Member Info for Alquemie

"has fortacin been officially lunched in taiwan due september"? Well, sort of...

Not "lunched" but I'm sure that there were nibbles on offer at the "official" evening launch symposium (24th September), starring good old Dr "The Next Viagra" Wyllie (erroneously tagged as "inventor"), and hosted by the Taiwan Association Andrology.

But, in common with the Recordati territories, no stock available for pharmacy distribution. Not reimbursed, out of pocket cost £84 a pop (can't recollect whether retail pharmacy pricing is capped in Taiwan, so true cost may be higher).

OEP apparently struggling to contain its indifference.

And still no Chinese pivotal study registered as of end September.

Guessing here, but the PRO data will surely be presented in the context of an end-of-Phase 2 meeting, for discussion alongside the Phase 3 study design (and whether as a new indication, one or two pivotal studies are required), and other key issues (critically, satisfying the fixed-dose combination criteria).

The last release indicated that the internal statistical analysis and study report were done and dusted- it's not impossible that the delay is down to other elements of the meeting package. Rule of thumb is meeting takes place around 10 weeks months from submission, meeting minutes provided after 30 days.

New name, same old haplessness...

Always difficult to judge the degree of truth attached to any and all ERP/RPG/PLE communication, but taken at face value, the latest excuse for lack of supply (following API shortages, missing or incomplete DMFs etc) reinforces the already well known uselessness of PSNW, a chronically underinvested minnow. That Recordati have left production in PSNW's incapable hands underscores just how unimportant Fortacin is to them.

True, there have been MDI component shortages, but all resolved over a year ago. That PSNW lacks the wit to secure sufficient stock for even the cottage kitchen Fortacin production volumes speaks, well volumes, particularly when they have been familiar with the product since 2014. Lord knows how they are going to cope with the near-horizon phase-out of Norflurane, the Fortacin propellant/solvent.

Funnily enough, still no explanation for the close-to-expiry product withdrawal in Italy or the curtailing of the OTC pilot in Germany.

Having worked with Kevin and his mates, and seen a fair amount of their work in the context of investment and licensing support, they do a good job within the limits of primary healthcare research, but you are right to take the numbers with a large pinch of salt in the absence of detailed methodology. Might help to lay out the process:

First, the physician sample is not random, but will have been pre-screened with respect to practice size, years in practice, familiarity with PE, with perhaps a question on "how many PE patients do you see" or "do you consider PE treatable by pharmacotherapy"?

The chosen ones are presented with a "target product profile" which lays out the characteristics of the drug (easy enough for Fortacin since largely defined) and impressions collected. The next layer of questions is intended to capture prescriber response as degree of interest in the drug; intention to prescribe; as first or second-line Tx; attractions and disadvantages.

Pricing is used to further refine prescriber intent- for example, high out of pocket cost might have prescribers limit use to a subset of covered or employed patients, or confine to Tx refractory patients.

As with all market research, the danger lies in bias and sample size (the sample of 70 is less than 0.07% of community based GPs and non-hospital based urologists). Only around 3% of urologists (private practice and hospital-based) specialise in ED/sexual medicine.

The "Viagra" comparison is a nonsense, and I suspect a Gibsonism. There was essentially no ED market outside of a very small number of urologists treating prostate and post-op patients, so completely misleading to use this as some notion of baseline.

But then everyone misuses/misquotes primary research to their own ends (yeah, done it myself), and I've yet to come across a licensee or acquirer blinded by it (generalist investors, even the big boys, can be a bit more gullible).

Dougie, I would ignore the Fortacin fantasy numbers for the US (indeed, for all territories) and focus on the reality.

The acid test for any product is the market. Despite field force and country-specific promotion by an experienced pharma partner, Fortacin singularly failed to capture prescriber or punter attention, so much so that Recordati, uniquely, took the decision to move it to OTC status before any degree of familiarity had been developed in the Rx channel, in the hope of perhaps hitting €1m annual sales. That's if they ever sort out manufacture.

Fortacin's failure is not down to geography, but that it is a mediocre, low-tech, undifferentiated product in a not hugely popular format. A "bother" label and all the DTC promotion in the world is not going to change this. With no meaningful commercial protection in the US, no one is going to spaff millions on post-marketing studies just to have their lunch eaten by a generic entrant.

Bear in mind that the Fortacin concept was devised in the 90s, arising from the delusion that a PE treatment might stand on the shoulders of the developing ED market. The world has moved on. Ask yourself why none of the ED pioneers have ever bothered to evergreen their franchises, or that given the alleged size of the market and despite low technical hurdles, big pharma abandoned PE drug development over 15 years ago, or that dapoxetine, despite near global approval, never got a second round with the FDA?

