A conversation with a Rigvir flack

Over the last two Mondays, I’ve been writing about an unproven cancer therapy that I hadn’t really heard much about before. The cancer treatment is called Rigvir; it is manufactured in Latvia and marketed primarily through a Latvian entity called the International Virotherapy Center (IVC). To recap, Rigvir is an unmodified Echovirus, specifically ECHO-7, that, according to the IVC, seeks out cancer cells, replicates in them, and thus lyses the cancer cells (causes their membranes to break, spilling out the cancer cells contents, thus killing the cell), hence the term “oncolytic virus.” Somehow, mysteriously Rigvir was approved by the Latvian equivalent of the FDA in 2004 for the treatment of malignant melanoma despite what appears to have been grossly inadequate supporting evidence and then even more mysteriously placed on the Latvian Health Ministry’s list of reimbursable medications in 2011. I suspect that the reason that I didn’t look into Rigvir earlier was probably because its use had been primarily restricted to Latvia, Georgia, and Armenia. Also, there was the language barrier. Nearly everything available on the web about Rigvir is in Latvian, a situation that has only recently begun to change.

It was Antonio Jimenez and Ty Bollinger who plucked Rigvir from obscurity. Dr. Jimenez runs the Hope4Cancer Institute clinics in Baja and Cancun, Mexico, and, for whatever reason (probably profit), these clinics started offering Rigvir relatively recently. Then, Jimenez, who’s clearly worked with Bollinger in the past, must have turned Bollinger on to Rigvir, and Bollinger included it in a long segment of Episode 3 of his The Truth About Cancer (TTAC) propaganda series of videos. It was this connection and the deceptive use of patient testimonials by both Bollinger and the International Virotherapy Center to sell Rigvir that formed the basis of my second post on Rigvir last week.

As you might imagine, apparently the management of the IVC was not happy about my posts. In fact, so unhappy was the management of the IVC that within 15 hours of my first post about Rigvir going live I got an e-mail from someone named Lelde Lapa, whose title was listed as Assistant of Business Development Department at the IVC, protesting and attempting to refute my post. As I noted before, I was amazed at how fast I received such a long e-mail after publishing my post. Clearly the IVC has many Google Alerts set for Rigvir and its name and was fast to act. What followed was an exchange that currently stands at five e-mails, three from Ms. Lapa, with two responses from me, with Ms. Lapa’s tone (if it indeed was only one person writing these) becoming more strident as the exchange went on. Because these e-mails are a great insight into the thinking (such as it is) at the IVC, I decided that a most excellent way to conclude my series on Rigvir as a trilogy would be to annotate and publish these e-mails, and then to compose a final response to Ms. Lapa’s third email, at the end of which Ms. Lapa told me that I didn’t need to respond.

Clearly she don’t know me vewy well, do she?

So let’s begin. Remember that English is not Ms. Lapa’s native language; so be kind. I wasn’t kind, but not because of any difficulties Ms. Lapa might have had with English.

Rigvir strikes back, round 1

So on the afternoon after my first post about Rigvir went live, I was greeted by this in my e-mail in box:

From: Lelde Lapa < [REDACTED]@virotherapy.eu>
To: [redacted]
Subject: Blog about RIGVIR
Date: Tue, 19 Sep 2017 00:54:53 +0300
Organization: RIGVIR Development department

Orac:

Yesterday we encountered one of your blogs (https://sciencebasedmedicine.org/rigvir-another-unproven-and-highly-dubious-cancer-therapy-to-be-avoided/?utm_source=dlvr.it&utm_medium=twitter)

Due to the fact that this blog is now widely spread by non-professionals with the title – independent conclusion from international expert, we believe we have the rights to inform you that you are used now as a tool in competition wars. Which we believe was never your intention.

The medicine RIGVIR has a clinical experience for more than 50 years and it is registered for melanoma for more than 13 years and before the era of modern trials and most of the evidences is not published. Doctors and clinics in Latvia use this medicine for majority of melanoma patients in Latvia for many years. In Latvia medicine is prescribed only in national clinics and by certified doctors and they have also other alternatives, so probably they know what they do.

2 years ago we started EMA (centralised EU) commercialisation process and even obtained EU commission support from Horizon2020 grant, we also obtained EMA regulatory advice. There is no doubts about the efficacy and safety of the medicine, however we acknowledge that we miss modern trials for centralised registration and we are working on them. This was never a secret to discover.

