Facts of the case

5 December 2011

In 1976 I applied for the registration of Ukrain as an anti-cancer drug. Proceedings were pending at the Federal Ministry for Social Security and the Generations under GZ 921.726/01-VIII/16b/98.
Fully aware of the importance of the discovery, I named my preparation after the country in which the first steps in its development were taken – Ukraine. There are similar examples in the history of science. Lars Fredrik Nilson discovered a new element in 1879 which he named “Scandium” with reference to Scandinavia, in 1886 Clemens Winkler named the new element he had discovered “Germanium” and in 1898 Polonium was named in honour of Marie Curie’s home country Poland.
With my letter of 27 July 1981 to the Federal Minister of Health, Dr. Kurt Steyrer, (www.ukrin.com/docs/1981-07-27-brief-zulassung-1981.pdf) I sent a reminder about the status of the case and asked the minister to accelerate the registration proceedings for humanitarian reasons. I included the necessary documentation and pointed out that all conditions for registration were fulfilled as provided for by the Spezialitätenordnung (Medical Specialities Order) 1947:
a) The preparation is produced from two known substances which had already been registered in Austria and used in medical practice. Both Thiotepa as well as greater celandine alkaloids had already been in the Pharmacopeia Austriaca and the German pharmacopeia for a long time. Numerous studies have demonstrated that no free Thiotepa is present in the final product. (www.ukrin.com/docs/gutmann-1996.pdf)
b) In addition, with this letter I submitted to the minister study data from the National Cancer Institute (USA) and the Institut de Cancerologie et d`Immunogenetique (France), which clearly show that the preparation is effective against cancer cells while at the same time being less toxic than its starting substances.
c) As proof of its therapeutic efficacy in the treatment of cancer patients I submitted 60 medical histories of patients who had exhausted all other forms of treatment, 33 of them responded well to therapy.

Although the Medical Specialities Order does not demand the submission of clinical data, doctors and professors who had used Ukrain in accordance with §12 AMG (Medicines Act) were so impressed by the results of Ukrain therapy that they sent letters to the authorities urging them to pay the greatest attention to Ukrain and make it available to cancer patients as soon as possible. With registration the health insurance funds would be able to cover the costs of treatment and thus every cancer patient would be able to make a free decision about their form of therapy. Without registration the health insurance funds refuse to cover the costs of treatment with Ukrain. Therefore only those cancer patients who had the necessary financial means could benefit from Ukrain therapy.
Here are some examples.
As long ago as 1979 the Parisian doctor Dr. Musianowycz remarked about Ukrain: “The product deserves a scientific study and experimentation.” (www.ukrin.com/docs/Musianowycz_1979.pdf)
On 29 April 1980 Univ. Prof. Dr. Fritz Judmaier of Carinthia General Hospital (Allgemeine öffentliches Krankenhaus des Landes Kärnten) in Klagenfurt reported on a breast cancer patient: Findings at the beginning of treatment: 5x5 cm exulcerated supraclavicular metastasis. Subjective feeling of pressure in the area of the eyes and feeling of tension left supraclavicular… Already after 6 injections there was no longer visible exulceration although the tumour size itself was unchanged. Subjectively the feeling of tension had disappeared as well as the feeling of pressure in the area of the eyes which had existed for two years. At the last check-up on 8.4.1980 the patient was subjectively free of complaints… In summary, no serious side-effects were observed in the three patients so far treated with Ukrain…. The results so far appear to justify further attempts at therapy…“ (www.ukrin.com/docs/Manfreda_1980.pdf)
The Ludwig Boltzmann Institut für klinische Onkologie im Krankenhaus der Stadt Wien reported on 30 June 1980: „During this therapy (Ukrain) an increasing improvement in the general condition was observed, a local rise in temperature in both tumours (Os iliacum and femur) and decreasing pains so that only 3 morphium per day were needed. The patient feels better, also psychologically. Treatment is currently still continuing.“ (www.ukrin.com/docs/1980-06-30-boltzmann.pdf)

Quotation from the letter: “As the tests at the National Cancer Institute (USA) and at the Institut de Cancerologie et d’Immunogenetique (France) showed, the preparation itself is considerably less toxic that its starting substances.“

This fact could be explained with the first indications of the selective effect of Ukrain coming from tests at the Federal Institute of Experimental Pharmacology and Balneology (Bundesstaatliche Anstalt für experimentell-pharmakologische und balneologische Untersuchungen) on the different oxygen consumption of normal and cancer cells after incubation with Ukrain. This selective effect of Ukrain was later confirmed in numerous studies. So far Ukrain has been tested in comparative studies on 18 malignant and 12 normal cell lines under identical conditions (36, 38, 63, 143, 147, 149, 181, 184, 190, 245, 255). These experiments did away with all doubts with regard to the selective effect of Ukrain. The numerous studies have proved that Ukrain is the first and only anti-cancer drug that is toxic for cancer cells but not for healthy cells. This also explains why it is so well tolerated in clinical application.

With this data the material truth was clearly shown in relation to the high maligno-cytotoxic effect of Ukrain with simultaneous very low toxicity and thus its benefits in comparison to registered, highly toxic, chemotherapeutic anti-cancer preparations.

This fact was acknowledged in the letter from the Minister of Health, Dr. Kurt Steyrer, of 14 August 1981.

It was pointed out to me that only the submission of a license was necessary in order for registration to be granted (www.ukrin.com/docs/1981-07-27-brief-zulassung-1981.pdf). I immediately made the relevant application in 1981. I finally received the license in 1988 and promptly submitted it to the ministry. (www.ukrin.com/docs/Konzessionsdekret.pdf) All conditions for approval were thereby fulfilled.
There was not a single reason to delay approval of my anti-cancer drug for which thousands of cancer patients were waiting. Approval should have been granted automatically. 

