Interview: Clinuvel, A Company That Does The Unusual
“There will be one price and no discounts, no backroom deals, no incentives off the record.” In an interview with the Pink Sheet, Clinuvel UK’s general manager Lachlan Hay talked about the company’s unusual pricing policy for its equally unusual photoprotective therapy, Scenesse (afamelanotide), its frustrations at out-of-sync regulatory and market access systems, and how its plans for a US regulatory filing are going.
Clinuvel Pharmaceuticals Ltd. is a company that does the unusual.
Its novel systemic photoprotective product, Scenesse (afamelanotide), obtained EU approval at the end of 2014 under exceptional circumstances. There are no scientific instruments to quantify and measure the impact of the disease Scenesse treats – the rare genetic skin disorder erythropoietic protoporphyria (EPP) – or indeed the impact of the therapy itself. Scenesse was the first product where patients' views and experiences were formally integrated into the European Medicines Agency's decision-making process. Also unusually, Clinuvel has adopted a uniform global pricing policy for the product.
Last but not least, Clinuvel is a company that speaks its mind, most recently in regard to an important recent development that means Scenesse should be reimbursed across Germany, the largest European market for the product.
Clinuvel Chief Executive/Managing Director Philippe Wolgen has accused the German National Association of Statutory Health Insurance Funds (GKV-SV) of leaving “no stone unturned in its attempt to end the existence of Clinuvel.” In the Australian company’s May newsletter, Wolgen says insurers are “coordinating efforts internationally to cull health care costs, and will come up with any conceivable argument to lower prices of pharmaceuticals.” The GKV-SV, he says, is “leading European insurers in curtailing the position of pharmaceutical companies.”
The Pink Sheet interviewed Lachlan Hay, Clinuvel UK’s general manager and, like his boss, a straight talker. Among the topics covered were the company’s pricing strategy, the broader importance of getting an agreement on coverage in Germany, its ongoing frustration with UK health technology assessment body NICE, the status of the product in the US, and the need for regulators, health technology assessors and payers to listen more to patients and physicians.
Shortly after our interview, at the company’s UK offices in Leatherhead, just south of London, there was another positive development for Clinuvel. To determine whether the product should be made available under the National Health Service in England, NICE will assess Scenesse as a highly specialized technology. Clinuvel had been arguing for this approach for a long time, disagreeing with the NICE view that the product was eligible for review only under the mainstream single technology appraisal pathway.
Scenesse And EPP
Patients with erythropoietic protoporphyria, a rare genetic skin disorder, risk second-degree burns, swelling and burning if they are exposed to daylight. Clinuvel’s Scenesse (afamelanotide) works by increasing the melanin content of the skin without having to expose it to the damaging effects of ultraviolet radiation. The benefits of treatment are a reduction in light sensitivity and a consequent – but limited, according to the European Medicines Agency – increase in the time patients can spend in daylight or sunlight. No other treatments are available for the condition. The product was approved in the EU under exceptional circumstances at the end of 2014.
Partly because of the difficulty of conducting clinical studies in patients who can see the results, ie pigmentation changes, and also because patients are understandably unwilling to expose themselves to sunlight-associated pain as part of a clinical trial, Scenesse required a shift in how regulators reviewed the product, including greater consideration of patient testimony during the approval process.
The company hopes to market the product in the US but has yet to file for approval there.
Scenesse is available in Germany, Austria, the Netherlands, Italy and Switzerland. It will be some time before a NICE decision is made regarding England. In the meantime, Clinuvel is in market access talks with “a small number of Scandinavian countries”, where, says Hay, “there is certainly demand for the product”.
The following Q & A is an abridged and edited version of the interview.
Clinuvel has said the annual cost of therapy with Scenesse ranges from €56,404 ($63,546) to €84,606 ($95,355) per EPP patient per annum.
It’s bizarre to them. They’ve not seen this before. I think there’s a certain element of disbelief. [They think:] “Okay, what you’re saying publicly is this but really we think you’re doing this.”
There’s an expectation that something is happening behind closed doors, confidentially between company and payer. We’ve said from the get go, there will be one price and no discounts, no backroom deals, no incentives off the record, it needs to be fair access and transparent and that’s what we’re living up to.
We didn’t take the decision lightly but I think our genuine execution and straightness reflects how we’ve done things over an extended period of time.
Clinuvel announced in April that it had reached an agreement with the GKV-SV that should result in all state insurers (Krankenkassen) covering Scenesse.
It’s a twelve-month process basically. We went through the process [required under AMNOG, the German Pharmaceuticals Market Reorganisation Act]. There was a series of discussions, then that process went to arbitration and now we have the outcome.
It was a very transparent, structured process that they’d put in place. They said to us, this process will happen and this process will happen and this process will happen. It’s very much stepped out, that doesn’t exist here [in the UK].
“It’s bizarre to them. They’ve not seen this before. I think there’s a certain element of disbelief.” – Lachlan Hay, Clinuvel UK
Calculating the numbers affected
When we started out working with orphan products, the payers weren’t really sure what to do either. I think perhaps on several occasions they’ve been burnt by an orphan drug company, where [they were given an estimated number of patients] and then what they ended up paying for was triple [that].