But year ago a group of very active, mostly anonymous people appeared that started to attack us, our cooperation partners, even EU commission, spreading bias data or even lies. They are very aggressive. Part of the sources they use does not exists, part of materials are generated by them self and republished in different sources mostly social networks, then in blogs and then cross-referenced. Part of material is made as compilation of different phrases and translated in English with certain pseudo professionals on them (By the way two such persons appears also in your blog, these persons however has no proper educations, has never been involved in medicine or science). Moreover at the spring anonymous letter (your blog also indicated it ) appeared. It was signed by few professional organisations of which only 2 are related to oncology and in fact were represented by the same people, this letter contains ~80 lies and tendentious distortion of information. Unfortunately there is no author on the horizon to be responsible for aspersion, but there have been cases when TV and portals have withdrawn similar articles and information about us already.

Mostly your blog analyses openly available data, but partially it contains false information. It contains also comments of pseudo professionals or anti-PR specialists but the producer of RIGVIR was never approached for clarification or comments. Which is sad especially, referring to the statement from the blog: “Somehow I doubt Rigvir will make it that far. At least, I sincerely hope that it doesn’t….”

We believe that also blogs should be objective and respectable professors should use only proven data and also verified sources. So please consider to here also our position and obtain more information about virotherapy with RIGVIR, like clinical trial data and post-registration experience.
We do provide special trainings for doctors and medical scientists.

I hope you are interested,

Looking forward for your replay.

Best Regards,
Lelde Lapa
Assistant of Business Development Department
www.virotherapy.eu

Of course, I had no idea who this Lelde Lapa was. I couldn’t really find anything about her. A Google search of the IVC website for her name didn’t reveal anything. For my purposes, it doesn’t really matter, but I did find it odd.

I can’t help but note here that, although I do not claim to be completely objective, my bias is rather well known: I favor science as the basis of determining which medical treatments do and do not work. I make no bones about that. Moreover, I couldn’t help but immediately note that it’s pretty hard to use “only proven data” when there is so little in the way of proven data upon which to evaluate Rigvir. That was, in fact, my key problem with the drug, that it is unproven and being marketed without sufficient scientific and clinical evidence that it does what is claimed for it.

Here was my response, sent later that evening:

Dear Ms. Lapa:

The Virotherapy Institute must be very on top of its social media to have noticed my post and composed such a lengthy e-mail to me within 15 hours or so after my post went live. If you have any specific examples of errors in my post, feel free to point them out. What I see in your letter is not that; rather, it is spin, as nothing you wrote actually casts into doubt any facts included in my post or in any of my interpretations of those facts.

Yes, I used publicly available information because that’s what many bloggers do when they compose posts. Besides, I was interested in what I view as the irresponsible marketing of Rigvir for more than just melanoma, and there is plenty of that to be found on the Internet and social media. The two videos on your website that I discussed fall into that category, without a doubt. In your e-mail, you state that there are “no doubts about the efficacy and safety of the medicine,” but there are doubts—a lot of doubts—so much so that my jaw dropped when I read that. The reason is simple. You yourself said it: “…we miss modern trials for centralised registration.” Basically, you don’t have anything resembling the level of scientific evidence required before we accept any drug as effective and safe. You have no randomized double-blind clinical trials. All you have are a handful of case reports, a couple of very poorly done retrospective studies, and ancient evidence from decades ago that cannot be inspected and assessed for scientific rigor. In my country, our Food and Drug Administration would laugh at such data.

If you’re making health claims for your product, particularly the glowing claims made about Rigvir’s anticancer activity, then all that matters to me is whether there is solid evidence to back up those claims published in the peer-reviewed medical literature as indexed on PubMed. Of course, this evidence must be in the form of papers reporting improved recurrence-free and overall survival in well-designed, randomized double blind clinical trials of your product for every cancer for which a claim of efficacy has been made. I do not care about unpublished data that I cannot examine myself. I do not care about claims. I do not care about “registration,” as clearly the registration process in Latvia at the time Rigvir was registered left a lot to be desired. I do not care about pilot grants to start to work on approval by the EU. None of that matters when evaluating a therapy if there is no good clinical trial evidence supporting its efficacy and safety. Unless you can provide me with those data, I have no choice but to find your complaints about my article to be without merit.

If Rigvir has been proven safe and effective and isn’t quackery, then why are you selling it to quack clinics in Mexico and Germany? I’m serious. Hope4Cancer, for instance, is a notorious quack cancer clinic that attracts Americans with cancer. This is not in dispute and can be verified by simply reading the Hope4Cancer website and examining the treatments it offers cancer patients. Also, if Rigvir has been proven safe and effective and isn’t quackery, then why was it featured on Ty Bollinger’s “The Truth About Cancer” video series and, more importantly, why is the administration of the International Virology Center proud of being featured in his videos? Bollinger is a notorious promoter of cancer quackery. (I can provide many examples of him promoting dubious, unproven, and quack treatments for cancer.) No reputable company selling a cancer treatment scientifically proven to be effective and safe would ever want to be associated in any way with the likes of Hope4Cancer or Ty Bollinger, because it would tarnish its brand and bring it into disrepute.

