Out-Law Analysis | 19 Aug 2020 | 3:51 pm | 6 min. read
Collaboration with others can not only help biosimilar manufacturers develop their products faster but also get those products to market more effectively in a way that overcomes patent risks and other barriers to take-up, such as patient and clinician confidence in the product.
Biosimilars are medicines that seek to compete with originator biologic products. Biologics contain active substances derived from biological sources and are often large, complex molecules, such as antibodies.
Biologics are some of the most profitable and widely prescribed medicines. Adalimumab, used for the treatment of a number of conditions including rheumatoid arthritis and Crohn's disease, is currently the world's best-selling prescription drug. It is therefore not surprising that the biosimilar market in Europe is highly competitive.
Experience in Europe so far suggests that biosimilars are typically around 20% to 30% less expensive than originator products. Biosimilars therefore offer considerable cost savings to public health systems. As more originator products come 'off patent' – i.e. the patent which protects the product itself expires – biosimilar manufacturers will be seeking innovative ways to clear the path from any secondary patents, which often protect dosage regimes and methods for delivering the medicine, and achieve good market penetration.
The European Medicines agency (EMA) is responsible for authorising and monitoring biosimilar medicines in the EU. While approval of biosimilars is far more progressed in Europe compared with the US – over 60 biosimilar medicines have been approved in Europe to date, compared with only 28 in the US – there are considerable differences in biosimilar uptake between European countries.
There is no singular reason for this, but there are a number of general, as well as local factors which play a part. One of the main reasons for the wide variation in adoption of biosimilars is that individual European countries take different approaches in how they procure medicines and negotiate prices. This may result in biosimilar medicines being more readily available and priced more favourably in one jurisdiction compared with its neighbours.
Pricing is a central issue. Greater competition is likely to drive down prices. When the patent exclusivity for adalimumab expired in October 2018, biosimilars entered the market shortly after and made a huge impact. By November 2018, it had been reported that AbbVie, the originator company, was offering discounts of up to 80% in parts of Europe to account for the increased competition. The more competition there is in one country or region, the more that prices are driven down, leading to increased uptake of that particular medicine.
Another factor is that the EMA does not regulate therapeutic interchangeability or substitution of an originator medicinal product by a biosimilar. It is instead left to individual EU member states and their national health authorities – such as the National Institute for Health and Care Excellence, NICE, in England – to determine whether a biosimilar should be prescribed instead of the originator product. This leads to a wide variation in take up of individual biosimilar medicines between countries.
Clinical practices and patient confidence, both of which are major drivers in the uptake of biosimilar medicines, also play a part. There are different clinical practices, including differing levels of confidence in the biosimilar products, as opposed to the originator biologic medicines. Patient confidence in the use of and compliance with prescribed medicines is vital, and is linked with the readiness of clinicians to prescribe biosimilar medicines. Patients are sometimes reluctant to accept a substitution to the biologic medicine with which they are familiar.
Patient confidence is also an issue in relation to the method of drug delivery. Biosimilar medicines are usually delivered by a device such as an auto-injector or prefilled syringe device, and are often administered by the patient themselves. Patients need to be confident that the delivery method is reliable, easy to use, convenient and that pain is minimised otherwise they can be put off the product. Design of the delivery method is therefore crucial, and ensuring that patients are familiar with the design can help in enabling patients to switch from one treatment to another.
Given these pressures, and the highly competitive market, it is essential that manufacturers remain competitive. Agile strategies with regards to market entry are paramount.
Engaging in joint venture and strategic partnerships can help biosimilar manufacturers get their product successfully to market. A number of businesses in the biosimilar industry have entered into joint ventures and co-development arrangements already. This is a particularly useful strategy in countries with high commercial potential for biosimilars, since it is these markets that will attract intense competition. It is fundamental for companies to get an edge and be the first to market.
Product development can be expedited from gaining both local and foreign expertise, access to development platforms and funding for research and clinical trials
The enormous potential of the biosimilars market has led to a number of recent, high profile collaborations. Samsung Biologics and Biogen entered into a joint venture, forming Samsung Bioepis, which has launched biosimilars of adalimumab, infliximab, etanercept and trastuzumab in Europe, with others in the pipeline. It has also entered into a number of commercialisation partnerships. Formycon and Aristo Pharma entered into a joint venture for the development of a biosimilar for ustekinumab, a product used to treat psoriasis among other conditions. Fujifilm Kyowa Kirin Biologics and AstraZeneca's joint venture, Centus Biotherapeutics, has been operational since 2015 and currently has a biosimilar for anti-cancer product bevacizumab in the pipeline.
Collaborations between larger, multinational companies offer a number of advantages, many of which are vital for successful market entry and sustainability in such a competitive market. Product development can be expedited from gaining both local and foreign expertise, access to development platforms and funding for research and clinical trials.
However, taking the developed product to market is just as important, and collaborating with a large biopharmaceutical manufacturer enables access to established manufacturing facilities. This can include the outsourcing of activities such as cell line development, manufacture of biologics and biosimilars, process scaling, and any required technology transfer. Collaboration with larger multinationals also permits access to product distribution channels and strong marketing networks. It also provides the opportunity to lobby governments and regulatory authorities to promote approval of the biosimilars as a substitute to originator biologics.
There are longer term benefits from collaborations too. They can make it easier to tender for any future biosimilar production projects within the country, which can offer earlier and more efficient product development and market penetration. In a sizeable market such as Europe, which has a significant country-level diversity in terms of healthcare policies and market dynamics, access to local knowledge on the ground obtained through such collaborations can also prove invaluable.
Underpinning these collaborations is the expectation that, as many biologics medicines come off patent over the next few years, the market for biosimilars is likely to expand considerably. In the face of increasing competition from a number of biosimilar manufacturers, the need to maintain a competitive edge, for both originators and competing biosimilar manufacturers, is going to be greater than ever.
Biologics and biosimilars present specific challenges with respect to formulation development due to the nature of the medicine. Biosimilar manufacturers should check whether any aspect of their product could be protected in its own right by a patent. We have seen a number of biosimilar manufacturers filing and asserting patents in Europe covering formulation, delivery devices or dosage regimes.
The design of a drug delivery device has become a crucial consideration. When switching to a new biosimilar, patients may experience difficulties if they are using a different device that is unfamiliar. Improvements in design which lead to ease of use may be an important factor in the uptake of the biosimilar.
Further collaboration, namely that between pharma and device manufacturers, is therefore essential to developing and bringing a successful combination product to market. Most large pharma companies employ dedicated device teams who develop a close working relationship with the device suppliers.
There will be competition from the innovators that will shape the market too. Innovators have used various strategies to remain a step ahead of biosimilar competition, including changing how products are administered and developing a ‘biobetter’ which offers improvements over the originator biologic. These strategies may result in the originator companies obtaining new patents or other intellectual property rights which biosimilar companies may then need to work around. Novel formulations in particular have the potential to be of commercial importance. An example of this can be seen with how the development of a citrate-free formulation of Humira – the brand name for the originator biologic adalimumab – helped reduce the level of pain to patients for needle injections of the medicine.
In an intensely competitive environment, agile go-to-market strategies are essential. By engaging in joint ventures and commercial partnerships, many biosimilar manufacturers have shown how effective market access can be achieved.