In this article I report about my personal experience and share in the discovery and development of dicyclanil (initially known as CGA-181893) and CLiK in the 1990s.
In 1985, after completing my PhD thesis and a few years research work in the Swiss Federal Institute of Technology (ETH) in Zürich, I got my first industry job in the Research Center of Ciba-Geigy Animal Health at St-Aubin, Fribourg (Switzerland). You can find additional information about Ciba-Geigy Animal Health in those years in my article on the discovery and development of fluazuron and ACATAK in this site.
One of my first tasks in St-Aubin was to manage the primary screening set up for discovering new ectoparasiticidal active ingredients. This meant testing about 300 new molecules weekly through a series of strategically selected in-vitro tests to identify those compounds with promising biological efficacy.
All the compounds to test came weekly from Ciba-Geigy’s headquarters in Basel, where the Logistics Department had collected them from the dozens of chemists that were producing such new molecules. Each compound was given a code, mostly CGA (Ciba-Geigy-Agro) or CGP (Ciba-Geigy-Pharma) followed by a six-digit number. Separately we got individual cards with the chemical formula, the name of the chemist that had synthesized it and other useful information.
After the primary screening, we hold a weekly meeting, the “Streich-Konzert”, in order to decide which of the positives should be selected for further testing, usually not more than 10% of those tested. “Streich-Konzert” means in German both “deleting concert” and “concert for strings”. For most tests we had a system of notes ranging 1 to 10, 1 being the best.
Discovery of CGA-183893 in the screening
Only a few months after my start one compound caught my attention. Its code was CGA-183893. It was not effective against ticks, mites or adult insects, but it had got a score of 1 in the in-vitro test against blowfly larvae. Further in-vitro tests showed that it was up to 30 times more active in-vitro than cyromazine and diflubenzuron, our standard larvicides in the screening in those years, and about as powerful as ivermectin, the unquestioned leader among the larvicides. Cyromazine was one of the most successful compounds of Ciba-Geigy in those years.
The molecular structure of CGA-183893 looked very much like cyromazine, but with an essential difference (see red arrow in illustrations). Whereas the central ring of cyromazine is an S-triazine (with three nitrogen atoms) the central ring of CGA-183893 is a pyrimidine (with only two nitrogen atoms). This seems like a very small difference, but such small differences usually have substantial implications in biology. Not being an S-triazine was very good news, as explained later in this story.
The fact that it was more potent than cyromazine against blowfly larvae was quite surprising, because such small changes mostly mean the loss of any efficacy. We contacted H. Kristinsson, the chemist in Ciba-Geigy’s Agricultural Division that had delivered CGA-183893 to find out how he had come to such an idea. He told us that he had synthesized it after studying the molecular structure of cyromazine and calculating that CGA-183893 should match the three-dimensional structure of cyromazine. Theoretically this should make CGA-183893 as biologically effective as cyromazine. And he was right.
Further in-vitro tests showed that CGA-183893 was also highly effective against larvae of houseflies, mosquitoes and fleas. Basically its spectrum of activity was similar to that of cyromazine, but about 30 times more potent.
And CGA-183893 showed another important difference with cyromazine. Whereas cyromazine is highly soluble in water, CGA-183893 was not. This seemed to be a very promising feature of CGA-183893 as well. To understand why, we need an update on the cyromazine business of Ciba-Geigy AH in those years.
Cyromazine, predecessor of CGA-183893: a success story in Ciba-Geigy Animal Health.
Cyromazine (CGA-72662) had been a success story in Ciba-Geigy AH where it had been discovered in the early 1970’s. Cyromazine is an analogue of atrazine, another S-triazine that was discovered by Ciba-Geigy in the 1950’s and had a potent herbicidal efficacy. Atrazine was a block-buster among Ciby-Geigy’s crop protection herbicides and for decades it was one of the most vastly used herbicides worldwide.
The fact that an S-triazine showed larvicidal properties was rather unexpected in those years, because S-triazines did not belong to those chemical classes with insecticidal properties (e.g. organochlorines, organophosphates, carbamates, amidines, etc.) known in those years. Although cyromazine had a narrow spectrum of activity (mainly larvae of Dipterans and a few other insects groups), it was highly effective and had a very low mammalian toxicity, something rather infrequent for pesticides in those years.
