Member Info for Alquemie

Pomander, apologies- I did not intend to confuse by presenting a multitude of factors that might contribute to the delay. In suo simplicissimo, no study registered=no subject dosed=no progress towards NDA submission. RP's timelines have been ever mutable, with the last "update" of October 2017, giving Q1 2018 as the anticipated Part I read out, and Q2 2019 for Part II read out, making for a current minimum delay of 15 months. Making the huge assumption that the revised COA and NDA submission requirements will result in no further delay in study registration (and my understanding is that FDA legacy qualification process has still to be defined), if study site sign up and screening started tomorrow, the earliest possible US approval remains over 40 months away.

Pomander, I listed a number of reasons, both regulatory and strategic. that might credibly account for delay. For whatever reason(s), no interventional study has been registered despite a Special Protocol Assessment being agreed with the FDA in December 2014. I don't believe that RP has been inactive, but simply guilty of underestimating the difficulties in meeting key pre-study requirements, a situation since compounded by the as yet to be defined amended COA and NDA submission requirements and possibly changes in the regulations governing fixed-dose combination products. You could try asking, but RP may genuinely have no idea as to the US timeline.

Pomander, apart from being somewhat forthright in your opinion of the FDA, I didn't think that there was anything in your post that merited its removal. It's a matter of record that RP have yet to register a pivotal study in the US or other jurisdiction. The reason(s) may be regulatory: that no robust PRO is in place, or that other Special Protocol Assesment requirements have not been met; that the absence of a defined transition process and the additional NDA requirements under the 21st Century Cures Act offer further hurdles, or that the available data package is otherwise insufficient to support an NDA submission. The reason(s) may be strategic: RP have insufficient resource to initiate and complete a pivotal study and meet the PDUFA fee, or are unwilling to risk initiating pivotal study until a marketing partner has been secured. Interventional study registration is a prerequisite for local ethical approval in any developed country and its existence, or absence, is easy to establish. I would start your search here: https://clinicaltrials.gov/ct2/home http://apps.who.int/trialsearch/Default.aspx Off topic, but I am curious as to why you think that the FDA might be biased by foreign ownership or that the approval requirements for Indian submissions (all through the ANDA process) might be somehow different: the number of FDA warning letters issued to Indian manufacturers suggests that familiarity has not led to reduced vigilance. True, a submission from a Chinese company might be subject to additional scrutiny, but that reflects the historical lack of harmonisation of the Chinese domestic regulatory process with that of other economies. Having said that, the FDA were happy enough to recently approve Trogarzo, a biologic HIV therapy manufactured in Shanghai.

Pomander, what makes you think that an NDA submission from an "Asian or Chinese" sponsor might be treated any differently? If RP ever get around to dosing a subject in a pivotal study,then it will be in the US: the existing dossier comprises ICH-compliant European and US data. Keeping Catalent as the US clinical trial supply manufacturer would mean that there's not even the complication of foreign manufacturing site inspection. Since around one third (300+) of all FDA approvals last year were from Indian sponsors, it's fair to say the FDA focus is on the quality of submission and of manufacture, not geography.

Pomander, there are such sweeping differences in treatment seeking, market access, channels, pricing and promotion, that I sincerely doubt that a regional licensor would be much influenced by European sales. Post-marketing clinical data might get some attention, but that's years away. The most obvious constraint is absence of approval outside of the EMA, meaning that a licensor would need to subsume the cost and risk of securing regional marketing approval. The current dossier is clearly inadequate for FDA submission, likewise for the Asean harmonization territories and China and, should marketing approval be secured on the back of additional clinical (and perhaps preclinical) data, a licensor has no benefit of patent protection or market exclusivity (bar the three year minimum in the US). RP don't even own the trademark, so the Fortacin brand has no value ex-Europe. All in all, hardly a compelling licensing opportunity, and a situation unlikely to change until RP put some solid effort into securing additional marketing approvals, even if only in minor territories and/or where there is less restriction around product label claims. Outside of Hong Kong, the only other relatively accessible markets that might accept the available dossier for marketing submission are Australia and NZ.

Pomander, it's more about data collection than sales volume per se. It's very difficult to get high resolution data for non-reimbursed Rx products, which is why Recordati are putting their own drug utilisation study in place. The rate and shape of ramp-up is very different from that of reimbursed products as there is no early stocking of inventory by national or regional healthcare system purchaser, nor restricted formularly to drive prescribing. Although an admittedly arbitrary measure, full 12 month data (post test marketing and initial sampling) will indicate where "true" sales sit, a figure critical to RP both with respect to the real life level of royalty income and an indicator of whether the clawback might be attainable. Historically, Recordati do not report individual product sales under 3% total revenue, so reasonable to say that any special mention of Fortacin is unlikely. And to repeat a point I've made before, given the size of the population under treatment, a small, largely secondary care prescriber base and the issues around all non-reimbursed Rx products, it could be three full years in the market before it's possible to judge whether sales might eventually hit even Recordati's expectations.

