Member Info for Alquemie

Pomander, no, and I never held much of grudge against him when I was a shareholder, other than over his painfully obvious lack of experience. History indicates that he's somewhat challenged in the communication and negotiation departments, but to be fair, there's no shortage of CEOs that share those deficiencies. And having managed several public and private biopharmas, I can empathise with the problems he faces in monetizing the PLE "assets" and in finding a facesaving way of deep sixing the DBC holding. Although he can always blame Mr Mellon for the latter.

Pomander, one can but envy his undoubted trousering abilities.

Pomander, while there is no beginning to JG�s talents, I�m sure that he leaves the clever stuff to others. Lord knows, the challenge of satisfying the FDA with respect to the PRO instrument, the combination rule and the inevitable gaps and inadequacies resulting from the age of the data package is daunting enough without the prospect of JG�s involvement.

Pomander, EMA and FDA have different criteria with respect to their respective consideration of fixed dose combinations. The EMA have only recently adopted guidelines along the same lines as the FDA. It could become a significant cause of delay either before or after NDA submission, but complex a problem as it is, PRO acceptance is the bigger mountain to climb.

Pomander, not a question of RP's competency (there are plenty of excellent regulatory consultants for hire) but the inherent difficulty in meeting combination product criteria. This is not the forum for expansive technical explanation, but the FDA will need to be convinced about the validity of surrogate measures and that the pharmacokinetic advantages justify both the inclusion of prilocaine and the relatively high total concentration of amide anaesthetics in the product. Ironically, satisfying the combination rule is much more involved than demonstrating overall product safety.

Pomander, I'm only going by what RP have presented with respect to the the US regulatory "to do" list. The need to satisfy the combination rule is cited as an issue for resolution in the last presentation (and in those going back a couple of years). It may have already been addressed but, as with progress on the PRO, this would surely have warranted at least a mention in an operational update. If the combination rule remains unsatisfied, RP could still proceed with a NDA submission without having an agreed product type classification although this carries obvious risk and the wiser course would be to undertake any necessary studies in parallel with the validation and pivotal studies. I've worked with a few companies which have successfully taken fixed dose combinations through both the NDA and 505(b)(2) routes to approval on the strength of monotherapy comparisons. This is clearly not possible for a eutectic product but the guidelines do leave scope for situations where factorial studies are not feasible. So, while not an impossible task, the nature of the product and the indication means that this is far from being a simple piece of box ticking.

At home, but I need to chair a West Coast telecon in half an hour,so very late wine o'clock tonight.Talking with at least two neuroscience specialists, so important that I don't slur or exhibit evidence of altered mood.... EMA view on safety was both appropriate and pragmatic, the FDA dwell far more on the "what if", often leading to the need to set up expensive studies just to prove absence of possible risk. The combination product issue must have been raised years ago, probably at or before the Type C pre-NDA meeting, so I'm surprised that it still does not appear to have been resolved, although there's always the possibility that RP have omitted to communicate an important tick on the checklist.

Pomander, you wrote "PRO 008" but I think you are right about RP referring to the study as PE-008 (my "SPA" is the FDA special protocol designation). Anyway, no biggie. RP timeline is based on an early 2017 start and has not been updated. Allowing for PRO clinical validation (8-10 months from study registration),then 4-6 six FDA months review and pivotal setup, 12-14 month to pivotal completion, 4-6 months submission preparation and 60 day pre-submission review, I make that a minimum of 28 months, call it a mid-2020 submission at earliest. The combination drug issue features in most of the RP presentations. Fortacin is unusual in that, while it contains two pharmaceutical actives, prilocaine essentially functions as an excipient. Since there's no evidence to establish its relative contribution to efficacy, and since inclusion raises additional safety issues (remote as they may be), the FDA may not be satisfied that being essential for formulation warrants the inclusion of prilocaine without additional safety data.

Pomander, I think you intended to write "SPA 008". And, assuming an early 2018 kick off for the PRO clinical validation phase, the "pivotal" part would not start until sometime in Q1 2019 at the earliest, making for a mid to late US 2020 submission. As to "missing information", it's obvious that even allowing for the more touchy-feely nature of PRO review by the COA office, 20 months is way too long to have gone without an actionable response from the FDA. The other, potentially more important, question is, with more recent guidelines on fixed dose combinations in place, have the FDA accepted the eutectic mixture argument as justification for the inclusion of prilocaine?