L E G A L   B A S I S

According to §91 Abs 1 AMG (Austrian Medicines Act) applications for the approval of a medical speciality submitted in accordance with the provisions of the Medical Specialities Order before the AMG came into force – i.e. before 1 April 1984 – and had not been decided over this period were to be dealt with as an application in accordance with §13 AMG.
This means that applications for approval submitted before 1 April 1984 should have been further dealt with as though submitted in accordance with the AMG.

Despite this the authorities responsible at the time refused to deal with my application according to the regulations. My application of 1976 has remained undealt with until now. I was not the cause of a single reason why approval was delayed. These were all caused by the behaviour of the responsible authorities.

In the process the decision of the European Court of Human Rights in case No. 34983/02 of 24 February 2005 was also ignored.
Quote from the verdict:

“The court unanimously declares:

There are also two decisions of the European Court of Human Rights in which it was adjudged to be against European Community Law if a party makes an application submitting the required documentation but is subsequently judged in accordance with new amended legislation. The keyword “pipeline justice” was developed from these two decisions: if someone is already “in the pipeline” (such as by having made an application under the Medical Specialities Order) then he must stay in the pipeline until a decision has been made.

Pipeline Justice

In case Rs C-201/02, 7.1.2004 the European Court of Human Rights specified that the decisive point is “the time of the formal submission of application”. It is the only valid criterion because it is consistent with the basic principle of legal certainty. The European Court of Human Rights thereby decided that it is not dependent on the time at which the approval procedure is concluded but whether the approval procedure was initiated before the change of law.
(http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:62002CJ0201:DE:PDF).

The decision of the Administrative Court of 26.03.2007 on 2003/10/0080 is especially interesting. Here the Administrative Court states that only the formal criterion of the time of submission of application is consistent with the basic principle of legal certainty. (http://www.jusline.at/index.php?cpid=77cc2619465c939cd4189c33216b2d0c&feed=106794)

Since the European Court of Human Rights interpretation of European Union law is binding for all Member States, the norm of European Union law, as understood from the interpretation in the verdict, applies to all Member States – as a rule – ex tunc, i.e. retrospectively. Put another way: the European Court of Human Rights determines how a regulation in European Union Law should always have been understood by everyone. (See: Das Vorabentscheidungsverfahren vor dem EuGH. München 2005, ISBN 3-406-51574-6; Mariele Dederichs: Die Methodik des EuGH. Baden-Baden 2004, ISBN 3-8329-0694-0).

This adjudication of the European Court of Human Rights is also to be applied to my case.

According to §91 Abs 2 AMG for applications which were made under the Medical Specialities Order only “documentation in accordance with §15 Abs 1 Z 4-6“ was to be submitted. Apart from that, decisions on these applications should be based on “the documentation which was sufficient under the provisions of the Medical Specialities Order”.

The documentation under §15 Abs 1 Z 4-6 (in the AMG BGBl 1983/185 version) is:

In summary this means that the law for the basis of decisions on applications for approval made before 1 April 1984 should have been the provisions of the Medical Specialities Order (and not the AMG), as well as the fact that the documentation to be submitted as the basis for the decision was only that which was sufficient under the Medical Specialities Order.
Without delay I provided all of this additional documentation to the ministry.
The documentation “otherwise to be submitted under the provisions of the Medical Specialities Order” is laid out in § 4 of the Medical Specialities Order BGBl Nr 99/1947. (www.ukrin.com/docs/1947-spezialitaetenordnung.pdf) It can be seen from this that the requirements for documentation to be submitted with the application were very low. At the time it was not necessary to submit much documentation that is now obligatory under § 9a AMG. For instance, it was not necessary to submit non-clinical and clinical data.

It is certain that much documentation for the application for approval of Ukrain which must now be submitted under § 9a AMG was not required at that time.

This standpoint results from European Community Law, in fact from the adjudication of the European Court of Human Rights. There are also two decisions of the European Court of Human Rights in which it was adjudged to be against European Community Law if a party makes an application submitting the required documentation but is subsequently judged in accordance with new amended legislation. The keyword “pipeline justice” was developed from these two decisions: if someone is already “in the pipeline” (such as by having made an application under the Medical Specialities Order) then he must stay in the pipeline until a decision has been made.

Clinical Efficacy

Instead of granting approval, new demands were continually made.
The Pharmaceutical Advisory Board of the Ministry of Health agreed to the following studies on 23 June 1993:

“1. Open, controlled study of colonic cancer”

Every year approximately 5,200 people are diagnosed with colonic cancer in Austria and around 2,700 die of if. Since no clinic in Austria was prepared to carry out an open controlled study of Ukrain with colorectal cancer, the study was carried out in Ukraine using the protocol approved by the Pharmaceutical Advisory Board. The results of this study were submitted to the Federal Ministry of Health. 
The results of the study which were the subject of an article by Prof. Dr. Susak Y.M. “Comparison of Chemotherapy and X-Ray Therapy with Ukrain Monotherapy for Colorectal Cancer“ were also published: “The survival rate (after 21 months) of patients with non-metastising colonic cancer in the group treated with Ukrain was 78.6% and in the control group 33.3%.“ (www.ukrin.com/docs/Susak_1996.pdf)

The publication by Prof. Dr. Bondar “Comparative Evaluation of the Complex Treatment of Rectal Cancer Patients (Chemotherapy and X-Ray Therapy, Ukrain Monotherapy)”, which was also submitted to the ministry, states the following: “Prolongation morbi were found to have developed 14 months later in six patients in group 1 (25.0%), whereas in group 2 they were found in only two cases (8.3%).”(www.ukrin.com/docs/Bondar_1998.pdf)
(“14 months later progression of the disease was found in 6 patients (25%) from group 1 and only in 2 patients (8.3%) from group 2.”)
Of the 24 patients from the group treated with Ukrain, 18 patients are still alive today, more than 12 years later. (www.ukrin.com/docs/dubai2010.pdf)

“2. Clinical study of malignant melanoma (this study was only carried out as a historical comparison because all previous controlled studies of malignant melanoma had only shown a success rate of 10-20%. However, it is known that this disease can react sensitively to immunomodulating agents. Several doctors have treated malignant melanoma very successfully with Ukrain resulting in long lasting remissions. I enclose an example from Prof. Dr. P. Wodnianski)…”

No patient in the world with metastising melanoma has been cured. Nevertheless this study has still not been carried out.