In actuality, your response makes me more confident than I was originally that I was correct in my assessment. Your paranoia, for instance, is makes me very suspicious. You rail against “anonymous people” attacking Rigvir and the Virotherapy Center, but isn’t it true that the complaints to the Latvian Health Ministry came from the two main oncology professional associations in Latvia? That’s hardly “anonymous.” They are respected professional medical societies! I also have seen quite a few criticisms of Rigvir on blogs and have been able to identify everyone making the criticisms so far. Perhaps you meant The Mad Virologist, but he isn’t really anonymous either. His name is in his Facebook profile, which I found in two minutes. Complaints about “anonymous” people out to disparage a product always make me think a company has something to hide.

Finally, I understand that you and Latvia are proud of Prof. Muceniece’s accomplishments, but ask yourself this: If she were alive today, would she want her name associated with selling her discovery before it’s actually scientifically demonstrated to prolong the lives of cancer patients or cure specific cancers?

Orac

In actuality, I had no idea whether Prof. Muceniece would care what the IVC is doing. I just wanted to see if there was any sense of shame over what the IVC was doing with her invention.

Rigvir strikes back, round 2

A couple of days later, I received this. For reference, the blog by Eduards Ritums was discussed in my first post and used in part as a basis for some of my criticisms. In any case, note the somewhat paranoid tone. I also showed my e-mails to a skeptic from Latvia who has been active investigating Rigvir, who thought that the style changed enough that it might have been written by someone else. I don’t know for sure if that is the case (you can judge for yourself), but I do know that the fallacies and dubious arguments flow freely and with paranoia:

From: Lelde Lapa < [REDACTED]@virotherapy.eu>
To: ‘[REDACTED]
Subject: RE: Blog about RIGVIR
Date: Thu, 21 Sep 2017 10:03:42 +0300
Organization: RIGVIR Development department

Dear Orac

As we indicated in our last email your blog now is spread widely in Latvia as a proof that our medicine is not effective. Was it a goal of your blog?

We got impression that the blog is a part of wider campaign that is currently in place in Latvia and therefore we just wanted to warn you ASAP and protect your reputation by providing more information if you are ready to hear it.

Part of your blog is based on the article that is published by author E.Ritums initially in very specific marketing magazine for Pharmacies. This magazine is published by Medicine Information Centre (http://mic.lv/materia-medica/ ) that is not registered in the register of mass media and even provide marketing services (http://mic.lv/materia-medica/). In addition the content of this magazine (according to law in Latvia) is considered to be specialised publication and may not have public access. The author however (based on google search) is young graduate from faculty of Chemistry that in addition to this particular article has published few (~3) more small articles and hardly is respectable journalist. Particular publication consists of number of fact errors and doubtful allegations and there is no respectable or proven sources, books or reviewed publications indicated as reference. Moreover former manager (for 12 years) of the same publisher and magazine Inara Rubene ( https://www.linkedin.com/in/inara-rubene/) is presented as independent expert here. The biggest issue is, however, the fact that this article later, bypassing limited access info (according to law) to specialists, was translated (with inconsistencies) and spread widely with help of very small, non registered NGO – Skeptiskā Biedrība (https://www.lursoft.lv/lapsaext?act=URCP&ref=LurTop&regcode=&task=search&company_name=&tipas=&CompanySearchForm%5BcompanyName%5D=Skeptisk%C4%81+Biedr%C4%ABba&CompanySearchForm%5Bcountry%5D=&utf=0&general=Skeptisk%C4%81+Biedr%C4%ABba&cid=LVA_NG_PROD), that operates web site – www.skepticisms.lv. Do you consider this as trustworthy source to build part of your story on?

Please note that official page of the product RIGVIR is rigvir.com and there is no marketing at all. Page virotherapy.eu is mostly dedicated to therapy not medicine – there are news, testimonials and trainings. It is not a clinic or pharmacy to speak about marketing. Should we hide testimonials, if there are such?
In Latvia there are very strict regulations for marketing of pharmaceuticals and there is no official judgment from Latvian Health Inspection about as you say “irresponsible marketing”. Moreover the only one claim from Latvian Health Inspection, that initially was stated so, is already changed clearly stating that we cannot be responsible for third party activities.

