Medical Resource Value Appraisal for Leucojum aestivum in Turkey

Abstract

In this study, we investigate the medical and economical value of Leucojum aestivum. Leucojum aestivum contains the alkaloid galanthamine, which is one of the main active substances in Reminyl, a commonly used drug for the treatment of Alzheimer’s disease (AD). In this analysis, we estimate that there are 13 million mild to moderate patients with Alzheimer’s who use Reminyl. Our results suggest that the market change value of L aestivum required for 1 unit of Reminyl is US$62. The value of total change of galanthamine and L aestivum is estimated to be US$18.6 billion per year. Alzheimer’s drugs that use L aestivum are relatively expensive, ranging in cost from US$183 to more than US$400 per month. The minimum annual cost of this is US$2196 per person for “patients with mild and moderate stage AD.” The using value of 6 million units of L aestivum bulbs, which is the amount exported from Turkey, is estimated to be US$27 million per year. The determined value for L aestivum is equivalent to the value of a rare flower that can be used to treat the serious illness of AD.

Introduction

Galanthamine is organically obtained from natural resources such as the Leucojum, Galanthus, and Narcissus genera, which belong to the Amaryllidaceae family plants. Leucojum aestivum, used for the production of galanthamine, is native to South Africa and Mediterranean regions as well as to areas in Eastern Europe and Western Asia. In Turkey, the natural habitats of L aestivum are in Thrace, the North Anatolian region, and around Beysehir. Leucojum aestivum plants grow in areas that are humid and semishaded, such as swamps and wetlands, and that are between sea level and 1100 m. The plant, which is a close relative of snowdrop flowers, grows with bulbs or seeds and usually blooms in March to June (Figure 1). The number of bell-shaped flowers per plant usually varies from 1 to 5. ² There are around 10 distinct types of Leucojum, but only L aestivum grows in Turkey. ^{2 –8}

Figure 1.

Pictures of Leucojum aestivum (Photo M. Koyuncu ²² ).

Galanthamine is an acetylcholinesterase (AChE) inhibitor that reduces the action of AChE and thus increases the concentration of AChE in the brain. This alkaloid is the main active component of Reminyl, which is used for treatment of Alzheimer’s disease (AD). Alzheimer’s disease is a syndrome that destroys intellectual and social capabilities in daily activities, distorting memory, perception, attention, language, and problem-solving skills. ^{9 –14} According to the Alzheimer Association, there are approximately 25 million patients with mild, moderate, and severe AD worldwide. Turkey has approximately 500 000 patients with AD, but only 100 000 of these patients with AD utilize medicinal therapies because of the lack of health insurance, low income, and high drug price, which limits access to AD treatment drugs. ¹⁵ An additional factor that limits access to AD drugs is that these drugs cannot be produced synthetically because they are plant-based drugs.

In historical studies, research has focused on the chemical features of the alkaloids contained in L aestivum. Medical resource value studies and studies on the sustainable production of medical plants have also been limited. These limitations make a correct evaluation of production processes of these plants more difficult. At the same time, the pharmaceutical industries have started to take greater interest in this area. In this sense, it is important to set guidelines dictating sustainable usage of these medical plants.

The pharmaceutical industries are particularly interested in the galanthamine and L aestivum plants because they create an economic input, and this increases the demand of the plant. In this context, the high demand for AD treatments has made Leucojum commercially valuable and has revealed the medical resource value of this plant. The medical resource value is assigned to ecosystem goods that contain either directly active substances or inactive additives that are used in medicine. ^3,5,13

Alzheimer’s disease causes cognitive and social impairment and galanthamine can help in this regard. It is important to consider the value of galanthamine’s ability to ease cognitive and social impairment, how it affects patients’ socioeconomically, and how easily the patients are able to access to the drug. In this sense, I determined that the medical resource value of L aestivum depends on the “galanthamine” alkaloid as well as the market value of the AD treatment. Additionally, I analyzed how the market value of L aestivum corresponds to the habitat pressure of this species and the importance of the medical value of galanthamine for developing countries like Turkey.

Materials and Methods

The market price method approach is utilized to determine the medical resource value of L aestivum. This approach is commonly used to determine the quantitative or qualitative exchange value of goods and services that are derived from limited resources. ⁵ This method is based on the willingness of producers and customers to pay. ^3,10,11 This model considers the market value of Reminyl, which is used to treat AD, and the number of patients who take this medicine. The first step is to determine the total market exchange value of Reminyl. This model primarily determines changes in the total market value (Equation 1). ^{5 –12}

Accordingly,

$$\mathrm{T}\mathrm{M}{\mathrm{V}}_{\mathrm{R}}\mathrm{=}\sum \mathrm{M}{\mathrm{V}}_{\mathrm{R}}\times \mathrm{T}{\mathrm{C}}_{\mathrm{T}}\mathrm{,}$$ 1

where TMVR is the total market exchange value of Reminyl; MVR is the market value of Reminyl; and TCT is the total consuming time of Reminyl.