Case Reports

A clinical study in accordance with §42 AMG was also approved:

“3. Clinical study outside hospitals in accordance with §42 AMG. For the clinical study of outpatients in accordance with §42 AMG various oncological diseases were to be treated with Ukrain as occur in the normal practice of town and country doctors. The analytical work in the draft of this study is brought into line with the normal possibilities of general practitioners and certain limitations such as of locations in the countryside particularly as it was to be a case of patients who had already been pretreated and were mostly in a progressive state of disease.”
(www.ukrin.com/docs/erfahrungsberichte.pdf).

Many doctors used Ukrain on the basis of §12 and §42 AMG, which was valid on 23 June 1993, and the results were submitted to the Federal Ministry of Health. (www.ukrin.com/docs/erfahrungsberichte.pdf).

Here are some extracts from their reports:

In 1996 Dr. Alois Denk wrote: “Medically it would be desirable to carry out further research on the efficacy of Ukrain and with the appropriate result allow it to benefit the public.”
In 1996 Univ. Doz. Dr. Hubert Denz reported: “In a case of pancreatic cancer we found a temporary regression of the tumour demonstrated by computer tomography... There were only very minor side-effects in the form of a slight feeling of warmth, in general the treatment was excellently tolerated... Well planned clinical studies should be called for which provide a standardised dosage, form of application, duration of therapy and documentation of the results. A Phase II study should be carried out first to evaluate the optimum form of therapy. Application with pancreatic cancer seems to make most sense because the results of chemotherapy are so far very modest and go hand in hand with considerable side-effects for patients who are mostly in any case weakened. In addition there are several positive reports about therapy with Ukrain for this tumour."

Dr. Siegfried Wagner: “As a continuation of my successful treatment with Ukrain I consider the approval of the drug Ukrain in Austria as extremely desirable.”
Prim. Dr. Hans-Jörg Klein: “For this reason I would find the approval of the drug Ukrain by the Federal Ministry extremely desirable."  
Dr. Peter Kadan: “Personally I would very much welcome approval of the drug Ukrain as well as the widespread routine application of Ukrain for tumour diseases because in my opinion – after many years of personal experience – a considerable improvement in the general prognosis … is to be expected.”
Dr. Uta Konstantopoulos confirmed: "A patient with inoperable bile duct cancer + liver metastases was discharged without further therapy after a small surgical intervention (gall bladder drainage) in Feb. 96. Since March 96 we have been injecting Ukrain. The patient is in an excellent general condition and has in the meantime been on a one-week hiking holiday and made two long-distance journeys... In summary I would like to state that Ukrain is excellently tolerated and I have seen a clear positive influence on the course of advanced disease in several patients. Therefore I very much hope that Ukrain will be approved and registered as a medicament as soon as possible.”
Dr. Omar Abu-Dayeh: "During my observations I established that the preparation Ukrain is a real help and a positive supplement to other treatments. Besides the remissions achieved it should be noted that patients feel well during and after treatment and their lives become more worth living. I thereby regard the official registration and approval of Ukrain in Austria as desirable and I endorse it most warmly."
Dr. Grazyna Nowicki (no relation): “I have been using Ukrain in my medical practice for around 7 years. Most of the approximately 15 patients who I have personally treated were cases of having exhausted all other forms of therapy and who, given up by traditional medicine, were desperately looking for a final opportunity of treatment. To begin with it should be mentioned that with all of these patients an unexpected subjective and objective improvement occurred after the first Ukrain injections, which I can in no way define as a placebo effect. The patients improved their eating and sleeping habits and reported the easing of pain so that in many cases the administration of strong pain killers became superfluous… I am including a few case reports of the most remarkable successes achieved with Ukrain…
A 67-year-old woman with metastatic breast cancer (bone and lung metastases, malignant pleural effusion and ascites) who had been discharged from hospital as an incurable case. Her general condition was pitiable. After the third therapy series with Ukrain, the doctors in the hospital established that all tumours, metastases and the pleural effusion and ascites had disappeared. The patient stopped treatment with Ukrain after the 7th series and experienced a recurrence (short-term remission) 7 months later…
It may be summarised that, also in consideration of my several years of experience at an ENT clinic abroad, I clearly observe the following: Ukrain is a therapy option for oncological diseases and should be made widely accessible if one is to maintain one's medical ethics and satisfy one's conscience. Marketing authorisation for Ukrain … should be issued …
I most urgently recommend that Ukrain be quickly approved to make this highly-effective cancer therapy widely and rapidly available to those who need it.”

Statements of assessors

The ministry demanded that reports should be drawn up on all parts of the registration dossier. The expert assessors were also suggested by the ministry.