As you know the clinical studies are done mostly for official approval of medicine and according to Bloomberg at least one third of studies are never published. So if you are clearly stating that you don’t care about unpublished data, then please adjust title of your blog to something like “Analysis of published data of RIGVIR”. Because ignoring unpublished clinical trials for more than 30 years, you simply don’t have all the facts to loudly state that our medicine is not effective or it should be avoided.

Let us clarify that medicine RIGVIR is registered in Latvia in 2004 for Melanoma, before the era of modern requirements for trials, but based on clinical trials during 30 years period in which ~700 patients was treated with the medicine RIGVIR (there is also registration in Georgia and Armenia). The medicine is used as conventional therapy in Latvian, Georgian and Armenian clinics. In addition to that, patients from all over the world are coming to Latvia or sometimes are sending relatives or trust-persons to Latvia to buy this medicine in case traditional therapies have not succeeded or are not well tolerated. Yes we do train medical doctors from all over the world and probably their patients also have acquired medicine from Latvia. We know that the medicine is effective, we have seen it working on many thousand cases and we clearly know that it has no side effects. So knowing that, should we refuse to help patients of any Doctor?

We are not company that is developing innovative solution and according to the heritage of the founder prof. A.Muceniece the medicine should be available to as many patients as possible. We are not refusing the knowledge and information to any official doctor, official clinic or patient groups. So we don’t see any problem also from appearing in The Truth About Cancer series.

Most of our critics and also yours complains are catch-22 logic – “give us evidences before you use it -> new evidences requires investments -> to provide investments we need to use medicine –> to use medicine we need to be commercialised -> but with the existing evidences you doubt us to be commercialised …” As if only rich pharmaceutical or biotechnological companies may work in the field…

You are stating that you don’t care about existing registration, but unfortunately your analysis is used to doubt the registration. Which is off course strange, because nowhere in the world rules and regulations (in our case standards for clinical trials) are used with backward date.
Yes for new registrations – we know the rules – we will provide proper RCT data, but as for now, please respect that the medicine is prescription medicine that is prescribed only in national clinics and by certified doctors for last 13 years. They have alternatives and even reimbursed ones. So obviously these doctors have deeper knowledge about the therapy with RIGVIR, than just analysis of published data, since it is used for more than 70% of Melanoma patients in Latvia.

We suggest you to learn about this therapy and try it yourself for your patients (that follows entrance criteria) as well. In such case and with your commitment to make case report and publish it, we would provide all the necessary assistance and medicine free of charge.

Best Regards,
Lelde

Gee, Ms. Lapa makes the observation that my blog post has been circulated far and wide in Latvia as evidence that Rigvir doesn’t work as though that were a bad thing! In actuality I can’t help but feel a bit of a warm and fuzzy feeling in the pit of my cold, black heart that my post has actually been circulated far and wide in Latvia. Those behind IVC will probably take this as evidence that I’m out to get them, but I’m not. I’m out to protect cancer patients. If the IVC had the goods, as far as evidence, the easiest thing for its management to do would have been to publish it or somehow show it to me and other skeptics who are concerned that Rigvir is cancer quackery. We can be persuaded, but it takes evidence.

Finally, notice that last part, in which “Ms. Lapa” tries to co-opt me, thinking that if I were to try Rigvir I would conclude that it works. I’ve noticed this pattern before, and where I’ve noticed before it isn’t flattering to Rigvir or the IVC. You see, I’ve discovered that when it comes to cancer quackery or unproven cancer treatments I seem to have special cachet because I am a cancer surgeon and researcher. Thus, from time to time, cancer quacks try to convince me to try the treatment they are selling on my own patients. In my response, I decided to stomp down hard on this offer after giving a bit of a lecture. See what you think:

Ms, Lapa,

Although I appreciate your concern about my reputation, I think I’m probably the best judge of what will or will not damage it. In other words, I’ll take my chances.