A PE treatment market does exist in the US but revolves around OTC FDA monograph products, low-cost off label drug use and increasingly, online men's health focused companies offering physician consultation, prescribing and supply all for an average of $3 a dose.

Lastly, consider the quantum and structure of the existing RP agreements, and those of the few past PE treatment agreements- seriously, is there anything there that even hints at "blockbuster" potential?

Not available anywhere in Europe since pulled from Germany and Italy back in February. And as a "Pharmacy only" product, only available on consultation with an in-store qualified pharmacist (not a "shelf" product, although you can post advertising material and pharmacy availability).

The FDA does provide feedback on study design but size/planned enrolment is down to the sponsor's statistician and is largely dictated by "power"- the minimum number necessary to show a difference between the treatment and placebo groups. This would have been easy to calculate, since the probability of change in study measures was established by the Fortacin pivotal studies.

To repeat an earlier comment, it would have been remarkable not have seen a difference between treatment and placebo groups, but PRO validation hinges on qualitative differences between study groups which do not always align with quantitative endpoints. The actual number of subjects is lower than that used in the power calculation, and this may makes interpretation far more sensitive to outliers- for example, if a positive effect on bother was reported by several subjects in the placebo group, and to the overall distribution of responses in the treatment group.

As with all RPG releases (sorry, ERP), not enough detail to really know what the story is. And does no one ever proofread Gibson's work?

"P" value alone doesn't mean much unless you also know the sample size (and if completion was 92%, does that mean only 80 evaluable?). Not clear how they will present this. I'd assumed as a full package submission through the DCOA, but perhaps as a product-specific measure in a pre-Phase III meeting?).

Given Fortacin's history, it was never in doubt that there would a measurable difference across domains and between treatment, placebo and baseline, but with the primary outcome bar set so low, and the very small sample size relative to other PRO studies, I still think this is a coin toss with respect to FDA acceptance.

Dougie, the Phase II is not a measure of Fortacin efficacy as such, but to establish that the PEBQ questionnaire can accurately capture subjective perception of the degree to which individuals are bothered by PE and after treatment. You could validate the PEBQ with any old knob spray or PE treatment.

Let's lay out the risks: Fortacin gives some degree of perceived improvement, in most men, most of the time, and the study endpoint is set at a low bar. So, all good there. On the obverse, it's a very small (and under-enrolled) study, with a short treatment period (1 month). Former obviously squeezes statistical analysis and confounds result stratification, latter means only a small number of sexual encounters over baseline and no time for subjects to get familiar with application.

Historically, patient reported outcomes have taken very big numbers (usually with a consortium of interested companies involved) and years to achieve validation. The FDA is supportive of "patientcentric" outcomes, but there may simply not be enough in the full package (PEBQ non-clinical plus clincial validation) to make a call on this.

Binary outcome, can't help but feel odds are somewhat less than 50%. Options on failure would be a larger study, or plunge ahead in the hope that an FDA AdComm can be persuaded, although after a decade of FDA discussion, this would not end well.

RP press release in my inbox, trumpeting the name change and sporting a classic Gibsonism:

..."In addition, Fortacin™, our core treatment for PE is expected to benefit with the introduction of mainland China's Three Child Policy in May 2021. It is estimated that Fortacin™ will be launched in mainland China in 2023 and has the potential to help an initial target market of approximately 9 million patients in mainland China in its first year of launch."

Guess he's never read the label or missed the part about Fortacin being spermicidal.

Fertility: Fortacin may reduce the possibility of pregnancy. Therefore, patients hoping to achieve conception
should either avoid using Fortacin, or, if this medicine is essential to achieve penetration, should wash
the ***** as thoroughly as possible five minutes after Fortacin has been applied, but prior to intercourse.

Almost as funny as the part about DLI bringing "exceptional brand value". Some confusion with "DHL", methinks. Or even the Durham Light Infantry.

@The Italian- that's an accurate read. InSilico, as have several other companies with an initial focus on gerontology/longevity have long since moved off into mainstream drug development, although InSilico's valuation is based on return through software licensing, rather than their early-stage pipeline.

DLI was divested to "The **** Artists Formerly Known as RP" for lunch money for good reason- it has zero value to InSilico. Or indeed anyone. Researchers can access the most cited "ageing clock" (Horvath, and like the DLI offering, based on DNA methylation read) online for free. Needs real data and techies skills though, and far less fun that a free "guess your age" app.