When you are talking about medicines that have a high cost … you try to provide them with a realistic range. How do I come to a number of between 500 and 1,900 for Germany? I try and be as precise as I can. We give very clear estimates, so here in the UK we think there are 513 EPP patients who would be eligible for treatment.
What you try and do is take your known patient numbers, you take estimates from your treatment centers, you take estimates from your patient association, you take prevalence data and throughout all of that you come to a number and it’s only fair to provide a range. Now the narrower the range, the better it is. For EPP this is an ultra-orphan disease, so we’re not even talking tens of thousands of patients in most instances, we’re only talking hundreds or thousands.
We speak to the physicians, the treating physicians and the academic physicians and say to them, what do you think of this number? What do you make of these prevalence numbers? Is the prevalence number for country x applicable to your country?
Again, that’s something that you then have to convey back to authorities and sometimes they get it right and sometimes they get it wrong. Here in the UK, for example, I would argue that they got it wrong and we’ve had a bit of a back and forth with them on that but costing us and the patients 16 months of delay.
At a national level… all of a sudden, from a pricing perspective, you go through another review, a completely new review of your dossier despite the European [Medicines] Agency saying, well we see that there are no tools available, we accept that, we’ve spoken to patients. To have to go through this again, it’s a frustration to put it mildly.
[I think the EMA is] trying to improve the tools that exist for the review of orphan products. Our case is certainly a good one from that regard … it took them long enough, but for the first time they started talking to patients directly as part of the process. We said to the EMA for nine years, you need to speak to patients. We said it back in 2005 when we were building the program. It [only happened] in 2014 but we got there. (Also see " INTERVIEW: Clinuvel's Philippe Wolgen on Scenesse and the patient factor " - Pink Sheet, 17 Feb, 2015.)
There’s an asymmetry between a company and a regulatory authority in that we’ve done this for 12 years, we know our drug, we know our disease indication, we know the experts who will handle it and by and large, our scientific folks have become experts, respected experts, in this disease over one or two decades.
Now I walk into EMA and they’re generalists. It may be that they’ve got a dermatologist or a gastroenterologist who sits on the board that’s reviewing but the reality is they’ve never seen one of these patients before. Perhaps it’s unfair to expect them to have that same level of knowledge but there needs to be an acknowledgement of that asymmetry of information. (Also see "Diligence And Janitors Needed To Keep Europe Innovating, Says Orphan Approval Pioneer" - Pink Sheet, 22 Oct, 2015.)
There is a need to get [regulators more] invested in this. We have a clear responsibility and a clear drive to make this product – or whatever product it happens to be – available to a patient. I don’t think there’s the same level of drive from a regulatory perspective.
The UK And NICE
At the moment, I don’t have a clear end date for a decision in England and that frustrates me but it frustrates patients even more.
We started speaking with NICE around the time the product was approved. We are still in that process so again, there’s this delay. You have a product which is approved in 2014, you and I are having a conversation in the middle of 2017, the timeline that we received from NICE is that the product might not be available until 2019. All of a sudden, the social mandate that I get from the EMA for a 10-year exclusivity is cut down to five years. How am I supposed to react to that?
Again, it comes back to that level of expertise. I’m not saying that a pharmaceutical company should have carte blanche to do what it pleases. There needs to be a system that exists and is responsible and is transparent but I don’t think we have that at the moment.
You can’t expect them to be perfect but … if you say something publicly, you have to do it, that’s my genuine view, and if that’s not happening within any organization then there needs to be change.
“It hasn’t been a transparent process. Mistakes have been made and apologies haven’t been given.”
I can tell you about EPP, but why not speak to a doctor who has spent twenty or thirty years trying to manage this disorder [to find out] why it is that that particular physician wants a treatment, demands a treatment?
You need to bridge that asymmetry of knowledge somehow. [That may not be possible] in the space of two or three months ... but [you have to see whether you can] at least get them to see what you’ve seen over a decade and try and integrate that into part of the discussion. I still don’t think NICE, for example, is capable of doing that.
Clinuvel monitors the ongoing use of Scenesse in EPP patients under an indefinite post-marketing authorization program. This includes post-authorization safety study (PASS) protocols and a European EPP Disease Registry.
Scenesse has orphan and fast-track status for the EPP indication in the US, where in July last year the Food and Drug Administration said it would allow Clinuvel to file a rolling New Drug Application for the product. (Also see "PIPELINE WATCH: 13 Approvals, Two Filings And Two Launches" - Pink Sheet, 10 Jul, 2016.)
Correspondence with the FDA has been frequent during preparation of the rolling NDA filing. Again, it’s a similar process. It took us 10 years to get the FDA to speak to patients. There’s a learning experience that is happening on behalf of the authorities in the US and you can argue about whether it’s happening fast enough but the same engagement by the regulator, a process that we went through in Europe, will have to happen in the States.
“Let’s be honest, the FDA wants to ensure that the FDA reviews drugs for Americans.”
I don’t, by any stretch, denigrate what’s been achieved thus far, I think it’s phenomenal, the folks who have worked to get this approved, but I’d like to think that we can treat children. I would like to think that we’ve got our first pediatric trials in two to three years.
I think once you are able to treat all of those patients that you think you can help clinically, that’s success.
From the editors of Scrip Regulatory Affairs.