Regarding Eduards Ritums’ article, which I did cite extensively, I tend to judge an article and its main arguments far more by quality in terms of evidence, science, and reason than by who wrote it. Even though the article I read was an English language translation, Mr. Ritums’ central thesis and arguments nonetheless came across as very sound. It doesn’t matter if he’s young and early in his career and thus hasn’t published very many articles yet. In other words, who cares if Mr. Ritums published his article in a pharmacy magazine and is a new journalist? I certainly don’t. As for whether the magazine is “registered” or not, as far as I’m concerned that is a matter of your country’s specific laws and ways of doing things. It means very little to me as an American reading a translation of the article. In fact, it wouldn’t matter to me if Mr. Ritums wrote for an unregistered blog under a pseudonym if his arguments, science, and evidence were sound. Certainly, you have not demonstrated that they are not sound; you state that there are a “number of fact errors and doubtful allegations,” but, oddly enough, you have not actually specified the errors of fact or “doubtful allegations,” much less used evidence and science to show that they are factual errors or doubtful allegations. You have instead engaged in nothing but ad hominem, which is a logical fallacy. To convince me, you’re going to have to get a lot more specific and provide the evidence to back up your criticisms, something you have not yet done after two long e-mails. I find this very telling.

As for your claim that official Rigvir website is not about marketing, I beg to differ. The whole website is clearly all about marketing, as all pharmaceutical company websites are. Indeed, it looks just like any other pharmaceutical company webpage promoting its products, complete with slick videos, like the one on this page. Basically, your website looks like any of a number of websites pharmaceutical companies maintain for individual products, like Herceptin, OncoTypeDX, or various new drugs. It’s not quite as slick, but it is very similar in appearance and content. True, it doesn’t contain patient testimonials, but that doesn’t make it any less a marketing website. Regarding the testimonials on the Virotherapy Center website, as a surgical oncologist, I find them quite misleading. Insufficient information is provided to allow me to judge whether Rigvir might have had an effect, and one in particular is definitely not evidence that Rigvir had a positive effect. Again, when I accused you of irresponsible marketing, I did it from my perspective as a cancer surgeon and researcher. Again, I really don’t care what Latvian law says with respect to marketing pharmaceuticals. Clearly, from my perspective, Latvian law is far too lax if it allows you to market Rigvir.

You say that Rigvir was registered in 2004, “before the era of modern requirements for trials.” I hate to tell you this, but the basic standards for modern clinical trials were codified decades before that. In the US, it was 55 years ago in 1962 when the Kefauver-Harris Amendment to the law creating the FDA mandated that the FDA to require rigorous clinical trial evidence of efficacy and safety before it approves a drug for marketing. Are you honestly telling me that 42 years after that Latvia still didn’t require such evidence before approving a drug? If true, I find that shocking. Be that as it may, Latvia’s lax drug regulation 13 years ago is not an argument in support of the efficacy and safety of Rigvir even for melanoma, much less other cancers. Certainly, it doesn’t excuse you from selling the drug to a quack clinic in Mexico. And, make no mistake, Hope4Cancer is a quack cancer clinic, as I have documented elsewhere. (It even offers coffee enemas.) I’d suggest that, if you really want Rigvir to be accepted outside of Latvia, Georgia, and Armenia, selling it to a quack clinic to market to patients it is not a winning strategy. It will taint Rigvir with the stench of quackery. I’d highly suggest that you sever all ties with these clinics immediately, but I suspect that suggestion will fall on deaf ears.

You say over and over that you “know” that Rigvir is effective. The fact is that you do not, at least not based on science and clinical trials, which is how doctors are supposed to know which drugs work and which do not. You claim that I ignored 30 years worth of clinical trials. Whose fault is that? You haven’t published them in a form that can be critically examined. If you had, I would have critically examined them. You wouldn’t even have to translate them into English. I’m sure I could find someone to translate the data for me if you were to publish all this data. Why don’t you?

No, I will not change the title of my post. It is accurate, as far as I am concerned. I stand by my opinions and conclusions, and, yes, I still strongly believe that you should stop marketing Rigvir until such a time as clinical trials show it to be safe and effective. Certainly it should not be used for any cancer other than melanoma, and even for melanoma I don’t think you’ve shown sufficient evidence that it works to justify marketing it. Again, I say this because you can’t show me any decent scientific or clinical trial evidence to change my mind. Again, why is that? Does this evidence actually exist, or does it actually show Rigvir has such miraculous effects against melanoma? I suspect that it either does not exist or is not nearly as impressive as you claim. Indeed, there is a contradiction here. You say that 70% of melanoma patients in Latvia since 2004 have been treated with Rigvir. Why is it, then, that you could only find 52 melanoma patients treated with Rigvir for your 2015 Melanoma Research paper?

