The development of oncological drugs prescribed on an outpatient basis in the statutory health insurance system until 2016

The expenditure of statutory health insurance on medicines for the treatment of cancer is always the focus of discussion (Neller 2013). A report prepared on behalf of the Federal Ministry of Health on the question of ensuring efficient drug supply in oncology shows that an increase in costs for statutory health insurance is to be expected in this area (Glaeske et al. 2010). The prognosis of future medical costs in the oncological field is also important internationally. Mariotto et al. (2010) considers in particular the demographically related additional costs of cancer treatment in the USA. Yabroff et al. (2011) point to the additional consideration of indirect costs as a result of cancer therapy. These are described by Featherstone et al. (2010) for a consideration of costs in the United Kingdom (UK). The demographically-related annual cost increases between 2008/2010 and 2020 are estimated in these publications at 1.0 % to 2.5 %. Global observations with a focus on the pharmaceutical market and taking new launches into account assume higher annual increases (6.9 % between 2010 and 2016) (Business Insight (2011)), which are also expected in Germany (Höer et al. 2010). The aim of the analysis currently presented is to create a current forecast for the expected development of sales and consumption of statutory health insurance (GKV) for oncological drugs dispensed on an outpatient basis until 2016.

>> The data basis was the national regulation information (NVI) of the company INSIGHT Health, which depicts over 99 % of the statutory health insurance drug market dispensed via the commercial pharmacies and billed via pharmacy data centers.
The analysis included the aggregated data of the therapeutic segments L01 (antineoplastic agents) and L02 (endocrine therapy) according to the WHO ATC classification at the level of individual active substances or fixed combinations. The sales and consumption data related to the outpatient GKV medicines market.
At the time of the analysis (February 2013), the monthly sales (basis: pharmacy sales price (AVP)) as well as the prescriptions of finished medicinal products between January 2003 and October 2012 and of oncological preparations between April 2010 and October 2012 could be taken into account. The quantities of DDD (Defined Daily Doses) dispensed were calculated for the relevant prescriptions (Häussler et al. 2013). In order to close the data gaps for the years 2010 (preparations) and 2012 (preparations and finished medicinal products), the missing monthly values were estimated.1
Forecast of sales and consumption of
oncological drugs
Segments of the outpatient oncology drug market
For the forecast of sales and consumption development, the oncological drugs were divided into the following segments: endocrine therapy (L02), targeted therapies (L01, monoclonal antibodies (MAB), protein kinase inhibitors (PKI) and bortezomib), conventional cytostatics (other chemically defined active ingredients). L01) and mistletoe preparations (ATC code L01CP01).
A forecast was made for all active ingredients in these segments on the statutory health insurance market in 2012. For the segments of targeted and endocrine therapy, the expected consumption and sales were modeled individually for each of the 25 and 18 active ingredients. For the conventional cytostatics segment, the 20 active ingredients, which accounted for 90% of sales in 2012, were examined individually. For the remaining 46 active ingredients, the analysis was carried out at an aggregate level. In the mistletoe preparations segment, all active ingredient variants were analyzed in aggregate.
Creation of time series for consumption and prices
Time series were created from the available monthly consumption and price data for the individual active ingredients, with the values generally being aggregated at annual level. The consumption was expressed as the sum of the daily doses delivered (DDD), the price as the quotient of the aggregated sales and consumption sum.

Factors influencing price and consumption development
To improve the forecast, relevant factors were taken into account that could directly influence both price and consumption trends up to 2016.
The influencing factors included epidemiological factors such as the expected number of patients, the competitive situation on the markets and the number of patent expirations and new launches. To estimate the expected number of patients, the information on target populations mentioned in the benefit assessments according to Section 35a SGB V of the Federal Joint Committee (G-BA) was used and compared with the actual consumption. If there were significant deviations, the expected consumption was modeled based on the observed consumption. The development of other oncological active ingredients served as guidance.
Assumptions about patent expirations that were based on internet-based research (e.g. Article One Partners 2012, BioTrends 2012, DrugBank 2012a, DrugBank 2012b) were relevant for estimating the future price development (sales per DDD). In the conventional therapies segment, the patents for capecitabine (2013) and pemetrexed (2016) will then expire; in the targeted therapies segment, the patents for trastuzumab (2014) and bortezomib (2014/2015 with the exception of subcutaneous preparations) will expire.