Pomander, good going, and just to fill in the gaps: Timm was divested to the late and unlamented Paul Capital as part of a debt equity settlement, then sold to Actient Pharmaceuticals, which was acquired by Auxilium, which in turn was acquired by Endo Pharmaceuticals in 2015, which immediately divested all of its speciality urology portfolio. Timm was acquired by management (I know the CEO and ex-CFO), relocated and still bumps along selling willy pumps, leveraging its historical VA and CMS connections (although much less of an earner since Congress discovered that Medicare were paying double the retail price). I'd missed the Preboost agreement, but makes good sense all round, giving Veru low cost and decent marketing reach through Timm's field force. OTC product, but US prescribers are allowed to endorse and recommend. Clinical data on Preboost is slim but it got good coverage at this year's AUA. Looks to be much of a muchness with other topicals, although it has a much lower concentration of anaesthetic than Fortacin or most OTC products, which might translate to lower side effects (over-numbing, partner transfer).

Hmmm....wasn't thinking about vodka until I read your post. Now trying to remember if there is any left at home. Could phone Mrs A to ask, but that has its dangers. Spent a fair amount of time in Poland and Zubrowka and apple juice was the usual, although, in good old British fashion, I passed on the apple juice, leaving more space in the glass for vodka.

My dear old grey haired mother once wisely advised me never to engage with those who mumble to themselves on public BBs. Wise advice, which I will ignore just this once. Shouty NIGELFOREST, your grasp of things clinical, regulatory or commercial reminds me of a drunk in a tent full of helium balloons. But, in the interests of enlightenment and that I enjoy a good chuckle myself, would you care to back your view on the supposed superiority of Fortacin? Short words,with not too many syllables would be fine. And preferably not lifted from an RP presentation (I'll be able to tell by the spelling mistakes).

Pomander, my comments were not specific to Promescent or any other particular PE treatment. The point is that all current Rx and OTC treatments are much of a muchness with respect to claimed objective improvement, with all being pretty "meh". Regulatory approval is not indicative of clinical superiority, but it does mean that Fortacin and Priligy can include "reduction in distress from PE" in their label claims which provides some level of differentiation from OTC products. I wasn't sure what you were referencing in the RP presentation, but if it's the "Competitive Market" table, I note that it still features the same mistakes and transpositions from when it first made an appearance two years ago (along with a host of still uncorrected nonsense). Attaching the appellation "lying bunch of fraudster" would be somewhat harsh, if not libellous, whereas " a collective with questionable communication and proof-reading skills" strikes me as a fair and reasonable description. The PE market is hardly formed and patient management is highly flexible, so there is clearly room for a new entrant. Something I've stated before but, in the absence of established or obvious clinical superiority, Fortacin can still find a niche as a second-line treatment (and first line for those with a dislike of regular pharmacy) and for those with acquired PE in the absence of obvious cause.

Pomander, Promescent is a monograph product so no clinical data was required for US marketing. US prescribers have a somewhat different relationship with OTC medications than their counterparts in Europe and elsewhere and while they can't prescribe", they do actively endorse and recommend OTC products, particularly where the out of pocket cost is less than the co-pay. This is the reason that physician-invented mongraph products like Promescent and Preboost are able to enter and occupy professional channels. There's no basis for the statement that Promescent is inferior to Fortacin, nor does the corollary hold true. Neither has been shown to be better, nor worse, than any other desensitising spray or gel. There is peer-reviewed published clinical study data for Promescent, but the study group has "self assessed" PE, with much higher baseline IELTs than the Fortacin study groups, so it's not possible to make a direct comparison. You can say that Fortacin is better than spritzing your little soldier with HFA alone, and, that, in clinical studies, the improvement is IELT is in the same ballpark as that achieved with dapoxetine, SSRI or lidocaine treatment. As an aside, the makers of Promescent have been unable to find a buyer (and took Reckitt Benckiser to court earlier this year, alleging theft of trade secrets). LLC, so difficult to verify, but using credit agency sources, I think revenues are sub $2m.

pxsmaaad, I'd take the figures and "analysis" in this report with a large pinch of salt. PE is largely treated off label (or self-managed) and it's not possible to quantify using script volumes or treatment codes or other industry standard methods. There is one specifically indicated drug, dapoxetine, but the main marketer, Menarin (and the beneficiary of the royalty stream, Royalty Pharma) are privately held and do not disclose revenues. A third party source estimates dapoxetine global sales as being around $70m in 2015, but this only represents a subset of PE treatment. Any numbers in the report, other than IMS or equivalent data for dapoxetine, will either be unverifiable developer estimates or prevalence model estimates. Most of the companies cited in the report abandoned PE drug development years ago, something indicative of the "quality" of the desk research