Finally, although I am intrigued by your offer to provide Rigvir for free for me to try on my patients, unfortunately I don’t see how I can do it. Let me explain to you how we do things in the US. Doctors here can’t just go around administering unapproved drugs willy-nilly to patients if we feel like it. Were I to administer Rigvir to patients without proper approvals, I would quickly find myself in deep legal trouble—and rightly so! Were I to want to administer Rigvir to patients, it would have to be in the form of a clinical trial. I would first have to submit an Investigational New Drug (IND) application to the FDA, because Rigvir is not approved in the US. The FDA would then have to approve it. Next, I would have to write a protocol for a clinical trial. Let’s say I chose to do a phase I clinical trial, which would not require randomization. That application would have to be approved by the FDA and approved by my institution, specifically my cancer center’s Protocol Review and Monitoring Committee and my university’s Institutional Review Board (IRB). Both would almost certainly say no, based on lack of evidence to justify the trial. They would want preclinical evidence in cell culture and animal models, at the very least, or more compelling human evidence. You can provide me with neither.

Of course, certainly I would be happy to review the educational materials you provide doctors who wish to administer Rigvir to patients. Maybe they would start to change my mind, although I’ll be honest with you and inform you that I doubt it. However, contrary to what you think, my mind is not closed. What it takes to open it more is high quality scientific and clinical evidence. Provide it, and perhaps it will convince me. If you continue to fail to provide it, and you’ll never change my mind. The ball is in your court.

Sincerely

Orac

Rigvir strikes back, round 3

The IVC didn’t respond right away. It took a few days. Indeed, I was beginning to wonder if Ms. Lapa was going to respond again at all, particularly after nothing arrived immediately after my second post about Rigvir. Then, just as I was about to send a quick e-mail to tweak Ms. Lapa and see if I could get a response, this hit my e-mail in box:

From: Lelde Lapa < [REDACTED]@virotherapy.eu>
To: [REDACTED]
Subject: RE: Blog about RIGVIR
Date: Tue, 26 Sep 2017 18:55:40 +0300
Organization: RIGVIR Development department

Dear, Dr. Orac

…We are very grateful for every objectively critical remark that is addressed to RIGVIR and we always are trying to provide additional information to the source in order to improve objectivity. This time we however are relay surprised that someone who calls for scepticism and ask for proves, can easily believe to articles without any proven references or sources, that contains statement from people openly in conflict of interest and that is published in non-official portals in order to avoid responsibility for aspersion. And particularly we are sad that you was never interested in our position or in our facts that we openly offered and that are not published.

During last month we have seen lots of false news and lies that was spread in Latvia in order to neglect RIGVIR, part of these news is spread under the name of respectable organisations. But unfortunately most of the stories does not have real authors. Most of this campaign is done via social networks so we need time to respond to attacks and we will inform you about the results. In the meantime we are open to organise professional seminars and conventions to share our information. For example, last Friday during the 8th Latvian Doctors Congress, satellite symposium about virotherapy and RIGVIR took place. Reports on clinical trials and post-marketing experience in clinical practice were presented to doctors. Around 5000 doctors were invited and everybody had chance to ask any question to our leading managers. We however received no question from the audience.

Regarding rigorous clinical trials, most probably the definition has changed over time. For example the 1.st RCT ever was run just after the WWII. What we today call rigorous was defined only in the late 1990ies. While for example the FDA started requiring 5 year survival data for oncologic drugs, in the early 2000 those kind of data were still available only for a portion of NDAs. However A very direct outcome of WWII was that Latvia lost its independence. As a consequence, Latvia was literally thrown decades back, as well as held back, in all aspects of an advanced society. You may find that shocking to learn in 2017, but we can assure you that was a shocking “experience” already at that time on site. And it lasted for 50+ years. A slight and minor side effect, was that regulatory requirements did not adhere to the US framework. They were the so called Soviet style, which include lack of publication as well. Today, however, Latvia is part of EMA territory with the most up-to-date regulatory requirements. Therefore, the mode of showing efficacy has changed both over time and in space. Nevertheless, the requirements regarding efficacy were and are fulfilled. And this again is approved by the Ministry of Health of the Republic of Latvia that on 4th of September 2017 issued official statement supporting that RIGVIR is registered and included in the list of reimbursed medicines appropriately (see English translation enclosed) and here is in latvian source: http://www.vm.gov.lv/lv/aktualitates/preses_relizes/5507_par_zalu_registracijas_kartibu_/

Regarding the use of Rigvir in Latvia. It may also come as a surprise to you that the medical records system in Latvia has not really changed since WWII. This, of course is not the companies responsibility. It may perhaps assist you in appreciating inclusion criteria used and the effort in managing the analysis published in Melanoma Research.