To model the consumption and sales of new launches from 2013 to 2016, assumptions were made in order to forecast the expected number of new launches annually in the area of oncological active ingredients. The starting point was information from the European Medical Agency (EMA) about oncological active ingredients that are currently in the approval process (EMA 2012). Based on this information and the market development of active ingredients in the past, assumptions were made about the number of future market launches in the individual segments (Table 1).
The expected sales development and pricing of new active ingredients was estimated based on the market development of 28 active ingredients that were introduced between 2001 and 2012. The procedure was as follows:
1. Three to four categories were formed for each segment based on the different sales developments of active ingredients. The active ingredients were assigned to appropriate categories based on the comparability of their sales in the fourth year after market launch (or sales in previous years if they had been on the market for less than four years).
2. The ratio of the number of all active ingredients in a category to the number of all active ingredients considered in the entire segment was interpreted as the probability that a newly introduced active ingredient belongs to one of the categories. The probability per category was then multiplied by the average sales per category to determine the expected sales of the new active ingredient.
3. The assumed consumption of an average active substance within the category was formed from the quotient of sales and unweighted average price (sales per DDD) in a category. This was multiplied by the previously determined probability of belonging to a specific category, and the expected consumption of a new active ingredient was calculated in this way. The price of the new active ingredient was determined by dividing sales and consumption.

Determination of the forecast values for sales and consumption in the formed segments
Finally, based on the time series created for consumption and prices, the sales and consumption development for the segments was forecast until 2016. Epidemiological aspects, expected patient numbers, the competitive situation, patent expirations and newly introduced active ingredients were taken into account as corrective factors. The expected annual sales development per active ingredient was determined by multiplying price and consumption. Adding the forecast consumption and sales trends across all active ingredients per segment resulted in the forecast values for the segments.
Results
Overview of the development of the oncological and the entire statutory health insurance drug market
Between 2010 and 2012, sales development for oncological drugs in the statutory health insurance market was moderate (Figure 1). Overall, the market volume increased from EUR 3,298 million (AVP) in 2010 to EUR 3,547 million in 2012 (annual increase of 3.7 %). For the period from 2012 to 2016, an annual rate of increase of 9.7 % is expected for oncological drugs (Figure 1). This leads to sales of 5,145 million euros for oncological drugs dispensed on an outpatient basis in 2016. Based on the total SHI market (finished medicines and preparations) of 34,349 million, oncological drugs had a share of 10.9 % in 2012 (Häussler et al. 2013). Since lower growth rates are expected in the entire statutory health insurance system by 2016 than for the oncology submarket, its importance is increasing (Fig. 1).
Development of the segments of the oncological GKV drug market
General development
From 2013, a much more dynamic market development than in previous years can be expected, as the pharmaceutical companies have intensified their research efforts in the field of oncological diseases and numerous new products are therefore expected to be launched by 2016.
The approvals submitted to the European Medicines Agency (EMA) show that the current research focus of the pharmaceutical industry is on the drug group of protein kinase inhibitors, which belongs to the segment of targeted therapies. These are mainly supplied as finished medicinal products, often in oral dosage forms. Accordingly, the greatest increases in sales are expected in this sub-segment. Compared to 2012, sales of finished medicinal products in the targeted therapy segment are expected to more than double in 2016 (1,935 million euros), which corresponds to an annual increase of 22.8 % between 2012 and 2016.
In the segment of endocrine therapies, there is an annual increase in expenditure from 10.2 % to 804 million euros in 2016. The market for oncological preparations (targeted and conventional) is expected to grow only comparatively moderately by 3.4 % per year on the whole 2,183 million euros increase in 2016.

Detailed development of sales and consumption in the individual segments
The results show that the increase in expenditure can be attributed in particular to new active ingredients that will be introduced from 2013. These drugs will reach sales of around EUR 1,025 billion in 2016, which corresponds to a 20% share of the oncology market. For active ingredients that came onto the market by 2012, sales in 2016 are expected to amount to 4,121 million euros (compared to 2012: 3,548 million euros). This corresponds to an annual increase rate of 3.8 %. It therefore shows that 64 % of the increase in sales for oncological drugs between 2012 and 2016 can be attributed to the market launch of new active ingredients. The expected development of consumption and sales for the four segments is shown in Table 2.