In 1996 Dr. Walter Knapp comes to the following conclusion in his Pharmacological-Toxicological Expert Report on Ukrain: “Summarising the results of pre-clinical investigations, Ukrain can be certified as possessing an interesting spectrum of action, which could be usefully applied to the successful treatment of malignant diseases. The acute and chronic toxicity of Ukrain is low… The results of pre-clinical investigations document that the preparation is well tolerated and offers a high level of therapeutic safety. An advantageous ratio of activity to side effects can be expected. To date, clinical experience of the use of Ukrain in patients confirms the product to be safe.” (www.ukrin.com/docs/Knapp_1996.pdf)
The clinical report by Dr. Stefan Duma from 1996 states: "The results of experimental and clinical studies show the special efficacy of Ukrain therapy with adenocarcinomas. Histological and histochemical examinations of surgical specimens after therapeutic amputation of the breast with patients pre-treated with Ukrain show tumour regression caused by Ukrain through numerous focal necroses in the specimens after 20 days of Ukrain therapy... In summary it can be stated that Ukrain is effective in the treatment of malignant tumours through its selective maligno-toxic properties. Its few side-effects and immunostimulating effect could make a significant contribution to the efficacy of tumour therapy and improve patients' quality of life.”
(www.ukrin.com/docs/Duma_1997.pdf)
In his "Commentary on the Expert Report" in 1998 Harald von Eick recommended "the registration of Ukrain even if also under certain conditions": "Nevertheless I take the view that the data situation is sufficient to grant registration..." (www.ukrin.com/docs/vE_980420.pdf)
In his clinical expert's report on 16 June 1998 DDr. G. Nahler stated: “Results of those few controlled trials with Ukrain were consistently better than in control groups. Furthermore, some of the case reports describe treatment effects in patients resistant to any other therapy… Ukrain seems to be better tolerated than other tumour therapies.“ (www.ukrin.com/docs/ClinExpRep_2002.pdf)
In their chemical-pharmaceutical documentation both Mag. Kurt Vymazal as well as Dr. Gerolf Tittel found that the production of Ukrain is assured and the test method is sufficiently elaborated to confirm the quality of the preparation. (www.ukrin.com/docs/Tittel_2000.pdf).
All of these experts were recommended by the ministry. If they had been working for large companies their reports would have been accepted without a problem. It is still not clear to me why their positive reports were disregarded by the ministry in my case as a one-man business.
More than 250 scientists from 24 countries at 60 universities and research institutes have demonstrated and proved the efficacy, safety and quality of Ukrain. (www.ukrin.com/docs/Wirksamkeit2.pdf)
In view of the fact that the responsible authority has not reached a decision on my application for approval over a period of more than 35 years, I see my simple legally warranted right to a decision violated.

There has still been no decision on my application from 1976. The application has therefore remained undealt with until now. The responsible authority is therefore in default with regard to this application iSd Art. 130 Abs. 1 lit b iVm Art. 132 B-VG.

The application could have been decided at any time on the basis of the available documentation.

Breach of Article 7 of the Austrian Constitution

In 1993, i.e. 17 years after the application for the registration of Ukrain, the American company Bristol-Meyers Squibb was granted approval for the highly toxic product Taxol within the shortest period after application with the submission of only 17 case histories. Austria was the first country in the world in which Taxol was approved, even though Austria is not its country of origin. At the time of approval there were no comparative studies of Taxol with other cytostatica.

When I asked why Taxol had been approved so quickly under the same law I received the answer that it was because the application had been made for the treatment of patients who had exhausted all other forms of therapy. On 5 March 2001 I therefore made a supplementary application to the Federal Ministry of Social Security and the Generations for the registration of Ukrain as a medical speciality under the proviso “after standard therapy has failed”.

Comparison between the registration procedure for Ukrain and Taxol
(Comparisons from the Taxol information for physicians are quoted in italics.)

TAXOL: “Comparative studies with other cytostatica are not yet available.”(www.ukrin.com/docs/Taxol_de_93.pdf)
UKRAIN: Comparative studies – some of them randomised – with other cytostatica are available and in this comparison Ukrain proved itself to be an effective preparation without side effects. In a controlled randomised study of colorectal cancer with 96 patients the survival rate after 21 months in the group treated with Ukrain was 78.6%, in the group of patients treated with the standard cytostatic agent 5-Fluorouracil and radiotherapy it was only 33.3%.

In a randomised study of rectal carcinoma at the Regional Cancer Centre, Donetsk, Ukraine, 48 patients received either high-dose radiotherapy and 5-FU before the operation or therapy with Ukrain: one series before the operation and one series afterwards. During the following two years 8 patients (33.3%) who had received 5-FU and radiotherapy had regressions but only 4 patients (16.7%) who had been treated with Ukrain. Now, 12 years after publication, 18 of 24 patients (75%) from the Ukrain group are still alive.

In a controlled randomised study of inoperable pancreatic cancer carried out by Prof. Beger and colleagues at the Universitätsklinik Ulm in Germany with 90 patients, the 6 months survival rate in the Gemcitabine group was 26%, in the Ukrain group 65% and 74% in the group with combined treatment. The longest survival period in the Gemcitabine group was 19 months, in the combination group 26 months and in the Ukrain group two patients were still alive after 28 months. (www.ukrin.com/docs/beger4.pdf)

After the conclusion of the study the patients were followed up and it was found that Ukrain was very well tolerated and all patients could also be treated as out-patients. Ukrain therapy resulted in a considerable prolongation of survival time in comparison with Gemcitabine therapy alone. Combination therapy with Gemcitabine and Ukrain showed no advantage over monotherapy with Ukrain. The authors of the study conclude: “On the basis of this study we recommend that patients with advanced pancreatic cancer be treated with Ukrain.” (www.ukrin.com/docs/gansauge_2002_2de.pdf)

TAXOL: “Application is strictly intravenous because with paravenous and intra-arterial application tissue irritation and damage to the vascular wall can occur…”  (www.ukrin.com/docs/Taxol_de_93.pdf).
UKRAIN  – can be administered both intravenous and intramuscular. Necrosis does not occur with intramuscular injection due to Ukrain’s selective effect.
My supplementary application of 5 March 2001 for the registration of Ukrain as a medical speciality under the proviso “after standard therapy has failed” was rejected by the Minister of Social Security and the Generations with the decision of 25 April 2002.
There follow quotes from the notification which served as justification for the rejection of the supplementary application for the approval of Ukrain of 1986 (applicant Nowicky Pharma, a “one-man company”) and compare them with the summary of product characteristics for Taxol, a pharmaceutical concern’s preparation, which were used as the basis for its application for approval in 1993.
UKRAIN – Reason for rejection: “There is a lack of data on chronic toxicity with a sufficiently high dosage and for the question of a cancerogenic effect.”
TAXOL: “There have been no tests on the possible cancerogenic effect of Taxol. During in vitro and in vivo tests on mammal cell systems Taxol proved to be mutagenic…” In the same test Ukrain proved not to be mutagenic. (www.ukrin.com/docs/erfahrungsberichte.pdf)