When you discuss about our clinical trials or reproach us about lack of publications we are kindly ask you take into consideration also the economic differences between USA and Latvia fully into account, for example GDP per Capita in Latvia is around 15 thousand Dollars, while in USA it is 52 thousand Dollars or for example the whole budget for melanoma treatment of Latvia is around 0.7 MUSD. In other words you know how much those things costs and you should not judge from the stand point of the most advanced economy with the highest healthcare and science budgets.

We are founders (Prof. A.Muceniece) family owned company that’s heritage is to provide this innovative treatment to any patient in the world who needs it and we will not discriminate any patient regardless from which clinic the patient comes.

In your latest blog you have analysed part of testimonials about virotherapy with RIGVIR (Please note however that Ty Bolinger’s activates are not related to us). We have seen complains that stories of our patients was just coincidence or that there were other factors behind the survival. But what if we would provide you with many dozens of such testimonials and cases? Is there something at all to convince you? This brings us back to the offer to you – to try the medicine for your patient. For early stage patient they should use medical tourism to Latvia, but with late stages or in cases where there are no other treatment solutions, you might consider in application of extended use of non-registered medicine on-name basis to use the medicine in USA. Off course all the time with your supervision to monitor closely the efficacy. This means that it would be case analysis not a clinical trial. Due to work with EMA we would not initiate any activity with FDA yet, although we have preclinical and clinical evidences to start.

We find this discussion, your blog and your activity in twitter really wired. If you suggest that there are better medicine for cancer patients, please use it. We have never limited anyone doing that. RIGVIR is a prescription medicine, patients cannot get the medicine by them self without doctor involvement.

So to wrap up – if you would like to explore virotherapy and use it as a treatment, we are ready to cooperate with you and teach you about our evidences.
But further correspondence and the exchange of opinions is not necessary any more.

Sincerely,
Lelde

Ms. Lapa (or whoever I’ve been corresponding with) might not think that an exchange of opinons “is not necessary any more” and that she can flounce off, digitally speaking, but I beg to differ. So, instead of responding right away, I decided that a public response would be more appropriate, to be unveiled this morning. So here’s my response to Ms. Lapa. I’ll be sure to send her a link to this after this post goes live. After all, why bother if the person to whom I respond doesn’t see my response?

So here we go. Here’s my response written over the weekend:

Dear Ms. Lapa:

You clearly don’t know me very well if you thought I would not respond to this. Indeed, given what Rigvir Holding and the IVC are doing, I think it’s a public service to show what you have been telling me to my readers. It’s also not true that I am not interested in your position. If that were the case, I would never have bothered to engage in this lengthy e-mail exchange. That’s the point. I’ve been trying to find out what evidence you have to support all the claims being made for Rigvir’s efficacy in melanoma and other cancers. All that’s indexed in PubMed is very thin gruel indeed when it comes to clinical evidence. It’s not at all convincing. Yet you keep claiming you have this highly convincing evidence while making excuses for not publishing it and whining about people criticizing Rigvir on social media. Well, I have news for you: That’s the world. Social media matters. You keep claiming that what’s being said about Rigvir is false, but somehow you never actually bother to prove it to be false. And do you know how you could prove that it’s false? Show us the data, just like drug companies in the US and EU have to do!

So you had a satellite symposium on virotherapy at the 8th Latvian Doctors Congress. That’s great, but not enough. A Google search shows that you had this conference but nothing about its results. Most satellite conferences publish abstracts of the work presented at the meeting, at least. Such abstracts are not viewed as being as convincing as a publication in a peer-reviewed journal indexed on PubMed, but they are at least something. After your conference, I am currently still left with nothing. It wouldn’t even matter to me if the abstracts or conference proceedings were in Latvian. Show me the data! You claim to have clinical trial results and postmarketing results presented at this conference? Publish them! After my previous two posts on Rigvir, I’m sure that I can find someone to translate them if necessary. In the end, I can’t help but wonder if your symposium was more of a marketing presentation than an actual scientific conference.

Next, I do not need a discourse on the history of clinical trials and FDA requirements for approval of drugs, as I am well aware of that history and when the first randomized clinical trials (RCTs) similar to what we do now were carried out. I mentioned the 1962 Kefauver-Harris Amendment to the law creating the FDA mandated that the FDA to require rigorous clinical trial evidence of efficacy and safety simply to point out that evidence from high quality RCTs has long been a requirement for drug approval in the US and Europe. In oncology at first that meant measuring an endpoint known as overall (or objective) response rates (ORR), which measures what percentage of the patients treated demonstrate tumor shrinkage. Unfortunately, ORR is not a great surrogate for overall survival. So by the early 1980s, the FDA started to require evidence of improvement in OS. While it is true that these days, in order to speed up the process of drug approval, the FDA has been accepting surrogates for OS, such as pathologic complete response (pCR) and granting provisional approval for drugs that produce such surrogate endpoints, I note that Rigvir has no convincing published data supporting the conclusion that it can even meet those lower standards for provisional approval.

