>> The basic patent protection for a total of 18 pharmaceutical substances will expire in Germany in 2020 (as of January 2020; source: patent database SHARK, INSIGHT Health). The substances are used, among other things, to treat rheumatoid arthritis, multiple sclerosis, in oncology and pain treatment. This is also reflected in Figure 1, in which the substances are distributed into the corresponding ATC1 classes. This means that three substances in the class of systemic anti-infectives lose their exclusivity, while there are four each in the L and N markets. This makes it possible for new, cost-effective medicines to enter the market in the form of generics or biosimilars. However, it cannot be predicted when and whether manufacturers will bring copycat products onto the market in Germany.
1.13 billion euros in 2020
released for the generic market
In the MAT (Moving Annual Total) November 2019, the total of 18 pharmaceutical substances that are out of patent protection this year represent a sales volume (according to ApU, selling price for pharmaceutical companies) of around 1.13 billion euros (source: outpatient GKV prescriptions). for finished medicinal products and preparations; INSIGHT Health). If this turnover is calculated according to ATC1 classes
structured, there is a clear focus on the ATC1 classes L (antineoplastics and immunomodulators) and N (nervous system). Both classes together, which include a total of eight substances, account for around 70 percent of the sales volume. The systemic anti-infectives (ATC1 class J) are also represented by three substances, although their relevance to sales is negligible in relation to them. An additional look at the substances with the highest sales yields a much clearer picture (see Fig. 2).
This year, copycat products for four biopharmaceuticals are expected to be available, along with a bivalent vaccine against human papillomavirus (HPV). All four biologicals are in the top 5 in terms of sales strength and achieved statutory health insurance sales of approximately 833 million euros (according to ApU) in MAT November 2019. This is almost three times as much as the remaining 13 non-genetically engineered substances combined. This clear weighting suggests that biosimilars will be the focus again this year. As a result, further shifts in sales in the pharmaceutical industry are to be expected. In addition to the classic generic manufacturers, the biosimilar market also opens up new fields of activity for companies from outside the industry. In addition, new business units have been established at various original manufacturers in recent years for the market entry of their own biosimilars.
The highest-selling substances
Eculizumab, with the second highest sales share of 17.4 percent, is a monoclonal antibody for the treatment of paroxysmal nocturnal hemoglobinuria, a very rare blood disease in which erythrocytes are destroyed by the immune system. In MAT November 2019, more than 41 thousand packs of eculizumab were prescribed in the outpatient statutory health insurance market, primarily through internists and outpatient clinics.
The monoclonal antibody tocilizumab, which is directed against the interleukin-6 receptor, had a sales share of 15.6 percent in the same period under review with a statutory health insurance prescription volume of almost 80 thousand packs. The anti-inflammatory and immunosuppressive effects of the substance are primarily used to treat rheumatoid arthritis, including the juvenile form. With 11.3 percent, tapentadol is the only non-genetically engineered drug in the top 5 ranking. Finally, Natalizumab should be mentioned at this point, which is used for the highly active form of relapsing-remitting multiple sclerosis and for Crohn's disease and is still one of the top 5 active ingredients with a sales share of almost 11 percent.
Bevacizumab: from June
Biosimilar competition
Among the substances whose patent expires this year is the cytostatic drug bevacizumab. The biological was the first angiogenesis inhibitor that reduces the formation of blood vessels and thus the supply of blood and nutrients to the tumor through a targeted inhibition of VEGF (Vascular Endothelial Growth Factor). The monoclonal antibody is used in combination with chemotherapy in numerous tumor diseases: breast carcinoma, colon or rectal carcinoma, non-small cell lung carcinoma, renal cell carcinoma as well as ovarian carcinoma, fallopian tube carcinoma, cervical carcinoma and primary peritoneal carcinoma. In MAT November 2019, bevacizumab is one of the top 10 substances with the highest sales in the entire GKV market with sales of more than 334 million euros (according to ApU) (source: outpatient GKV prescriptions for finished drugs and preparations; INSIGHT Health). At the beginning of 2018, a biosimilar from Amgen and around a year later another from Pfizer were approved by the EMA (European Medicines Agency). Numerous other manufacturers are in the starting blocks when the patent expires in mid-June. Especially since the PUMA (Pediatric Use Marketing Authorization) for bevacizumab had already delayed the entry of the biosimilar by six months. For example, Samsung's biosimilar Bioepis, a joint venture between Samsung Biologics and Biogen, is very advanced in the pipeline. With the patent expiry of the TNF-alpha inhibitor adalimumab in October 2018, the manufacturer had already shown that it was ready to intensively address competition with the old original, but also with biosimilar competitors, with an aggressive pricing strategy for the biosimilar. Something similar can be expected for bevacizumab. Furthermore, experiences with the two oncological drugs rituximab and trastuzumab show that biosimilars are also quickly becoming part of the care in oncology. For rituximab (first biosimilar in May 2017), the biosimilar quota based on DDD (defined daily dose) is already 81 percent in Q3/2019, and for trastuzumab (first biosimilar in May 2018) it is 72 percent. As of November 2019, no discount agreements have been concluded for bevacizumab. Only IKK classic has advertised an open house contract, which has not yet been fulfilled. The share of sales from imports in MAT November 2019 is well over 2 percent (sources: GKV billing data for finished drugs and preparations and tender alert, INSIGHT Health). There is no question that neither discount agreements nor imports will determine competition in the second half of the year. Rather, it's about how many biosimilars enter the German market at what point in time and, of course, what price reductions and discount contract strategies the new players and, last but not least, the originator are pursuing.
Tapentadol: non-genetically engineered drug in top 5
In terms of sales share, the opioid analgesic tapentadol is in fourth place among the pharmaceutical substances coming off patent in 2020. Among the top 5 substances, it is the only non-genetically engineered drug. The substance, which currently has basic patent protection, is used against moderate to severe pain and is subject to the Narcotics Act. Tapentadol was the first new entity in these indications in 25 years when it was launched in late 2010, and has remained the last since then. Due to the already generic competitive environment, consisting of morphine, oxycodone, fentanyl and hydromorphone, the discount rate for tapentadol in MAT November 2019 is around 80 percent (source: GKV billing data, INSIGHT Health). The possible entry of generic imitators for the dosage forms that are losing patent protection will not so much increase the discount rate as it will put pressure on the official list price and the amount of discounts granted. It will be interesting to see whether tapentadol, analogous to the three opioid analgesics buprenorphine, hydromorphone and oxycodone, is included in the substitution exclusion list due to its narrow therapeutic range. This would possibly reduce the pressure to switch to a generic.
outlook
The overview of patent expirations shows that there will also be worthwhile sales potential for imitators in 2020, particularly in the biologicals sector. Similar to previous years, summarized in the so-called second wave, patients in rheumatology and oncology in particular benefit from market penetration with biosimilars. In 2021, another five biopharmaceuticals are expected to lose their market exclusivity (e.g. interferon beta-1a). Together with the six biologics whose patent protection expires in 2022, the focus is once again on biologicals. Summarized as the third wave of ophthalmology and immunology, biosimilars are likely to be available to patients that are used to treat neovascular age-related macular degeneration and other eye diseases as well as for anti-inflammatory therapy. <<
Authors: Kathrin Pieloth,
Esther Zöllner, Christian Luley*
* INSIGHT Health ([email protected]); Literature from the authors
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