course, you never know the exact requirements until you have submitted an ANDA for review, but a lidocaine-prilocaine generic monograph has been in place for years (bioequivalence only required).

Patent term extension ("term restoration") is granted (at the discretion of the patent office, not drug regulators) as compensation for the time required for drug approval. No extension is possible given the gap between expiry and NDA submission (still sometime in the distant future).

The FDA does grant a period of market exclusivity which, for a product like PSD 502 containing generic actives, would run three years from approval (although data exclusivity runs only for one year).

Sloppy journalism indeed.

Having said that, seems strange to cite something as irrelevant and potentially misconstruable as the number of study doses- why not just say "in clinical trials involving almost 600 men [and their partners]?

But sloppiness in print is unfortunately the norm, with Bignose's post being a good example.

According to my diligence notes, Mr Gibson's bum hit the big chair January 1st 2014, with his appointment announced 30th November 2013, two days after Mr Openshaw's flounce/fall from grace/assisted exit.

Appointment of PSNW as the six dose canister "developer" was announced 26th March 2014 (with Mr Mellon providing a soundbite for the press). The Recordati agreement was announced 26th November 2014.

So, whatever Mr Openshaw's sins may have been, it would seem unfairly Orwellian to make him out as the Emmanuel Goldstein of the six dose fiasco. More a case of "The Two Jamies" than "The One Ronnie"....

All a bit sad when an old chap's powers of recollection start to go......voices in the head next?