Cyromazine belongs to the so-called Insect Growth Regulators or IGRs (also called Insect Growth Disruptors, Insect Development Inhibitors, etc.). Within the IGRs cyromazine is usually grouped together with the chitin synthesis inhibitors (CSI). In arthropods (insects, spiders, ticks, moluscs, etc.) chitin synthesis is essential for the build up of the new exoskeleton after molting. If chitin synthesis is disturbed, arthropods will die during the molting process. Other prominent CSIs are the benzoylphenyl ureas (BPU), derivatives of diflubenzuron. But whereas BPUs actually inhibit chitin synthesis, cyromazine does not. Instead it disturbs correct deposition of chitin in the insect’s cuticle. This leads to an incomplete formed exoskeleton, which is lethal.
Up to 1985 Ciba-Geigy AH had successively launched three major parasiticidal products based on cyromazine in various countries: VETRAZIN, for the prevention of blowfly strike on sheep; LARVADEX, a feed-through larvicide for the control of houseflies in poultry manure; and NEPOREX for manure and waste treatment in livestock facilities against houseflies and other nuisance flies. The Crop Protection Division of Ciba-Geigy division had also launched TRIGARD against vegetable leafminers and mushroom flies.
Success was considerable, particularly with VETRAZIN in Australia and New Zealand, and with LARVADEX in the USA. In Australia, resistance of blowflies to organophosphates was already widespread substantially shortening fly strike protection down to 2-4 weeks, whereas VETRAZIN provided up to 12 weeks protection against fly strike. In the USA resistance of houseflies to conventional insecticides (organophosphates, carbamates, synthetic pyrethroids, etc.) was an increasing problem and LARVADEX was an excellent alternative.
Cyromazine: weaknesses & threats
But cyromazine had several weaknesses. Being very soluble in water, and used as a blowfly preventative, rainfall after treatment could significantly shorten protection. This happened regularly, particularly by rainy weather, common in New Zealand and occasionally happening in Australia as well. In some cases sheep had to be retreated, which meant additional sales, but was obviously perceived as a weakness by many users.
The high water solubility of cyromazine made it unsuited for feed-through administration to mammals. Ingested cyromazine is very quickly absorbed into blood and distributed throughout the body, both in mammals and birds. And it is also quickly excreted, mostly as unchanged parent molecule. But most is excreted through urine. In poultry, urine and feces get mixed in the cloaca and consequently the excrements of poultry treated orally with cyromazine are loaded with cyromazine, which inhibits the development of fly larvae in poultry manure. But in mammals, almost all ingested cyromazine is excreted in urine and not in the feces. As a consequence, not enough cyromazine reaches the feces of mammals to prevent development of fly larvae, i.e. cyromazine was and remains unsuited for feed-through control of manure breeding flies in cattle, swine and most other mammals. Manure has to be treated directly, a usage for which NEPOREX was developed.
Besides these technical facts, several Damocles swords were hanging over cyromazine. In the 1980s, the massive use of atrazine (see image) for weed control worldwide became an issue because unwanted atrazine residues were found increasingly in groundwater in many places. An accidental release of atrazine into the Rhine in 1986 further spoiled atrazine’s image. Cyromazine was not atrazine but belongs to the same chemical family and is also very soluble in water, where it is only slowly degraded and can therefore easily get into groundwater if it is not used properly. This issue became a serious obstacle to the registration of NEPOREX in several countries, e.g. in the EU. And we expected this issue to worsen, not to recede.
Another Damocles sword hanging over cyromazine was that one of its metabolites in poultry was melamine (see image), another S-triazine derivative. Melamine was and is still used to manufacture many household and industrial materials (dinnerware, laminate flooring, insulation materials, cement admixtures, etc.). But melamine was suspected to be carcinogenic. This didn’t prevent the approval of the cyromazine feed-through formulation for poultry (LARVADEX) in the USA, but it had been an issue during registration there and elsewhere, and remained a threat.
And finally, patent protection for cyromazine was scheduled to expire in the mid to late 1990s, depending on the country. We expected generic cyromazine to challenge our business in the major markets (e.g. blowfly control in Australia, New Zealand, UK, Ireland, etc.; feed-through control of houseflies in poultry in the US and elsewhere, etc.). Therefore we needed a follow-up product to defend our share of the business.