UKRAIN: “In Part IV there is a lack of reliable data on the mechanism of action, pharmacokinetics and interactions with other pharmaceutical products.” This statement was contrary to the record – see above.
TAXOL: “Distribution, metabolism and secretion of Paclitaxel in humans are not fully clarified… The effect of a kidney or liver deficiency on the secretion of Paclitaxel has not been examined…”
TAXOL: “The most frequent significant side-effect of Taxol was bone marrow depression. Neutropenia … appeared in 90% of patients, severe neutropenia appeared in 52% of patients… Serious cardiovascular incidents occurred in 1% of patients, namely ventricular tachycardia, AV block, syncope and hypotonia, which in one case led to death.“
UKRAIN: “The acute tolerability of the substance appears good” (from the notification from the Minister of Social Security and the Generations of 25 April 2002). However, because the authorities did not know to what the effect of Ukrain could be attributed the application for the approval of Ukrain for patients who had exhausted all other modes of therapy was rejected on the following grounds: “In Part III it is not ascertained whether the observed effects are to be attributed to the supposed complex, to free alkaloids or to free Thiotepa.” In doing so they completely overlooked the fact that Thiotepa is a highly toxic product which is nowadays hardly used. In contrast Ukrain is an effective preparation without noteworthy side-effects. Its therapeutic index is 1250, which attests to its great safety. For this reason no cases of an overdose with Ukrain are known. The therapeutic index for conventional cytostatica is in the range of 1.4 – 1.8 (the therapeutic index is the ratio between the toxic and therapeutic dose of a medicine).
From the whole discussion with the ministry civil servants I received the strange impression that only toxic drugs which are damaging to health come into question for the treatment of cancer. A preparation which causes no serious side-effects will in no case be approved because it is not sufficiently toxic. Hofrat Univ.-Doz. Dr. Pittner wrote as follows in his report of 3 January 1989:
“The finding that Thiotepa has a genotoxic effect but Ukrain does not creates new doubt about the quality of Ukrain. Ukrain and liver homogenate of new-born rats and hamsters were applied as sterile centrifuge; the animals remained without pathological symptoms but the test set-up is extremely unusual.” (www.ukrin.com/docs/1989-pittner-gutachten.pdf)
The question arises as to whether this tendency really serves the well-being of cancer patients.
It can be seen from these quotes that two measures are used in the approval of medicines: a highly toxic medicament produced by a pharmaceutical concern is approved in the shortest time despite its doubtful effect, demonstrated on 17 patients, while at the same time the application for the approval of Ukrain of 30 August 1986, most recently modified with regard to the relevant fields of application on 7 December 2000, as well as the supplementary application of 5 March 2001 with the proviso “after standard therapy has failed” was rejected although Ukrain is an effective medicine without noteworthy side-effects which has been used with hundreds of patients and numerous randomised studies have been submitted to the ministry. Here it should be emphasised that the Federal Institute did not only did not only find fault with the lack of a placebo group but the number of 30 patients suggested by the study director was rejected as not significant. Why were only 17 patients accepted for Taxol?
In 1993 the highly toxic preparation Taxol was approved for the treatment of patients who had exhausted all other forms of therapy. My supplementary application of 2001 for the treatment of patients who had exhausted all other forms of therapy, when the efficacy, safety and quality of Ukrain had already been proved, was rejected by the same authorities. Both supplementary applications were made on the same legal basis for the treatment of patients who had exhausted all other forms of therapy. The application for the highly-toxic Taxol was approved, the application for the effective and non-toxic Ukrain was rejected.

The approval of Taxol® and the rejection of approval for Ukrain for the treatment of patients who have exhausted all other forms of therapy is a grave breach of Article 7 of the Austrian Constitution, which guarantees the same rights for all citizens in Austria.

Obstruction tactics

With the continuation of the registration procedure I gained the impression that ministry officials wanted to deny approval to Ukrain “out of spite” and even consciously wanted to prevent registration. This evidence of conscious obstruction has been documented with certain statements by high-ranking ministry civil servants. It was therefore not surprising that the submission to the ministry in 1986 of the therapy results of 450 further patients who had exhausted all other forms of treatment had no effect. In some of the patients Ukrain brought about a full regression of the tumour, as in the case of metastising melanoma described by Prof. Wodnianski. Until now no other case is known in the specialist literature of a full remission being achieved with another anti-cancer preparation in a case of a metastising melanoma. (www.ukrin.com/docs/wodniansky.pdf) Partial remissions were achieved with another group, as reported by Prof. Judmaier. (www.ukrin.com/docs/Manfreda_1980.pdf) In a third group arrest of tumour growth was achieved without noteworthy side-effects.  (www.ukrin.com/docs/1980-06-30-boltzmann.pdf) A slight improvement in the general condition was observed in other patients.
News of the successes of Ukrain spread among doctors and patients and contributed to the medicine being widely used. Mag. Kowarik heard about Ukrain in this way and declared himself willing to distribute Ukrain via his pharmacy “Zum goldenen Reichsapfel”, Singerstrasse 15, 1010 Vienna. We informed Mag. Kowarik that application had been made for the registration of Ukrain to the Ministry of Health on 28 June 1976 (www.ukrin.com/docs/1981-antrag.pdf) and that approval was expected in a short time.
Because very many patients obtained Ukrain from this pharmacy and Mag. Kowarik was informed about the astonishingly good results of Ukrain treatment with patients who had exhausted all other forms of therapy, he informed the ministry at the time and requested them to grant approval as quickly as possible. He contacted Dr. Jentzsch, the civil servant at the Ministry of Health responsible for the approval of medicines, who said however that “he will have retired before Ukrain is approved”.   (www.ukrin.com/docs/kowarik.pdf)
As can be seen from the attached timeline (www.ukrin.com/docs/chronologie.pdf), instead of granting approval in accordance with the law, endless additional illegal demands were made by the Ministry of Health. Almost as soon as they were fulfilled the ministry immediately made new demands in order to delay approval.