Targeted therapy
Between 2010 and 2012, consumption of the 25 active ingredients in targeted therapies rose from 11.2 million to 12.9 million DDD, and sales rose from 1,648 million to 1,910 million euros. In 2012, 60 % of sales and 64 % of consumption were accounted for by four market-leading active ingredients (imatinib, trastuzumab, rituximab and bevacizumab). However, their importance in the market is expected to decrease by 2016. One reason for this is that, with the exception of bevacizumab, the leading active ingredients are expected to lose their patent protection by 2016.
Overall, an increasing sales and consumption volume in the area of targeted therapies is forecast. A sales volume of 3,150 million euros and a consumption volume of 21.5 million DDD are expected for 2016. Since the new active ingredients are predominantly tyrosine kinase inhibitors (TKI), the finished pharmaceutical market will be particularly affected by the development.
The TKIs axitinib, ruxolitinib, vandetanib and vemurafenib, which were newly introduced in 2012, play a special role here (sales in 2012: 37.2 million euros). These are expected to have sales of 304 million euros in 2016, which corresponds to a sales share of 9.6 %. The introduced PKIs are expected to have a smaller effect on consumption. This will increase from 0.32 million DDD (2012) to 2.2 million DDD (2016), which corresponds to a market share of 4.6 %.
Assuming that the active ingredients newly introduced from 2013 develop in a similar way to the new products launched in previous years, a sales share of 29 % or a consumption share of 24 % is expected for 2016. The four market-leading active ingredients to date will have a sales and consumption share of 31 % and 45 %, respectively.
Endocrine therapy
In the endocrine therapeutics segment, consumption remained largely unchanged between 2010 and 2012 (approx. 143 million DDD in 2012), while sales fell from 639 to 544 million euros. The most significant sales drivers were leuprorelin and abiraterone, which accounted for 52% of sales in 2012. The most frequently used active ingredients in 2012 were tamoxifen (24 % consumption share) and leuroproline (23 % consumption share). In contrast, the active ingredient abiraterone played a minor role with a consumption share of 0.5 %. With its high daily therapy costs (2012: 181.62 euros per DDD), its pricing is based more on new targeted therapies (147.63 euros per DDD) than on the - mostly generic - price level of other approaches to endocrine therapy ( 2.87 euros per DDD). Since the consumption of abiraterone can be expected to continue to increase, there is high sales potential due to the high daily therapy costs.
However, the development for the aromatase inhibitors anastrozole, exemestane and letrozole is declining. After patent expiry, generics for all three active ingredients have been on the market since 2011, which resulted in a decline in market shares based on sales from 49 % (2010) to 16 % (2012). However, they remain significant in terms of supply (33 % market share in segment).
Overall, sales of endocrine therapeutics will increase moderately by 2016 (804 million euros). By 2016, abiraterone will account for almost 41 % of sales and 17 % for leuprorelin. The only new active ingredient expected to be launched on the market in 2013 is enzalutamide (EMA 2012). If another active ingredient comes onto the market in 2015, as assumed in the model, then a sales share of 12 % is possible for the two new launches in 2016.
Due to the high level of saturation in the market, a constant consumption level of around 143 million DDD is expected up to 2016. The market structure will not change; tamoxifen remains the most widely consumed active ingredient. For Anastrozole, Exemestane and Letrozole, it can be assumed that generic competition will not lead to an increase in volume, as the market had already reached saturation before the introduction of the generics. Equivalent to the increase in sales, the consumption of abiraterone will also expand. A consumption share in the lower single-digit percentage range is to be expected. Consumption shares of less than one percent are expected for new launches by 2016.
Conventional therapy
Conventional active ingredients continue to play an important role even after the introduction of targeted therapies. Targeted therapies are often given in combination with conventional drugs or used as an additional line of therapy after previous treatment with conventional drugs has failed (Siddiqui et al. (2012)).