CGA-183893: the ideal replacement for cyromazine?
Based on what we knew about two years after its discovery, CGA-183893 seemed to be an ideal candidate as a cyromazine successor or replacement:
- 30x more potent more than cyromazine against Dipteran larvae;
- almost insoluble in water, i.e. theoretically appropriate for a cattle & pig feed-through larvicide;
- not an S-triazine, i.e. no issue-potential as an environmental pollutant or as a producer of melamine residues in food commodities.
The chemistry department synthesized numerous analogues, but CGA-183893 remained the most effective one and was finally selected for further evaluation.
Excellent news came from the first in-vivo trials with CGA-183893 against blowflies run by our colleagues in our research center down under in Kemps Creek, Australia. They were simply fantastic. More than 20 weeks protection against blowfly strike had been achieved in standardized patch tests on sheep (in vivo studies after artificial infestation), almost twice as long as with cyromazine and any other compound previously tested, including ivermectin. Further trials with simulated rainfall indicated that rain would not substantially reduce the length of protection achieved with CGA-183893.
Needless to say, that our Australian colleagues were absolutely enthusiastic about CGA-183893. It was not surprising, because blowfly prevention was the largest single ectoparasiticide market in Australia in those years (> 100 million sheep!), we were market leaders (with VETRAZIN and several diazinon products), and we expected this leadership to be challenged soon by our competitors.
In-vivo trials as a feed-through larvicide in chicken gave inconclusive results. Efficacy could be achieved, but not at the level expected from in-vitro results. In those years, Walter Häusermann, my first boss, was running these pre-clinical in-vivo studies. I remember how hard he tried to get the results that we had expected. But he couldn’t. And he found out why. The reason was that, although CGA-183893 was insoluble in water, it was also absorbed into blood and distributed throughout the host’s organism. But it was much strongly metabolized than cyromazine. And the main metabolites had no larvicidal activity. As a consequence, the concentrations of the parent molecule achieved in the host’s feces were not as high as expected and fly control was not better than with cyromazine.
The bottom line was that a new feed-through larvicide for poultry based on CGA-183893 would not achieve a significantly better efficacy than the already existing LARVADEX. The only advantage would be the absence of melamine residues and the lower issue potential as an atrazine analogue. It was questionable whether this advantage alone would justify the investment required for developing a new product.
Based on what we already knew, we believed that CGA-183893 was most likely to have the same mode of action on parasites than cyromazine, and consequently cross-resistance had to be expected. In the late 1980’s there were already cases of LARVADEX failure in poultry farms due to housefly tolerance to cyromazine. Tests of CGA-183893 on such tolerant houseflies confirmed cross-resistance with cyromazine.
Consequently we had to assume that cross-resistance of CGA-183893 with cyromazine was most likely to occur in blowflies as well. In those years, field resistance of blowflies to cyromazine had not been reported yet. This was already surprising after about 10 years of intensive use in Australia and New Zealand and we were convinced that it was only a matter of time for resistance to appear, since blowflies had already developed strong resistance to several previously used chemical classes (mainly organophosphates & organochlorines) in those countries. We obviously didn’t know that cyromazine was to become an exception regarding blowfly resistance. Nowadays, several decades after its introduction, there is still no significant blowfly strike resistance to cyromazine, neither in Australia, nor in New Zealand or Europe, in spite of massive used during those years. The reasons are not yet completely elucidated.
Additional bad news came when the Crop Protection Division concluded that they had no interest in the further development of CGA-183893. This meant that Animal Health had to fully finance the costs of the toxicity and manufacturing packages, in those years at least USD 10 mio, more than 50% of the total development costs expected.
We didn’t explore the potential of CGA-183893 as a flea larvicide. The reason was that in those years CGA-184699, another IGR had already been preferred as a development candidate for flea control. It was to become lufenuron, the active ingredient in PROGRAM and SENTINEL.