The market value of Reminyl is determined by variables such as the cost of galanthamine and the inactive ingredients, the packaging, transport, and distribution costs, and the costs of acquiring patents (Equation 2). ^12,16

Accordingly,

$$\sum \mathrm{M}\mathrm{V}{\mathrm{E}}_{\mathrm{R}}\mathrm{=}\sum \mathrm{(}\mathrm{V}\mathrm{I}{\mathrm{A}}_{\mathrm{R}}\mathrm{+}\mathrm{V}\mathrm{R}{\mathrm{M}}_{\mathrm{R}}\mathrm{+}\mathrm{V}{\mathrm{H}}_{\mathrm{R}}\mathrm{+}\mathrm{V}\mathrm{T}{\mathrm{D}}_{\mathrm{R}}\mathrm{+}\mathrm{V}{\mathrm{P}}_{\mathrm{R}}\mathrm{)}$$

$$\mathrm{V}\mathrm{R}{\mathrm{M}}_{\mathrm{R}}\mathrm{=}\sum \mathrm{M}{\mathrm{V}}_{\mathrm{R}}\mathrm{-}\sum \mathrm{(}\mathrm{V}\mathrm{I}{\mathrm{A}}_{\mathrm{R}}\mathrm{+}\mathrm{V}{\mathrm{H}}_{\mathrm{R}}\mathrm{+}\mathrm{V}\mathrm{T}{\mathrm{D}}_{\mathrm{R}}\mathrm{+}\mathrm{V}{\mathrm{P}}_{\mathrm{R}}\mathrm{)},$$ 2

where MVR is the market value of Reminyl; VIAR is the inactive additive value; VRMR is the raw materials value; VHR is the handling value; VTDR is the cost of transportation; and VPR is the patent value.

Results and Discussion

The production of Reminyl includes research and development (R&D) steps, such as the isolation of the active substance (galanthamine) and the processing of the inactive substances. These steps require biochemistry laboratories and equipment, labor for manufacturing, and the industry for processing of the natural substances. Reminyl (galanthamine) was developed through a series of individual and social steps that required both abstract and concrete forms of labor (Table 1).

Table 1.

Historical Development of Galanthamine as a Clinically Used Medicine. ⁹

Year	Development of galanthamine
1980s	Preclinical development. Researchers searching for novel AD treatments began investigating the therapeutic potential of galanthamine
1990s	Clinical development of galanthamine into a medication for AD
1996	Sanochemia Pharmazeutika obtains the first patent for the synthetic process of producing galanthamine
1997	Sanochemia begins collaborating with a Belgium-based company (Janssen Pharmaceutica) and an emerging British Company (Shire Pharmaceuticals Group)
2000	Galanthamine is first approved in several countries (Iceland, Ireland, Sweden, United Kingdom) for the treatment of AD
2003-2004	Galanthamine (Reminyl) is produced and used to treat patients with AD
2006	Galanthamine is approved for usage in Turkey

Abbreviation: AD, Alzheimer’s disease.

Further assessments of the usage and exchange value qualification in markets require about 8 to 10 years due to the time necessary for isolation and processing of galanthamine and the delay until the medicine is widely available to patients. The cost of this R&D for a medical firm is about 1 million dollars per year. ^{1,17 –19} In addition to these costs, it is necessary to consider that only 1% of active substances are actually placed on pharmacy shelves.

Galanthamine has been an important part of the medical industry under the brand name Reminyl and has created exchange value price in markets. This is taken as US$ 92. ¹⁹ This is based on the drug’s prospectus, ²⁰ the research of Heinrich and Teoh, ⁹ and the assumption that patients with mild to moderate AD took 2 daily doses of the “Reminyl” drug, which contained 8 mg of galanthamine. Possible complications have been ignored, given that there has not been any reported risk in patients with AD who consume this drug. Patients who were not included in this model include patients with AD who are “severe (late stages)” and “patients who did not use the Reminyl for various reasons.”