Being a devolved/staggered launch, there won't be sales data worth mentioning in time for the interims. Only just launched in Germany (healthcare/pharma journalist-oriented press conference end of last week and German website now up). Sampling/test marketing will go on for several months across the core territories. Pre-wholesaler/wholesaler figures will only be available up to end of July for inclusion in an August release. Recordati don't break down the small change (and Rx info providers like IMS don't routinely collate non-reimbursed product data), so first public indication of prescriber interest (with full 12 months of sales across the core countries) will be royalty income in the August 2019 interims.

No, it's accurate, unless they've gone on a hiring spree in the last fortnight, or were perhaps counting interim staff. Was it Romero you met at MI? Nice guy- quiet, but did not need prompting to get the beers in. My understanding is that the Oxford office is shared with, or sub-let from, an ex-contractor.

Pomander, I can answer your "support team" question with confidence- none, since the only PLE employee is the company secretary/financial controller (Mr Tayong, who I met through happenstance. Turns out we have a mutual friend.).

If the ex-core territory launches are true, roll-out is simply following the existing urology franchises. Value is more to do with creating the opportunity for face to face prescriber discussions (who must be pretty bored of silodosin pitches) as was the case for launching Vitaros in minor territories, than driving Fortacin sales. Another Fortacin website is now live......step forward Jaba Recordati. http://fortacin.pt/. Downloadable professional collateral looks very similar to that of Casen Recordati, but unlike the Italian website, there's no way for prescribers to register interest directly. Might still be a work in progress, although could be down to national differences in Rx product promotion regulations.

Pomander, be fair- I lumped together a response to two of your posts. I'd have thought the current lack of effort would be obvious even to those with no marketing experience, although I do have the advantage of being able to access subscription trade/prescriber-orientated channels and have yet to see a hint of a marketing campaign. Bonus points to anyone who can find a a public domain product listing or digital/print professional or consumer communication outside of Italy or Spain. Not sure why you are sensing "anger" (channelling Master Yoda?), but certainly bemusement at why Recordati is paying for warehousing (especially for a such a short shelf life product) well ahead of active marketing. Given the nature of the product and the market, I've always expected them to play the long game, but it does help if you actually get a toe to the ball. I'm not expecting it, but I'd genuinely like to see Recordati eventually bring some creative promotion to what is, by any standards a very tough market, with next to no treatment-seeking, few experienced prescribers, empirical pharmacotherapy selection, subjective definition of bother and improvement, no reimbursement, and no exploitable differentiation over low cost OTC products containing the same active. I have a good friend who has spent a lifetime in marketing. A good few years ago, he was approached to manage the re-launch of "Blue Nun", the favourite tipple of Alan Partridge. Easy peasy compared to the challenge presented by Fortacin.

Pomander, deal terms were commensurate with Recordati's sales expectation for a franchise add-in that might eventually bob along at somewhere north of Euro 10m a year, with decent odds that it might wash its face over the product life cycle. Chump change for an approved pharma product (less than Recordati paid for limited rights to Virirec, still only doing around a Euro 1m, and about the same paid for a couple of OTC laxatives, France only). And RP have stumped up all of the manufacturing costs. E5 is critical as it's the only credible near to mid-term source of revenue, well barring the HK/Macau megamarket in a year or so.... And the context was that it's borderline delusional to believe that near term sales revenues will be sufficient to get investors salivating. Launch responsibility has been devolved to the subsidiaries, with only Spain and Italy having even bothered to list, let alone invest in collateral. Lump together agency single country set up costs and a one year contract, medical writing, and a few KOL bungs and you are looking at less than the fully over-headed cost of a single sales rep. It's a few years back, but contrast Recordati's efforts with the Menarini dapoxetine relaunch. As to global potential, only relevant if you can realise it. US timeline is now open ended, with probably a whole new world of hurt arising from the Section 507 requirements, the CFDA reforms mean squat for generic active, non-patented protected foreign drug products, the Asean Harmonization countries all require local population bridging studies, S. American registration is years away. The absence of patent or other commercial protection and full exposure to the risk and costs of seeking market approval does not make for a compelling partnering case. I understand the LTH mood, but it's not as if any of these core problems have suddenly fallen out of the closet, only that RP have elected not to communicate or address them. Perhaps emailing a few pointed questions such as "when will the first subject be dosed in the 008 study " or "when will a MA submission be made in any major territory" might rattle the cage?