1989: Into the fridge
In April 1989 I traveled to Australia. I had to discuss with our colleagues there the next steps with CGA-183893 and other research projects as well. By then and for the reasons previously mentioned we already knew that there was no interest for continuing development of CGA-183893 for housefly control in poultry (i.e. replacement of LARVADEX or NEPOREX), and that a feed-through product for cattle and pigs was not feasible. And this had severe consequences for the future of the project.
A new blowfly product would be mainly for Australia and New Zealand, but without potential in the US and Japan, two of our strategic priorities together with Europe in those years. A blowfly product had potential in the UK and Ireland too, but our blowfly business there was still rather modest in those years.
I was aware that this would not be enough for our management to promote the project to development, regardless of the strong enthusiasm in Australia. I expected the project to be discontinued. And this is what finally happened in the next New Product Portfolio Review Meeting. However, to my surprise, CGA-183893 was not “killed”, as usually happened under similar circumstances. Instead it was put into the fridge. This meant that no substantial further work was to be done but that development may be resumed in case of significant changes in the market development. Having expected the project to be killed, I was not disappointed by the freezing, but I wasn’t optimistic about when the project may be resumed, if at all.
1992: CGA-183893 defrosted
As it often happens in large multinational companies, a substantial reorganization in April 1991 brought me from the peaceful research department in idyllic St-Aubin, to the hyperactive environment of the marketing department in the Basel headquarters. You can read more about this in my memories about fluazuron in this site. In Basle I became International Product Manager for Livestock Ectoparasiticides. This meant that I took over global marketing responsibility for the existing blowfly products, including VETRAZIN, and various diazinon formulations (e.g. NEOCIDOL & TOPCLIP).
During the three years since CGA-183893 had been frozen, sales of VETRAZIN had strongly increased. Rainy weather and high wool prizes had considerably increased the demand for VETRAZIN in Australia. And in the UK, the VETRAZIN pour-on recently introduced was also performing very well, supported by a growing public criticism against organophosphate dips, the market leaders for blowfly prevention in those years. In fact VETRAZIN became Ciba-Geigy’s number one product in these countries, as well as in New Zealand and Ireland. Supported by our colleagues there, we started lobbying the management for defrosting CGA-183893.
In September 1992 I left Basle for a 3-month stay in Australia. I went there to support our Aussie mates in some local projects as part of my training as a Product Manager. There I got a phone call from my boss in Basle asking me for ammunition to take CGA-183893 out of the fridge: defrosting was to be considered in the next meeting of the Management Committee. Fortunately I had taken all my computer files from Basle to Sydney and I could prepare a presentation that my boss in Basle held to management (he was part of it). There were no new facts about CGA-183893, and I didn’t blow up the potential sales to make it more palatable for our management. But our management now perceived the blowfly market potential with better eyes than three years ago. And they actually took CGA-183893 out of the fridge. Our Aussie mates were enchanted.
From CGA-183893 to Dicyclanil
Back in Basle, CGA-183893 became one of my major projects to work on. In those years in Ciba-Geigy New Product Projects (NPPs) were managed by New Product Teams (NPTs) of two: A Development Manager to deal with all technical aspects, and a Product Manager to take care of all marketing aspects. Soon later Hariolf Schmid joined us as Development Manager in Basel and became my partner in the NPT for CGA-183893 (and other projects). We were to share some challenges in the following years. A Formulation Manager (Walter Oechslein) and a Registration Manager (Gerhard Hool) supported the NPT.
We started to work on two formulations: wettable granules to be used for a dipping, spraying and jetting product, and a pour-on. Wettable granules were already vastly used in crop protection and had numerous advantages over wettable powders or liquid concentrates. In those years, concentrates for dipping, spraying and jetting represented >90% of the blowfly preventatives but pour-on acceptance was increasing. Consequently it made sense to work in both directions. This was also reasonable because we already had two such cyromazine-based VETRAZIN formulations, a liquid concentrate (for dipping, jetting or spraying) sold mainly in Australia and New Zealand, and a ready-to-use pour-on sold mainly in the UK and Ireland and recently launched in Australia.