According to the research model, the monthly drug cost is US$183 per person for approximately 13 million mild to moderate patients with AD worldwide. Accordingly, the total annual market exchange value is US$2196 per person, which is a total of US$28.5 billion per year for all 13 million patients with mild to moderate AD (Table 2). The total amount of medicine produced is around 300 million units/year and 6 million of these units are produced in Turkey. At least 600 000 of these units are purchased by consumers in the markets, which makes the using value US$55 million per year.

Table 2.

Exchange and Using Evaluations of Galanthamine for Patients With Mild to Moderate AD.

Generic Name and Dose	Galanthamine (Reminyl) Tablet 8 mg
Brand name	Generic
Frequency of use per day	2
Minimum average usage time	1 year
Per unit Reminyl exchange value, US$a	91.5
Mild to moderate patients with AD, million	13
Average monthly cost, US$	183
Per unit Reminyl annual market exchange value, US$ per person	2196
Total annual market exchange value, billion US$	28.5
Amount of drugs on the market, million unit	300
Annual market exchange value of galanthamine, US$	62
Total annual market exchange value of galanthamine, billion US$	18.6
Amount of L aestivum used for galanthamine extract, units	14
Annual market exchange value of 14 units of L aestivum, US$	62
Demand flexibility of galanthamine	0
Substitution value of galanthamine	0
Substitution plants for L aestivum, US$b	55 per year for Galanthus ssp and Narcissus ssp

Abbreviations: AD, Alzheimer’s disease; L aestivum, Leucojum aestivum.

^aPrices reflect the nationwide retail average for January 2012, rounded to the nearest dollar. Information was derived by Consumer Reports Best Buy Drugs from data provided by Wolters Kluwer Pharma Solutions, which was not involved in our analysis or recommendations.¹⁹

^bAccording to Demir, the using value and potential using value of Galanthus ssp, which is grown in Turkey, were US$55 per year. ⁶ Galanthus is therefore a potential substitute for Leucojum aestivum as a source of galanthamine.

For each unit of Reminyl, the inactive additives comprise 90% of the actual pills. The active compounds are combined with these chemical substances, packaged into capsules, and readied for distribution. The next steps involve providing a market for the medicine, distributing the medicine to the appropriate regions, and then transporting the medicine to pharmacists and pharmacy stores. All of these steps are essential elements that affect the exchange value of the medicine in the market. When the total of these costs is removed from the unit price of the medicine, the market exchange value of galanthamine can be calculated. This value is estimated to be US$62 per unit of medicine per year. Based on the total production amount, the total market exchange value of galanthamine is determined to be US$18.6 billion per year. As each unit of Reminyl includes 224 mg of galanthamine, the unit/g value of galanthamine is US$140. This exchange value of galanthamine reflects the medical resource value of L aestivum. A total of 60 000 bulbs of L aestivum are required to obtain 1 kg of galanthamine (dry weight).

Conclusion

The results of this study suggest that the market exchange value of the galanthamine drug is US$62 per unit of drugs/year, and the total exchange value of the galanthamine is US$18.6 billion per year. This exchange value of galanthamine also shows the medical resource value of L aestivum that is isolated from galanthamine plant. According to the obtained data, the medical resource value of L aestivum is approximately US$4.5 per unit. All these data show that the Alzheimer’s drugs that use L aestivum are relatively expensive, ranging in minimum cost from US$183 to more than US$400 per month. This drug’s minimum annual cost for patients with “mild to moderate AD” is US$2196 per person, which is quite high.

A total using value of 6 million units of L aestivum bulbs are exported from Turkey each year, which is equivalent to a value of US$27 million per year. Today, the export income of Turkey obtained from L aestivum is US$600 000 per year. ²¹ The commercial value is quite insufficient to makeup for the pressure and the destruction of the plant’s habitat. The origin countries of plants should be included in the R&D processes and the regulations of the patent and privilege rights. In this way, the supply and demand balance will lead to a decrease in production costs, affecting the drug prices positively. This situation will make it easier for patients with AD who have a low income and no health insurance to access the drug. Thus, patients will have more benefit from the treatment services. Of note, if a patient does not get this drug continuously, they may have adaptation problems for the rest of their life.

It is my hope that the current study will guide future work by contributing to the limited number of studies on medical plant valuation. Researching the economic value of medical plants will increase awareness and contribute to the implementation of sustainable policies regarding the usage of plant genetic resources. Development of such policies can curb the habitat pressure on plant species due to excessive demand. Thus, economic valuation research is essential for the prevention of habitat destruction. In doing this research, plants should be evaluated biologically and also socioeconomically. In this respect, this research provides an important contribution to the literature. This study suggests L Aestivum is a rare flower, grown in Anatolia, that challenges a very serious disease, a very important value, indeed!