Bunion, I appreciate that you have no experience of pharma marketing, but even for a minor product launch, Recordati has clearly gone to no great expense. That aside, the prediction that six month and first whole year royalties will be pocket change is simple arithmetic, whether you apply a "golden" sales curve and work back from Euro 25m peak sales (admittedly a nonsensical methodology, since Fortacin is not reimbursed and will not benefit from national or regional healthcare purchase arrangements), or use a bottom-up estimate, even allowing very generous uptake in the PE treatment population. No big deal for Recordati since they've paid buttons to own Fortacin and can afford to wait for the outcome of the drug utilisation study and rep feedback. And, while I'm surprised that (so far) they have done little on prescriber education across the core markets, I view Recordati's approach as pedestrian rather than "dumb". As for "dumbing down" RP, they seem to be doing a bang-up job without my modest contribution

Bunion, by the time the various Recordati subsidiaries eventually complete pre-marketing and test marketing (on which no royalty is payable), and receive net sales figures from the various broad-line wholesellers, RP will be lucky to have received a couple of months' worth of royalties before the next interims go out. Might be enough to cover a round of noodles and ice creams, but it's hardly going to galvanise new or existing investors. Being a sensible sort of chap, I'm sure that you are buying and holding like a good 'un. Plenty of hot action on the horizon in HK for healthcare inclined institutional and private investors, with the likes of Adagene and Hua Medicine topping off from recent private rounds in preparation for HK listings.

On the other hand, savvy Chinese investors, or indeed those of any other ethnic origin, might want to wait for a hint of sales. There�s certainly no tearing hurry to go throwing yuan around. While I've never expected fireworks, the Fortacin launch remains surprisingly lacklustre, even for a franchise level product. I believe that the planned post-marketing drug utilisation study has now been approved, although I don't know whether this is national or international in scope. It's going to take a while to collect sufficient useful data, but it may eventually spur Recordati to more focused marketing efforts.

Epgonline links are simply to the local language versions of the SPC (since approval was through the centralised procedure). Some, but not all, EU member states list commercial availability on the corresponding competent authority website (look for links to the national pharmacopoeia, generally searchable).

Most, if not all of the recommendations are expected to be accepted by summer (my inbox is full of flyers for China-themed investment events and conferences). The stated ambition is to outstrip NASDAQ as a life science launchpad, and considering the recent level of ex-China biotech investment made by Chinese-managed funds, I don't think there's going to be a shortage of action. Quality of mainland Chinese companies might be a problem in the beginning (not a criticism of ability, but pre-clinical and clinical work will have been generated in a less than rigorous environment). I'm aware of several Chinese companies that can hold there in own in biologics, immuno-oncology and gene therapies. I take your point about JG's phrasing, and can only think that he had the RP situation in mind, with royalties accruing through ownership. Of course, you can (and several established companies do), purchase royalty streams prior to commercialization, but this needs deep pockets and a goodly sized herd of prospective milk cows.

All the more puzzling when you consider the proposed changes in HKSE listing rules with respect to biotech companies, which (along with the CFDA reforms) did not get a mention in JG's "outlook". Concept paper (and slide presentation here) https://www.hkex.com.hk/News/News-Release/2018/180223news?sc_lang=en For anyone with the stamina, webcast of last week's HKEX Biotech Summit here: http://www.hkexgroup.com/Media-Centre/Corporate-Events/HKEX-Biotech-Summit-2018/HKEX-Biotech-Summit-2018-Highlights?sc_lang=en

Pomander, it's down to different fields of reference. The HK and Macau approvals processes are, for historical reasons, broadly focused on quality of manufacture. That said,there's always a possibility that HK in particular may not accept clinical pharmacology or other data in the EMA dossier as being relevant to the local population. The CFDA has stated that it will consider submission data generated ex-China in in the context of its own population and with a nod to existing CFDA opinion. Japan, South Korea and some South American countries also consider the relevance of foreign drug submission data to their own populations. I referenced prilocaine metabolism on the basis that it's not something well-studied across different populations and is hence perhaps more likely to raise questions. As a safety issue, it is in the "theoretically possible " category, although there was a safeguard included in the UK online consultation form, albeit not one directly concerned with ethnicity, specifically: "Do you or your partner come into contact with aniline dyes or the pesticide naphthalene? "

Bakered, still too early to tell. The reform process has been ongoing since 2015,the primary objective to increase access to, and speed approval of foreign innovative medicines, with priority given to new cancer treatments and anitvirals. Certain clinical trial and registration changes were implemented last October, and there are a whole series of draft guidance documents under review. Broadly, the CFDA will permit trials of innovative drugs whether approved in other territories or not and will accept data generated ex-China. The CFDA administration process will be reduced to around six months (currently averages around five years before clinical study approval). Future reforms might change the picture but there's probably little of advantage with respect to Fortacin, since due to indication, generic active composition and lack of patent protection, it's unlikely to be viewed as either innovative or a priority under current CFDA criteria. If by some chance it was considered as a Class 5.1 "innovative imported drug approved outside of China", minimum submission requirements would be both a Pk and Phase III study in China. The bigger question is whether the CFDA would accept clinical pharmacology, safety and efficacy data generated in study groups not representative of the Chinese population as part of a submission or require at least some studies to be repeated in China. I can see prilocaine metabolism being an issue.