Walter, our formulation specialist soon realized that it wouldn’t be that easy to get a classic liquid pour-on with CGA-183893: solubility in water was too low. And he had a great idea: to try a suspo-emulsion. This consisted in suspending the hydrophobic molecule (in this case CGA-183893) in a lipophilic carrier, and to make an emulsion of the lipophilic carrier in water. Such formulations were already used in human cosmetics and there was no particular reason why they shouldn’t work on sheep. The idea was that, once applied onto sheep’s wool, the lipophilic carrier would dissolve into the natural wool lipids and release the small particles of CGA-183893. Blowfly larvae should be killed when coming in contact with the wool lipids. An additional benefit of such a formulation was that it consisted in >90% water instead of organic solvents. However, this was a theory that had to be proven practicable and effective in the field.
In the meantime CGA-183893 got a common name, dicyclanil.
A replacement or a complement to cyromazine?
As previously mentioned, dicyclanil was being developed to defend our leadership in the blowfly market, which in those years was based on rather cheap diazinon-based products (TOPCLIP, NEOCIDOL) and on expensive cyromazine-based products (VETRAZIN). But we didn’t want to cannibalize these products with dicyclanil, particularly VETRAZIN, or at least to keep cannibalism as low as possible. The key question was, how much better the new dicyclanil products had to be to justify a price premium that would create a new market segment and this way reduce the risk of VETRAZIN cannibalization.
The bar was already set quite high: VETRAZIN had a label claim of up to 12 weeks protection against blowfly strike and was already market leader. We were convinced that dicyclanil could provide up to 20 weeks, i.e. season-long protection in many blowfly regions. But the length of the season depended on weather conditions that can change from place to place and from year to year within the same place. In some extreme circumstances the blowfly season could be even longer than 20 weeks, too much for dicyclanil. And we still didn’t know how rain-fast it would be in the field. For this reason season-long protection didn’t seem to be achievable as an official label-claim for most countries. We finally agreed that dicyclanil products had to provide at least 16 weeks protection everywhere.
To achieve it, we had to play around with the formulation and with dosing. However, safety (particularly wool residues) and profitability imposed limits to dosing. We could not discretionarily increase the price with the dose to maintain the profitability. We were quite confident that both good efficacy and high profitability would be achievable after dipping or jetting, but were much less optimistic that a pour-on would make it. We knew that the length of protection after treatment with the VETRAZIN pour-on was 2 to 4 weeks shorter than after VETRAZIN dipping or jetting.
Fortunately, the trials with the pour-on formulation were very encouraging. Walter’s suspo-emulsion approach seemed to work. In the meantime we had also found out that once applied as a pour-on, dicyclanil would spread throughout the wool, but not too far away from the application site and only quite slowly. And it was really very rain-fast. For this reason we switched to a spray-on application with a power gun and an adequate nozzle ensuring that the wool surface directly covered at treatment was larger than with the pour-on.
As usual, trouble came from where we didn’t expect it. First field trials with the wettable granules were disappointing. We finally found out that whatever amount of granules we would throw into the dip or jetting wash, the concentration of dicyclanil in the wash would not go high enough to ensure the 16 weeks of protection against blowfly strike. The reason was that the dicylcanil granules did settle out from the dip wash to the ground. To overcome it regularly stirring the dip wash with appropriate equipment would have been required, a no-go for most farmers.
Unfortunately each trial took a lot of time, because it had to run for almost 6 months, which basically meant the whole blowfly season. Changing the parameters meant waiting for the next season to try again.
We finally came to the conclusion that we could not meet the 16-weeks claim with the wettable granules and proposed to give it up and to concentrate on the spray-on.
This was a hard decision to take for our colleagues in Australia & New Zealand, because dipping and jetting were still very popular and by large the most used delivery form there in those years. But the alternative was spray-on or nothing. This and the excellent results with the spray-on formulation finally convinced everybody directly involved in the project to agree on putting all the eggs in the same basket.
From dicyclanil to CLiK: around the cliffs
In the meantime we had found a trade name for dicyclanil: CLiK. It was proposed by our Australian mates and immediately accepted by everybody. This trade name had been registered by Ciba-Geigy years ago for other purposes and was available. Everybody loved it because of the famous Aussie song “Click go the shears”.
But we had to convince the management in Basle that continuing only with the spray-on formulation would not diminish the product’s market potential. Every year we had to “defend” the project in the annual New Product Portfolio Review Meeting, when all new projects were presented to the Management Committee that decided which ones to keep and which ones to drop.