In the “Expert report on the application for approval of a medical speciality” of 3 January 1989 Dr. Pittner wrote:
“… pharmacology also looks sceptically at the claim that Thiotepa no longer has a cytostatic effect after conversion with greater celandine, which leads to the conclusion of inefficacy.”

This unsubstantiated accusation from Dr. Pittner of supposed inefficacy is also repeated:
“Genotoxicity was tested on bacterium mycogenes: the finding that Thiotepa has a genotoxic effect but Ukrain does not again creates doubts about the quality of Ukrain. For the in vivo genotoxicity test Ukrain and liver homogenate of new-born rats and hamsters were applied as sterile centrifuge: the animals remained without pathological findings but the experimental procedure is extremely unusual.”

The appraiser further claimed:
“Not a single controlled clinical study with Ukrain in comparison to current standard chemotherapy has been carried out.”

In the letter from the Federal Institute of Experimental Pharmacology and Balneology of 29 May 1990 it was repeated that “the lack of controlled clinical studies“ was a “serious deficiency”. Again he expressed the unsubstantiated suspicion “that efficacy is lost with the conversion of Thiotepa with greater celandine alkaloids.”

In the letter from the Federal Institute of Experimental Pharmacology and Balneology of 4 October 1991 results of the NCI screening study for Ukrain were judged as an “interesting tumour inhibiting effect”. The following was also remarked: “Similar favourable in vitro results have also been mentioned in individual reports of other authors from USA, Poland and Japan.” “The in vitro studies submitted on the anti-proliferative activity are judged so interesting that further development of the preparation is justified.”

Further: “The undersigned agrees with Mr. Nowicky that the current, conventional cytostatic therapy is very aggressive and reduces patients’ quality of life to a massive extent.”

And again: “The greatest deficiency is still the lack of controlled clinical studies to prove the efficacy, safety and fitness for purpose of Ukrain.”

In the letter from the Federal Institute of Experimental Pharmacology and Balneology of 16 November 1992 Dr. Pittner writes among other things: “In vitro there are some interesting results with Ukrain about its cytolytic activity on various cell lines…”

There are still no controlled clinical studies available. … These studies must be in accordance with the state of the art and ‘Good Clinical Practice’.”

In all his reports and letters Dr. Pittner obstinately insisted that controlled clinical studies be carried out with Ukrain although he was aware that such studies were not necessary in approval proceedings in accordance with the law at the time of application.

Dr. Pittner always made new demands for approval documentation on Ukrain. After fulfilling these demands, instead of being granted approval in accordance with the law in force at the time of application, I received only formal answers with new additional demands.
Again and again Dr. Pittner repeated his unsubstantiated accusation and vehemently opposed the approval of Ukrain:
“The institute is against the approval of Ukrain…” (3 January 1989)
“The institute is still against the approval of Ukrain…” (29 May 1990)
“… the institute must remain against the approval of Ukrain.” (4 October 1991).
“… the institute is still against the approval of Ukrain.” (16 November 1992)
“… the institute must therefore remain against the approval of Ukrain.” (8 April 1993)

Absurd Demands from the Ministry

In 1992 the results of the first clinical study with Ukrain were published in the specialist literature and submitted to the Ministry of Health. Thereupon the ministry demanded randomised clinical studies in accordance with the protocols approved by the ministry. These studies were carried out and also submitted to the ministry.
In fact the first randomised studies with Ukrain were carried out in Ukraine. (67, 112, 185) In these studies Ukrain was compared with standard therapy at the time. The first study included 96 patients with colonic cancer and was carried out in accordance with a previously drawn-up protocol approved by the Austrian authorities. In the publication about this study (67) it was directly pointed out that “the study protocol was approved by the Pharmaceutical Advisory Board of the Austrian Federal Ministry of Health, Sport and Consumer Protection.” (67 page 3). The results were submitted to the ministry.
The demand for a controlled clinical study was thereby fulfilled. Instead of accepting this study and granting approval, in his letter of 17 July 1995 the director of the above-mentioned institute Hofrat Univ.-Doz. Dr. Heribert Pittner demanded that a study be carried out with a placebo group, which is not only illegal but also unethical:
“I see the most serious deficiency in the suggested study as the lack of a placebo group.” In this letter he also confirmed that in previous studies that I had submitted to the ministry the only drawback was the lack of a placebo group: “With the current test plan you have only an open study with the same deficiencies inherent in all previous Ukrain studies.” (www.ukrin.com/docs/Placebo_1995.pdf)
In 1995 the Austrian Ministry of Science asked Univ.-Doz. Dr. Reinthaller to carry out a clinical study with Ukrain. Dr. Reinthaller drew up an appropriate study protocol. The Ethical Commission insisted on the imperative inclusion of a placebo group.
Pschyrembel Medical Dictionary (Pschyrembel Medizinisches Wörterbuch) defines placebo as follows: “Placebo, so-called dummy drug; pharmacologically ineffective, indifferent substance.”
The existence of a placebo group in the study would mean that half the patients – in this case with recurring abdominal cancer – would receive no real treatment but only water. Dr. Reinthaller regarded this demand as unethical and felt forced to withdraw from the study under these conditions.
Even a quote from the book “Guidelines for Clinical Studies” shows how ethically intolerable this demand is: “No sensible person would have the idea of comparing cytostatica with a placebo.” (www.ukrin.com/docs/placebo-buch.pdf)

Responsibility of the Ministry of Health

Among patients’ rights is included the right to be informed about their treatment, its dangers, side-effects and alternatives to this method of treatment (§ 5aKAKuG). The patient also has the right to accept or reject the treatment offered with a declaration of consent (§110 StGB).

