Cost-savings and potential cost-savings through the distribution of generic antiretroviral drugs within the statutory health insurance market of Germany between January 2017 and June 2019

Combined antiretroviral therapy (cART) has substantially reduced the morbidity and mortality of the growing number of people infected with human immunodeficiency virus (HIV) [1‐3]. HIV treatment in Germany has been very successful, with 93% of treated persons virally suppressed [4]. Therefore, cART has been the standard of care since its introduction in the mid-1990s and became the highest direct cost of HIV treatment in Germany, accounting for more than 85% of costs [5‐7]. While the total expenditures for all drugs within the statutory health insurance (SHI) of Germany amounted to approximately 39 billion € in 2018 [8], the expenditures on antiretroviral drugs (ARV) for patients with HIV, representing less than 1% of the total health insured community of Germany, amounted to approximately 1.3 billion € (≈3% of total drug expenditures) [9, 10].

Important regulations have been introduced by the German legislation with the aim of curbing prices of patented drugs as well as the increasing expenditures on pharmaceuticals incurred by sickness funds. These include, firstly, the German Act of reinforcing SHI competition that was passed in 2007 in order to facilitate the use of generic drugs after the patent expiration of branded drugs which is usually 20 years after the filings of patent applications [11‐14]. Secondly, the Act on the Reform of the Market for Medical Products, passed in 2011, which obligated manufacturers to demonstrate the additional therapeutic benefit of newly developed pharmaceuticals. This additional benefit is the basis for the price negotiations between the Federal Association of Statutory Health Insurance Funds and pharmaceutical manufacturers [15, 16]. Furthermore, as per the Social Code Book, German sickness funds are permitted to negotiate discount agreements with drug manufacturers [17].

Regardless of economic interests, the distribution of ARV must adhere to current treatment guidelines that recommend a combination of three drug classes for the initiation of the HIV therapy, preferably as a single-tablet regimen (STR) [18]. Generic ARV started to gain popularity in Germany between 2011 and 2013, starting with zidovudine, and followed by lamivudine, nevirapine and efavirenz [19]. The initial proportion of generic ARV in 2014 was rather small with 3.1% of total ARV distribution. When assuming the maximum possible use of generic ARV, the total potential cost-saving would have been 8% [20]. However, according to current treatment guidelines, most of these substances are no longer recommended for the initiation of the antiretroviral therapy, causing their market share to decline [5, 18]. In contrast, the launch of generic tenofovir disoproxil/emtricitabine (TDF/FTC) in August 2017 brought about a transformative change to the market of generic prescriptions. This was driven by its approval for pre-exposure prophylaxis, leading to unique price reduction of more than 90% [21], whereas price reductions for generic drugs within the German ARV market usually range between 10 and 40% [22]. Subsequently, a high budget impact was expected, as more than 70% of the cART regimens in Germany were based on TDF/FTC in 2017 [23].

Since almost one-third of the available ARV lost their patent protections, the debate about cost-saving through generic replacements is still ongoing [5, 24‐27]. This entails the split of newer and recommended STR into their single substance partners, irrespective of the medical indication for a change of treatment and accepting the possible consequences of higher pill burdens for patients [28‐30].

In this study, our aim was to firstly describe the current ARV market within the German SHI. Secondly, we aimed to determine the cost-savings achieved through the distribution of generic drugs, focusing particularly on TDF/FTC. Our third aim was to determine the potential cost-savings that could be achieved additionally when assuming the maximum possible use of generic ARV. This includes the splitting of STR, replacing all substance partners with generic ones and replacing the patented drug tenofovir alafenamide/emtricitabine (TAF/FTC) with generic TDF/FTC.

From 1/2017 to 2/2019, the DDD of generic ARV increased nearly five-fold and their revenue by more than four-fold (Fig. 1 A and B). The DDD of ARV with an expired patent, on the other hand, decreased continuously, while patented ARV showed a sharp decrease for the first time in 2019. In total, DDD and revenue decreased stepwise by one-sixth and by almost one-fourth, respectively.

The total cost-saving through the distribution of generic ARV showed a steep increase from 1.2 million € (< 1% of total revenues) in 1/2017 to 17.3 million € (10% of total revenues) in 2/2019 (Fig. 2). TDF/FTC leveled off at about 70% from 4/2017 until 4/2018, and the decline in its cost-savings thereafter may be attributed to the launch of generic darunavir (DRV) in 1/2019 (Table 1). A detailed overview of the cost-savings achieved by each generic ARV can be found in Supplementary Table S2.

Generic TDF/FTC also has a pivotal influence on the course of potential cost-savings, particular for the splitting and generic replacement of tenofovir disoproxil/emtricitabine/rilpivirine and tenofovir disoproxil/emtricitabine/efavirenz (Fig. 3) as well as for TAF/FTC and tenofovir alafenamide/emtricitabine/rilpivirine (Fig. 4). However, maximizing generic substitution would not have led consistently into potential cost-savings and overall downward trends have been observed since mid-2018. A detailed overview of the potential cost-savings of each ARV can be found in Supplementary Tables S3, S4, S5. Accordingly, the combination of potential cost-savings through a maximum possible use of generic ARV increased to 38.3 million € in 2/2018 (18% of total revenues) and then decreased to 19.2 million € in 2/2019 (11% of total revenues).

Using data of ARV reimbursed by the SHI, this study shows the increasing influence of generic ARV in Germany, accounting for almost one-fourth of the total ARV market in mid-2019. In particular, the unique price reductions for generic TDF/FTC substantially affected the course of cost-savings and potential cost-savings between January 2017 and June 2019. Assuming the maximum possible use of generic ARV, the splitting of STR and replacing TAF/FTC with generic TDF/FTC specifically, revealed substantial potential cost-savings.

This paper has several limitations. Firstly, the dataset used did not allow access to the private health insurance sector which accounted for approximately 11,5% of the total health insured community of Germany [10]. This may have given a more complete picture.

Secondly, our assumption to determine the potential cost-savings was not applicable for ARV containing elvitegravir, bictegravir and lopinavir, since these substance partners are only available as a fixed combination preparation without generic substitute [18]. Since single TDF, assumed for the treatment of hepatitis B, was excluded, the split of tenofovir disoproxile/lamivudine/doravirine was also not considered (Table 1) [35].

Thirdly, we were informed that some pharmacies refused to transfer their data to the responsible billing centres in the health insurance regions of Berlin, North Rhine-Westphalia and Baden-Wuerttemberg at the end of 2018. This may have resulted in an additional decrease of total DDD, estimated at about 5–7%, in 2019.

Generic drugs are progressively distributed in the German ARV market and ensure increasing cost-savings. Unique price reductions of generic TDF/FTC have played a pivotal role for both the cost-savings and potential cost-savings. However, as mentioned before, pursuing the maximum possible use of generic ARV should not fail to adhere to the treatment guidelines and consider the medical requirements for a change in treatment.