To understand the challenge it is necessary to know that since the late 1980s, the management of Ciba-Geigy had put the priority in developing new products for the so-called TRIAD, i.e. USA, EU and Japan. And the highest priority was set on Companion Animals for unquestionable reasons: this market had the biggest growth potential, Ciba-Geigy was almost absent from this market, this market was more profitable than the livestock market, and product development was cheaper for dogs or cats (e.g. no food residues studies required) than for livestock.
Until then, innovation in companion animals had been vastly neglected by most AH multinationals. There were very few really good products available for dogs and cats (this was to change soon…). Finally, the livestock business is very much weather-dependent, and our management was fed up of hearing that sales were worse than expected because of the weather. They assumed that sales of companion animal products would be better predictable than livestock products because they would not be weather-dependant, or at least less dependant than livestock products.
In the meantime we were in the mid 1990s. By then Ciba-Geigy AH had just experienced its so far largest success story ever. The launch of PROGRAM (lufenuron) in the US as the first once-a-month pill for flea prevention on dogs had been a tremendous success. It was achieved under the internal corporate slogan “THINK BIG” manifested in corresponding advertising investments.
As a consequence our management was now used to hear about sales potentials in the three-digit million range, and they liked it. But we were talking about sales potentials of only a few dozen millions, which sound quite boring to them. As you have certainly noticed, we were not thinking big enough with CLiK.
One key question they had was how we would prevent CLiK from cannibalizing VETRAZIN. After the success of PROGRAM they were not interested in spending millions just to replace VETRAZIN with CLiK. I was able to sell them the “new-segment” strategy previously mentioned. Since CLiK protected sheep during almost the whole season, it was superior enough to prize it accordingly and to create a new segment.
I also speculated that CLiK could perhaps even boost VETRAZIN sales instead of cannibalizing it. This because many people buy middle-class products just because they are neither the most expensive nor the cheapest ones, other product features beeing almost irrelevant. Until now they wouldn’t buy VETRAZIN because it was the dearest of all options. Once CLiK would be launched as the most expensive blowfly strike preventative, these people would buy VETRAZIN simply because it was no more the most expensive one anymore. Surprisingly I convinced the management and CLiK survived.
A key question for future product success was pricing. From the user’s perspective, product benefits could justify a premium, but the higher the premium, the lower the initial sales would be and the longer it would take to plateau sales. As I already mentioned, CLiK’s efficacy as a fly strike preventative depends on the coverage of the body surface at treatment: the larger the surface directly treated, the better the protection. But the increase of body surface by age is not linear. In fact, body surface increases slower than weight or age. This means that if you need e.g. 100 for treating a 25 kg lamb, you don’t need 200 for a 50 kg ewe, because the body surface of a 50 kg ewe is less than twice the body surface of a 25-kg lamb. Adjusting dosage to body surface instead of body weight meant for users that the amount needed to treat a 50 kg ewe was not twice the amount required to treat a 25 kg lamb, but only about 50% higher. In other words, treating a lamb with CLiK was quite expensive, but treating an ewe was not that expensive. This allowed us to make CLiK not excessively expensive, and at the same time keeping the profitability we had to promise to our management to make the new product more palatable for them.
At that time came the Ciba-Geigy & Sandoz merger that gave birth to Novartis, but this had no signifcant impact on the development of dicyclanil or CLiK.
Preparing for the launch
The registration package was completed around 1996 and was submitted first in Australia and New Zealand. One of my contributions to the launch was to create the labels for the new product. By that time, there was also a strong pressure from the management to make all products more consumer-like, i.e. visually more attractive and less technical. It is true that until then most Animal Health parasiticides from all companies had been sold and correspondingly designed as “chemicals” or “medicines”, with rather boring and low-profile graphics and colors. With very few exceptions, pictures (of animals or landscapes) were not used, and most labels were “tri-colored”: black, white and one color.
Other colleagues had already started upgrading the labels of livestock products working with a small Swiss packaging company. The first drafts for FASINEX and ENDEX, two successful Novartis flukicides, looked wonderful. So I engaged that company for the new labels of CLiK and also for VETRAZIN, which we wanted to upgrade as well. This part of the job proofed to be a very pleasant one. It was much cheaper than most biological or chemical studies; You got the results very quickly; It was very easy to convince everybody involved that they looked great; And my partner in the packaging company was a very competent, very efficient and very well looking young lady. The labels designed in those days are still used today without significant modifications.