According to Art 10 Abs 1 Z 12 of the Austrian Constitution the federal government is responsible for public health. Competence for public health is under the Federal Ministry of Health and includes the promotion of health and defence against dangers to health, health care, the drawing up of legislation for the safety of medicines and the approval of medical specialities. In the process priority is to be given to the well-being of patients, the entitlement to equal chances, meaning access to health provision for all, and also the right to prompt and effective treatment with attention paid to patients’ requirements and the preservation of human dignity.

The Ministry of Health announces on its website:
Health is among the basic rights of every person and is not only a humanistic but also a humanitarian task to keep access to the Austrian health system equal for all people living in Austria.” In contrast to this is seems like a mockery, not only of me personally but of those affected by cancer, especially patients regarded as “having exhausted all other forms of treatment” who are denied an anti-cancer preparation of which it has been known for 35 years that its efficacy, safety and quality have been proven.  Refusing treatment with Ukrain means taking away the last chance and the last hope of improvement from patients who have exhausted all other forms of therapy.

Harm to patients and Austria through the non-approval of Ukrain

Since Ukrain is approved in other countries, is the subject of 267 scientific publications and has been presented at specialist international congresses 297 times doctors licensed to practice in Austria may prescribe the preparation in accordance with §8 AMG.
Doctors who are informed about the efficacy, safety and quality of Ukrain from the specialist literature and congress reports and who are aware that Ukrain could perhaps still help their patients in a desperate situation do not dare to prescribe this preparation because patients would have to pay for treatment from their own pockets.

Because Ukrain is not yet approved the health insurance funds refuse to bear the costs of treatment which means that only more affluent patients can afford therapy with Ukrain. Free choice of therapy for cancer patients is thereby not put into practice.

A study of the economic effects of the approval of Ukrain in Austria showed that annual revenues of EUR 770,500,000 could be achieved with the treatment of only 10% of cancer patients in the European Union who had exhausted all other forms of therapy. An overall turnover in the years 2000-2010 could amount to EUR 7,705,000,000. The state of Austria could thereby have an annual income of EUR 770,500,000 only from the value added tax from the sale of Ukrain.

The existence of Ukrain’s unique properties is denied

In Austria considerable sums are spent on cancer research each year. The two important properties of Ukrain were discovered in this country: the studies of oxygen consumption with normal cells and cancer cells at the Federal Institute of Experimental Pharmacology and Balneology provided the first indication of its selective effect in 1976 (www.ukrin.com/docs/Hohenwarter_1992.pdf); and in 1998 its antiangiogenic effect was observed at the Department of Vascular Biology and Thrombosis Research (Institut für Gefäßbiologie und Thromboseforschung) at the University of Vienna. (www.ukrin.com/docs/Koschelnick_1998.pdf)
We now know a lot about Ukrain’s mechanism of action but almost all of this is thanks to studies carried out abroad. It is incomprehensible why these research findings have not attracted more attention in Austria, Ukrain’s country of origin. Clinical studies have also not been carried out in Austria. It is also remarkable that even with colonic cancer, with around 2,700 annual deaths in Austria and with the study protocol for this indication approved by the Pharmaceutical Advisory Board no clinical study has been carried out.

In 1984 the renowned Viennese dermatologist and melanoma specialist Prof. Peter Wodnianski documented the first case of a complete regression of a metastasing melanoma after treatment with Ukrain as monotherapy. No similar case of such a long-term remission is known in the specialist literature. Prof. Wodnianski asked the ministry to check possibilities for therapy with Ukrain with a clinical study in order to be able to make the medicament accessible to other patients if applicable. Around 300 melanoma patients die annually in Austria. The protocol for a clinical study with Ukrain was approved by the Ministry of Health but such a study has not been carried out until now.

The protocol for a clinical study of colorectal carcinoma was also approved by the Pharmaceutical Advisory Board of the Ministry of Health. (www.ukrin.com/docs/Arrouas_1993.pdf) Although approx. 5,200 people per year are diagnosed with colorectal cancer in Austria and around 2,700 die of it and the efficacy of Ukrain has been proven in preclinical (www.ukrin.com/docs/nci-3.pdf) and clinical studies (www.ukrin.com/docs/Bondar_1998.pdf, www.ukrin.com/docs/Susak_1996.pdf) such a study has not so far been carried out in Austria.
If anyone had doubts about the effect of Ukrain they should have initiated an appropriate study. And the safety of the preparation has been adequately proven in studies by the renowned Austrian Seibersdorf Research Centre in accordance with GLP guidelines (Good Laboratory Praxis).

Summary

Over time the approval procedure has developed into a real “tale of woe” since the ministry did not only declare itself ready to grant approval to Ukrain but on the contrary attempted to prevent the permitted dispensing of Ukrain under the exemption clause of §12 Abs 1 Z 2 AMG (now §8 Abs 2 AMG). (www.ukrin.com/docs/amg-1994-12.pdf, www.ukrin.com/docs/amg-8.pdf). Under the above-mentioned legal provisions a medical speciality that is not approved may be dispensed with the written confirmation of a doctor licensed to practice in Austria that the medicament is urgently needed as defence against a threat to life or serious damage to health. In the following years, due to orders from the ministry, numerous administrative proceedings were initiated against me, which however did not lead to a valid judgement.