A total of 66 conventional active ingredients were considered for 2012. Between 2010 and 2012, their consumption increased from 36.4 to 39.1 million DDD, and sales increased from 992 to 1,079 million euros. The generic taxanes paclitaxel and docetaxel as well as pemetrexed, which is expected to go off patent in 2016, accounted for around 35% of sales in 2012. These active ingredients are mainly delivered as preparations. In terms of consumption, the antimetabolite fluorouracil (5-FU) with a proportion of 32 % is the active ingredient with the highest proportion among conventional cancer therapeutics. This is followed by hydroxycarbamide as the most important oral cytostatic with a consumption share of 9 %. Both active ingredients are also generic.
From 2012 to 2016, only a comparatively moderate increase in sales (annual rate of increase 2.4 %) to EUR 1,188 million is expected for the active ingredients in the segment. The moderate increase in sales is also the result of the modeled savings for generic substitution (docetaxel and temozolomide). Nevertheless, the three market leaders mentioned remain the active ingredients with the highest sales in the segment in 2016 with 36 %. Consumption will increase to an estimated 40.8 million DDD by 2016 with an annual growth of 1.1 %.
In contrast to targeted therapies, the market potential of new conventional active ingredients is rather low. The forecast assumed that six new active ingredients would come onto the market by 2016. Your sales-related market share in 2016 is expected to be around 2.5 %. The modeling does not indicate a change in market shares in consumption. The active ingredients 5-FU and hydroxycarbamide remain the most important cytostatics. New active ingredients are expected to account for almost 1 % of consumption in 2016.
discussion
This work estimates the development of oncological drugs in the outpatient statutory health insurance market between 2013 and 2016. In addition to the forecast for the entire market segment, the development of individual segments in the oncological area was discussed.
After a moderate annual increase of 3.7 % in sales in the period 2010 to 2012, a phase of increased growth in the market for oncological drugs can be expected for the next few years. An annual increase in sales of 9.7 % is forecast for the period 2012 to 2016. This is in line with other estimates, which assume annual growth rates of 6.9 % (Business Insights (2011)).
The expected market launches of new tyrosine kinase inhibitors (TKIs), which will increase sales development in the area of oncological drugs, play a special role here. However, possible short-term expenditure savings due to the expiry of patents and the associated market entry of biosimilars or generics must be viewed critically. On the one hand, the number of patent expirations by 2016 is expected to be relatively low. On the other hand, based on current experience with the introduction of biosimilars for monoclonal antibodies, weaker price competition is to be expected than with chemically defined generic active ingredients (Haustein et al. 2012).
When considering the work, limitations should be noted. The analysis was carried out on the basis of pharmacy sales prices, i.e. H. Statutory discounts from manufacturers, individual discounts based on contracts between companies and individual health insurance companies in accordance with Section 130a Paragraph 8 SGB V as well as agreed discounts within the framework of agreements on a reimbursement amount in accordance with Section 130b SGB V are not taken into account. In addition, the statements made only apply to the area of outpatient care.
As has been shown, new active ingredients in particular and the resulting expanded therapeutic regimens, for example through sequential use, drive market and expenditure development; They are responsible for 64 % of the increase in sales in the period from 2012 to 2016. The present analysis is therefore sensitive to the assumption about the number and expected market volume of the new active ingredients. Since new active ingredients in cancer therapy are usually used in addition to existing therapies (Siddiqui et al. 2012), market dynamics are likely to be similar to those in recent years. However, uncertainties remain which could weaken developments. In particular, the early benefit assessment can have an influence on the marketing of a product and result in delays in market entry or even market withdrawals.

Several conclusions can be drawn from the results.
As the second most common cause of death in Germany (Federal Statistical Office (2012)), there is a high need for therapy for cancer treatment. The increase in sales, especially in targeted therapy, is accompanied by an increase in volumes, so that the growth rate in expenditure will remain above the level of the entire statutory health insurance drug market. In particular, in the segments of targeted and endocrine therapies, sales growth due to new active ingredients can be expected in the near future.
However, it should be borne in mind that for oncological active ingredients the consumption of most active ingredients often reaches a saturation point after just a few years. The reason for this is that the life-prolonging effect of most anti-cancer drugs is limited. This means that a stable state of patient arrivals and departures is achieved in a short time. <<