Dougie, something that I railed against as a shareholder was the PLE/RPG puffery around Fortacin, so clumsy that not even the greenest of analysts, investors or prospects could not fail to recognise it for what it was. To my certain knowledge, this turned off at least one potential partner.

Prevalence is no indicator of the true market (another gripe: PLE/RPG cite lifetime prevalence estimates, not point prevalence, resulting in an overestimate of at least an order of magnitude). The level of treatment seeking and health system perception of treatment worth (both negligible for PE) dictate value, not some fantasy sufferer estimate. Recordati declined to undertake post-marketing studies to establish benefit as first-line treatment of choice, pointless now with the shift to OTC.

I take your point about noise from a US approval helping in other markets, but remember that we are talking about a product with different unestablished brand names (Fortacin and Senstend, or whatever), no supporting post-approval data and different market channels (OTC versus Rx). Five minutes in the popular press are not going to make a difference. And, to reference my previous post, US approval has zero value without someone in place able to make the best of the three scant years of market exclusivity (but might temporarily lift the share price).

As for "persistence", given RPG's shaky status, they are hardly going to dump an asset that they overvalued and overpaid for. I suspect that the lack of potential has long been recognised- a hand of 2 and a 7 rather than a straight. Fortacin certainly appears to have worked on Mr Mellon in that it has curbed his oft professed "tremendous excitement".

DLI has as much to do with medicine as I have with underwater camel racing. That's not to say there are no serious players in longevity research, but the smart ones have transmogrified into drug discovery companies focusing on age-related conditions, rather than targeting senescence per se. Funnily enough, not many are big on apps.

Genuinely pleased that copper looks like being, uh, a silver lining.

Dougie, sold out a long time ago (my one and only AIM investment- happy ending, luck rather than judgement). Still follow for the chuckles over the RPG alternate reality. For fun, let me give you Dr Alquemie's world view:

Fortacin failed its marketing test in the most developed PE market in the world , even with national promotion by a company with the last remaining urology field force in Europe. Uniquely, Recordati switched a product with no established brand from Rx to OTC status, underscoring how little potential they see. Fortacin has lost its one point of differentiation and protection from the rival knob sprays in that it occupied a prescriber channel. OTC in Europe is tough, with significant differences between national channels, marketing claim restrictions and pharmacy-negotiated pricing. True, Germany and the UK offer broader online reach, but this also generates pricing competition.

Assuming the constant manufacturing issues can be resolved, Recordati will be content for Fortacin to sit in its big bag of OTC bits and bobs doing an annual €1m or so. Investment is long written off and it's a racing certainty that the triggers for sales milestones will never be reached ( the RPG royalty drops to 3% or less within 7 years).

What of new markets? Treatment-seeking is next to zero in the US. New entrants (Romans, etc) offer self-treatment at under $3 a pop (with consultation). CMS does not reimburse lifestyle treatments, and they are top-tiered by other insurers, making for high out of pocket costs (double whammy for high deductible plans). Expensive de novo market development and no established brand or sales history to draw from. No patent protection beyond three years from approval and no technical barriers mean that, if modestly successful, generics will cut your legs off. As an aside, no patent protection has huge implications for any third-party deal structure (Kimble v. Marvel Entertainment. Bummer).

More probable that between the undercooked validation study and inability to fulfil the combination product rule, Senstend (FFS...) will never see a Yankee dawn.

Treatment seeking is even lower in Asia. Taiwan already saturated with Korean and Chinese knob sprays and traditional medicine self treatments. And yes, China is big but reaching and developing a market will be slow, even if telemedicine and distance prescribing supplements the very small number of specialist prescribers. Again, no patent protection, and branded generics could be knocked out over a long weekend. The deal terms and structure indicate low expectation.

DLI is the 21st century equivalent of an "I Speak Your Weight Machine". Early-stage ML/AI pharma assets change hands for tens of millions. DLI was palmed off for $4m. Between mates.

Miners and oilers not in my wheelhouse, but sincerely hope that copper keeps climbing for the sake of LTHs.

"Locked" not "locked in". Simply indicates that study data collation is complete and that everything required for analysis is in place and that no unintentional or unauthorised change outside of the clinical data management team.

Another masterful piece of doublespeak, although JG needs to remember that the Ministry of Truth's strength was in ensuring there were no existent copies of past pronouncements to contradict their alterations.

Change in the China study is down to the CRO having a better grasp of statistics than RPG. Study size is now sensibly based on past outcomes and powered accordingly, and I'd bet on the design being 2:1 randomisation, 1 month baseline, 3 months on treatment, 1 month follow-up (but possibly no PRO or partner based endpoints necessary).