The administrative decision GZ, with which my application for approval was rejected for the first time by the federal ministry in June 1995, was annulled by the Administrative Court with the finding of illegality as a result of a breach of administrative regulations. (www.ukrin.com/docs/im_namen_der_republik-1996.pdf). The decision of the European Court of Human Rights, which found a breach of Art 6 EMRK (www.ukrin.com/docs/case_nowicky_austria.pdf), also did not impress the Austrian federal ministry.

I am enclosing the documentation "NSC 631570 (UKRAIN) Efficacy, Safety and Quality”. (www.ukrin.com/docs/Wirksamkeit2.pdf) This documentation furnishes evidence of the efficacy of Ukrain and summarises the bibliography from 267 sources. The efficacy, safety and quality of Ukrain have been confirmed in a multiplicity of studies and scientific essays in numerous countries in the world, as well as by the leading Austrian research facility in the filed of the life sciences, the Austrian Research Centre Seibersdorf. The toxological tests were carried out in accordance with the current state-of-the-art and GLP (good laboratory practice) guidelines in the largest non-university research institute in Austria. 

My supplementary application of 5 March 2001 for the approval of Ukrain as a medical speciality with the proviso “after standard therapy has failed“ was rejected by the Federal Minister of Social Security and the Generations with his official notification of 25 April 2002. For these patients it means that they are no longer treated but “sent home to die”. These patients are being refused the opportunity to bring about an improvement in their condition or at least prolong their lives without the usual, well-nigh inhumane side-effects of chemotherapy.

Civil servants at the Federal Ministry of Health have consciously prevented the approval of my highly effective medicament that has negligible side-effects. Dr. Alexander Jentzsch said that “he will have retired before Ukrain is approved”. This leads to the conclusion that whatever documentation is submitted as proof of the efficacy, safety and quality of Ukrain, approval will not be given.

And his colleague Dr. Heribert Pittner also worked to this end.

Although many reports were already available from Austrian doctors which furnished evidence of the efficacy of Ukrain, such as from Prof. Wodnianski, Prof. Judmaier, Ludwig Boltzmann Institut für klinische Onkologie im Krankenhaus der Stadt Wien - Lainz and others, Hofrat Dr. Pittner disregarded them in his report of 3 January 1989 and expressed unsubstantiated doubt about the efficacy of Ukrain. By 1989 the preparation Ukrain had already been presented 30 times at international congresses and 450 medical histories of patients treated with Ukrain had been submitted to the Federal Ministry of Health.
In his report of 3 January 1989 Hofrat Univ.-Doz. Dr. Pittner wrote:
“Besides the fluctuating alkaloid content of greater celandine the pharmacologist also encounters with scepticism the claim that Thiotepa no longer has a cytostatic effect after conversion with greater celandine, which leads to the conclusion of inefficacy.”

This unsubstantiated accusation of supposed inefficacy was also further repeated by Dr. Pittner.

In this report Dr. Pittner writes about the over 400 patients (who had exhausted all other forms of therapy) who were treated with Ukrain saying that useful results were achieved with 40-50 of them. This means that 10% of patients who had exhausted all other forms of therapy could still be helped – a fact that was totally ignored. In addition, he himself confirms the safety of Ukrain in that he designates the preparation as non-toxic.

We take the liberty of quoting one of these cases.

In 1984 after his experience with Ukrain in treating patients with metastising melanoma the renowned Austrian dermatologist and melanoma specialist Prof. Dr. Peter Wodniansky remarked that this medicament can save patients’ lives. It was therefore not surprising that he felt it his duty to inform the Ministry of Science and Research, which he did on 12 June 1984. He reported on his good results and requested that the potential of Ukrain be examined in a clinical study: “This most unusual result – with a patient who is already secreting melanine in the urine, one hardly expects a few months! – impressed me so much that I asked Prof. Dr. Klaus Wolf, the head of the I. University Dermatology Clinic to test Dipl. Ing. Nowicky’s preparation clinically. Professor Wolf agreed to this test without further ado – so that I too join in this request for further support.” (www.ukrin.com/docs/wodniansky.pdf). This shows that he was aware of the efficacy of Ukrain and had recognised its material truth.

I repeat: Dr. Pittner does not doubt that “Ukrain has an interesting tumour inhibiting effect”. (www.ukrin.com/docs/19911004-pittner.pdf). He also does not doubt that Ukrain is non-toxic: “… Thiotepa no longer has a cytostatic effect after conversion with greater celandine, which leads to the conclusion of inefficacy.” And despite this he is against the approval of Ukrain: “…the institute must therefore remain against the approval of Ukrain.” (www.ukrin.com/docs/19911004-pittner.pdf)

Firstly open studies were demanded. Then controlled studies. When the results of these studies were submitted to the ministry in 1993 Dr. Pittner demanded randomised clinical studies. When these were also submitted he demanded that the study be carried out in Austria. After Austrian researchers declared themselves willing to carry out such a study in 1995 Dr. Pittner demanded a placebo-controlled, double-blind study, which appears as ethically problematic in the field of oncology: “I see the most serious deficiency in the suggested study as the lack of a placebo group.” (www.ukrin.com/docs/Placebo_1995.pdf). He thereby set up a precondition for approval which no oncologist could fulfil.
I repeat: “Placebo, so-called dummy drug, is a pharmaceutically ineffective and indifferent substance.”

The illegal conduct of the above-mentioned civil servants has not only harmed cancer patients but also the Austrian economy as well as myself. Because Ukrain has not been approved the state of Austria is losing annual tax revenues to the amount of EUR 770.500.000.

Ukrain also has Orphan Drug Status in the USA and Australia, is approved in many countries but not in Austria, its country of origin. The health insurance funds therefore refuse to bear the costs of treatment meaning that only more affluent patients can afford treatment with Ukrain. The right to free choice of therapy for cancer patients in accordance with §5a KAKuG and §110 StGB is thus not assured.

Dipl.-Ing. Dr. Wassil Nowicky