I also do not buy your excuse that Latvia’s medical record system hasn’t changed since World War II. Believe it or not, until very recently, many US hospitals still used paper charts and relatively primitive record keeping. Many private practices still do. It took laws and incentives from the US government to prod our medical system into adopting electronic health records, and, even then, I note that we will probably never have the excellent centralized medical record systems that some countries in Europe do. As for your excuse that Latvia is a poor country. I counter that the very fact that Latvia is a poor country relative to the US and much of Europe is a very good reason that its government shouldn’t be wasting money on cancer treatments whose manufacturer cannot produce strong evidence of efficacy! Yet, since I took an interest in Rigvir recently, I’ve seen claims that up to 70% of melanoma patients in Latvia are treated with Rigvir. In a country like Latvia, that is insanity if true! Think of what could be done with all that money if it were redirected to treatments that work!

I also see Rigvir being advertised as effective against a wide variety of cancers when not even you have claimed to me that it is effective against any cancer other than melanoma. You claim that Ty Bollinger’s activities are not related, but I don’t see it that way. In making the long segment on Rigvir in Episode 3 of The Truth About Cancer (TTAC), Bollinger obviously had the full cooperation of the IVC’s leadership. He brought Dr. Antonio Jimenez with him, who runs the quack cancer clinic Hope4Cancer and is now selling Rigvir in Mexico. He had access to your clinic and interviewed luminaries such as Dr. Ivars Kalvins, your medical director Dr. Kaspars Losans, and your director of research and development Dr. Peteris Alberts, as well as three of your patients. The resulting segment was highly laudatory and presented Rigvir as a miracle cure based on dubious testimonials. Like many cancer patients who found out about Rigvir from TTAC, I had heard very little about your virotherapy before TTAC was released and view the video series as the best marketing for Rigvir I’ve seen anywhere. Somehow, I doubt that you would have cooperated so much with Mr. Bollinger if you thought his segment would do anything other than praise Rigvir and the IVC the way it did.

I conclude by again addressing your offer. I will be blunt. My opinion is that it is unethical, and I will not accept it. Basically, you appear to be paying for case reports that you can publish. My impression of this is backed up by this article on your website about grants for publications, in which the IVC announces that it is offering €5,000 “grants” for “publications on clinical studies of oncolytic virotherapy, observations or clinical cases in a publication that can be quoted in PubMed” and that the study “is intended on using oncolytic virotherapy rather than using oncolytic virotherapy in combination with other cancer therapies, medication etc.” In other words, you want case reports or studies looking only at virotherapy, which, given the doubt about Rigvir’s efficacy, would be highly unethical. I note that you also request that grant applicants “inform IVC on the publication topic and present to IVC the document draft before commencing the project and submitting it to the chosen journal.” To me this sounds as though you expect the paper to be written, regardless of whether the study has already been done or not, but in fairness I will allow that the ambiguity could be due to a poor grasp of English on the part of whoever wrote this web page.

Finally, before you express such disappointment with my blog posts and my activity on Twitter, I note that the Business Development Manager of Rigvir Holding, Kārlis Urbāns, has been attacking me on Twitter using fake news sources. He’s been quite nasty. Here are examples:

I note that he cites a post made by a notorious antivaccine blog, Age of Autism. I note that the bloggers at Age of Autism don’t like me because I routinely skewer antivaccine pseudoscience.

Here’s another example:

TruthWiki is a fake wiki maintained by Mike Adams, who runs the quack and alt right (yes, both) website NaturalNews.com and got his start selling Y2K scams. The conversation after that is quite amusing, even though I can only read it through the stilted English from computer translation from Latvian on Twitter. I note that Mike Adams has been defaming me on his website for a year and a half now and is up to around 40 lie-filled posts about me. You’ll excuse me if I don’t take your lamentations about how mean and nasty I’ve been to the IVC seriously when the BDM and CFO of Rigvir Holding is quoting fake news sources that routinely lie about me and trying to portray me as a tool of big pharma out to destroy Rigvir.

So to wrap up – if you would like to provide acceptable scientific and clinical evidence for the efficacy of Rigvir against any cancer, I am ready to cooperate with you and learn about it. Otherwise, further correspondence and the exchange of opinions are not necessary any more.

Sincerely,

Orac

After that, there’s only one last thing to do:

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