1998: Other challenges
In March 1998 we organized a workshop to prepare for the launch of CLiK and to work out the marketing strategy together with our colleagues from the major countries, Australia, New Zealand, UK, Ireland and South Africa. We met for five days in a small hotel in Arlesheim, a village close to Basle, where we discussed and further specified the “new segment” strategy for CLiK.
This was my last contribution for CLiK within Novartis. Soon afterwards I left the company to become an independent consultant. Thus I missed the first launch in New Zealand in fall that year.
But already out of Novartis I worked hard in the publication of a series of scientific papers on the numerous field trials that have been carried out with CLiK in several countries. In the following two years five such papers were published mostly in journals targeting veterinarians in Australia and UK. This was also quite new for a veterinary parasiticide within Novartis AH. Whereas other multinational AH companies followed the strategy of heavily supporting new launches with a broadside of concurrent scientific papers, Novartis AH and previously Ciba-Geigy AH were used to handle scientific publishing as a third or forth priority. In fact, up to that time many managers didn’t see the benefit of publishing scientific papers to support new products and perceived publishing as basically a waste of time, tolerated to keep some researchers happy but certainly did not encourage it. In fact, I never wrote a scientific paper during all my years in Novartis (1985-1991 in R&D, 1991-1998 in Marketing), I was never asked to do it and I really had no time to do it. The same happened to most if not of all my colleagues in those years.
When I finish writing these memories sixteen years later, dicyclanil has become #1 blowfly protection product worldwide according to Novartis AH. It remains the Rolls Royce of blowfly prevention down-under and in the EU. In the meantime Novartis has launched a combination product (CLICK PLUS) with diflubenzuron to add efficacy against sheep lice, and a light version of CLiK (CLiKZIN) for farmers that don’t need more than 11 weeks protection. And as we anticipated twenty years ago, competitors have introduced numerous brands with generic cyromazine.
We took it somehow for granted that our competitors would sooner or later discover active ingredients for blowfly strike prevention as good as or even better than dicyclanil. This has not happened. Instead, only a few rather old active ingredients (e.g. spinosad, ivermectin) have been introduced that are not really very innovative and certainly not superior to dicyclanil. My personal opinion is that this is due to the fact that during the last two to three decades, most multinational AH companies have focused their R&D efforts on new parasiticides for companion animals, neglecting their livestock portfolios. The result is a very strong innovation in the market for pet parasiticides that is now crowded, and almost no innovation at all in the market for livestock parasiticides that is relying more and more on a decreasing number of active ingredients.
Also in contrast with our assumptions in those years, many alternative blowfly strike preventatives have been unexpectedly discontinued in most markets, either for safety reasons (organophosphates, synthetic pyrethroids) or following resistance problems (e.g. benzoylphenyl ureas). Also against our assumptions in those years resistance to cyromazine and dicyclanil has not become an issue in spite of their massive use. The result is that cyromazine and dicyclanil now dominate this market almost unchallenged. Things could have developed differently.
After I left Novartis I remained in contact with several colleagues in Basle, but not with those abroad. I use this opportunity to express here my gratitude to those of them most involved in bringing dicyclanil to the market, among which I particularly remember:
- Frazer Bowen, Tom Friedel, David Overend, and Geoff Williams in Australia
- Eugene Smyth in Ireland
- Rob Nottingham in New Zealand
- Barry Hyman in South Africa
- Brian Lonsdale and Phil Dobson in the UK
NOTICE. I didn't take any notices nor did I keep a diary during my years in Ciba-Geigy and Novartis. The previous pages are just memories that have survived forgetfulness but may not be accurate. They are my very personal current view of those days. Other people involved may have perceived them differently. I apologize for incompleteness or inaccuracy.
If you are interested in "insider" stories like this one on dicyclanil, you may wish to visit the articles in this site on the discovery & development of fluazuron (ACATAK) and lufenuron (PROGRAM), two additional IGRs in which I was heavily involved iduring my years in Novartis AH (1985-1998).