Douro reds are pretty tannic but old age softens them up. And "buying young" is sound advice for collecting good wines of any provenance. I club together with some old work mates and buy en primeur, the risk being that you end up with the odd mediocre vintage. As to not securing ROW licensees, I'd say that not having anything to licence has something to do with it. In the absence of patent protection and any ex-EMA marketing approval, the only asset is the wrinkly old EMA submission dossier, which may or may not be sufficient to obtain marketing authorisation in ex-European territories. A licensee would need to do the heavy lifting on MA preparation and submission with no guarantee of approval and, ex-US, with no market exclusivity as a sweetener. And if you are taking all the cost and risk, you don't frontload, nor get overly generous on backloading. And I'd want to own the MA in perpetuity. As with HK and Macau, RP could add value to the asset by sucking up the cost and effort (and risk) of securing regulatory approval to create licensing or distribution opportunities. The need to create a market in the absence of commercial protection certainly takes the shine of any licensing deal. Distribution is a possibility, but as a rule, distributors will not stump up for promotion or cover MA obligations (PV, risk management). Margins are pretty slender and a new product would probably involve a profit share. It might be slightly easier if Fortacin were an established brand, but that's all in the hands of Recordati. Even then, RP may not be able to use the trademark or exploit Recordati data or collateral to secure or promote within third party arrangement.

Aaah, Alantejo- home of the wine cork! More familiar with D�o (the "newer", less mouth puckering style reds) and of course the Douro but will now look out for Alantejo wines. There's certainly nothing "negative" about opting for a targeted launch, particularly as this is de novo market development within a narrow, specialist prescriber base. Unusually for a Rx product launch, there's no great time pressure and Recordati can focus on building prescriber awareness through their field force in parallel with directed (restricted registration) digital marketing. Sales development will be slow, but as a minor product acquired to preserve an ageing urology franchise, revenue, as with Virirec, will hardly bother Recordati as long as they consider Fortacin to have "legs".

Pomander, nothing to do with confidence or exclusivity, but sensibly making the best use of existing field resource and building in the most promising (and influential) territories first. As you say, anything relating to launch has been from RP, not directly from Recordati. There are certain operational "tells" available in the public domain which suggest to me a narrower but focused launch. I'll expand on this closer to March. Recordati have little to worry about from loss of exclusivity. Fortacin is not reimbursable and will remain promotion sensitive; generics companies rely on the certainty of national payers switching from originator products to effect cost-savings and do not undertake product marketing. A branded generic would need to compete directly with Fortacin within narrow prescriber channels and would require direct promotion. If there are worries on Recordati's part, they are more likely to centre on the lack of post-approval clinical data and pricing, although free pricing gives them the opportunity to balance uptake against margin as the market develops.

MattD78, Recordati are now the MAH. The six month period is simply to allow administrative transfer of responsibility for pharmacovigilance, risk management, safety updates and MA maintenance. RP remains responsible until these functions are transferred and the EMA notified. I'l stick with my March 1st press release prediction, and I'll repeat a prediction that I made a while ago that active promotion will initially be confined to Italy and/or Germany.

Pomander, it wasn't my first gin distillery visit but certainly the smallest I've been to. Have offered to buy some of the stock if business fails to take off. And I've been an ardent fan of Zubrowka for several years. Apologies if I did not make myself clear, but I meant that the Macau filing is most likely at the behest of the HK distributor that RP are working through, with the notion that a distributor of any size would have a presence in both HK and Macau and that there is little extra cost or effort entailed in making two submissions. The PLE/Invicorp connection is all in the public domain (the 2007 press release pops up if you use "Invicorp" as a search term). It's the only product in the world that contains the actives VIP ("vasoactive intestinal peptide") and phentolamine, both mentioned in the March 2017 presentation, so easy enough to identify the product without being "an insider". BDSM enthusiasts, aside, injected ED drugs are the last gasp option for those with totally wrecked endothelial function through poorly controlled diabetes and/or cardiovascular disease or nerve damage from prostate surgery. Non-injected alprostadil treatments (such a Vitaros/Virirec) are a more recent and less painful option. The "logic" appears to be that the actives in Invicorp can be combined and delivered in a spray, which, given the nature of the actives, their mode (and site) of action and that there is close to a 100-fold difference in their effective concentrations, might take more than a wee bit of effort to reduce to practice. I'm truly surprised that someone with an understanding of pharmacology and at least some grasp of the limits of topical delivery would ever present such whimsy.