Funnily enough, no mention of product withdrawal by Recordati and halting of Rx and German OTC distribution. The various supply delays (and that scale-up has not been successfully achieved in over four years of trying) underscore the iffiness of the manufacturing process. As for "materials shortages", given the small quantities required (and that the length of time that PSNW have been tapped for clinical trial supply), this is simply rank incompetence or otherwise clumsy lie.

I'm pleased for Kevin and his mates at MME, with RPG still throwing handfuls of dinner money their way. Perhaps for another few bucks, they might help JG parse the information into something meaningful.

Six months seems a long time to top line results for what was a very small, single key endpoint PRO validation study. In fairness, we have a couple of clients using ex-UK based CROs (mainly in India) for data analysis which have suffered COVID related delays, but I do wonder whether not hitting the planned recruitment has precipitated a statistical analysis rethink. And last time I checked, the DCOA full package review timeline was 10 months, so don't get all unnecessary about near horizon news.

Doubleplus ungood.

The name change is a smart move- might confuse those big Aussie bailiffs when they pitch up. And the long queue of other recovery agents blocking the stairwell should slow them down a bit. Wow- a two-word brand name, although really a single word, I guess, with one being a synonym of the other. Clearly no beginning to the imagination applied, odds on it came from Gibson.

Given that the company is now so close to extinction that David Attenborough and Greta Thunberg are considering a campaign, perhaps "Black Rhino" or "Yangtze Finless Porpoise" may be more appropriate?

Nice to have clarity around Recordati's marketing intentions. I guess the "mentioning" was before they withdrew product from Italy and Germany. Bit of a shame about that €8m "clawback", Jamie…due February, wasn't it? No China payment yet, and none of the usual boiler plate regarding timelines- Chinese friends getting edgy about the manufacturing debacle and clinical trial supply? Not to mention Orient, who are awfully close mates with Recordati.

Perhaps such worries have been dispelled by the “tremendous excitement” (copyright Jim Mellon). of acquiring a sixth-form science project. Something of such translational importance that, drum roll and fanfare, you can use it to make a free app. Which can guess your age.... the times we live in, eh. Plus, horoscopes soon to be available on subscription.

I’ll genuinely miss Excrescence Languidly when it goes.

More than rumour- the AIFA recall notice of 24th February states "an out-of-specification result due to impurity during the stability studies".

What's important here is the lot expiry date- April 2021, which means a lot release of November 2019. The out of specification result is close to the granted shelf life of 18 months, meaning that, as in the early days of 12 dose canister development, stability cannot be extrapolated from 3, 6 or 12 month real-time stability measurements.

RPG 'fessed up to continuing supply problems in the 2020 interims, with PSNW on the naughty step. Let's suppose that, before end 2020, they made some further tweaks to sort out the stability problem. All good, but the AIFA recall indicates that the impurity issue may not rear it's head until close to product expiry, meaning that concordance with real time stability will not be established until Q1 2022 or later. I can't find a recall notice for Germany, disappearance so close to OTC launch may indicate caution on the part of Recordati should the German lot(s) also turn out to be out of spec.

So, even if this turns out to be a lot-specific issue, resolution of what might be a fundamental product flaw will take months.

JG once again being disingenuous with his "blame COVID" excuses- Long before the unwanted visitor from Wuhan, Recordati began scaling back its urology field force before H1 2019 due to Urorec loss of exclusivity. This, along with low Fortacin uptake, was likely the main driver for the shift to OTC.

Supply has been erratic since early 2019 (the "impurities" issue has been in the background since mid-2018), no UK availability since last June (with Docs4U desperately trying to flog an expiring lot at £1.99 a pop) or in most of the European territories. So, while there might have been little scope for new sales, manufacturing issues meant they couldn't even meet the dribble of repeat scripts. Simply astonishing that, with the latest fiasco of product recalls in Italy and Germany, RPG continues to shrug off the fundamental issue of product quality and consistency and its ramifications.

Apologies- looking at the lot expiry, this may not be the same batch as the withdrawn German OTC product, and that Fortacin withdrawal is down to the broader concern that product shelf life is under 18 months. Does not bode well that stability appears to be a continuing issue.

Fortacin now withdrawn in Italy due to impurity issue. Expiry date indicates that this was the batch released November 2019, which explains the recent withdrawal from Germany. And this after a market absence of well over a year through previous manufacturing issues, and with production still stuck at hand-knitted scale.
https://www.fanpage.it/attualita/farmaco-spray-per-disfunzione-sessuale-ritirato-dalle-farmacie-il-lotto-interessato/