We already have the first Polish biosimilars. “This is hope for patients around the world”

Katarzyna Pinkosz, Wprost: We are still waiting for innovative new drugs designed by Polish scientists to be created in Poland. Will Polpharma Biologics produce such drugs? Two biosimilar drugs developed by the company are already on the market.

Adriana Kiędzierska-Mencfeld: At Polpharma Biologics, we develop and manufacture biosimilars. However, we do not develop innovative drugs, i.e. original biological drugs. Perhaps this strategy will change in the future. However, biosimilars are our priority now. In this way, we want to increase the availability of biological therapies for patients. Another company from our ownership group, JJP Biologics, is responsible for the development of innovative biological drugs.

Both original drugs and generics or biosimilars are needed by patients. But first, let’s explain what a biological drug is, how it differs from a “chemical” one, and what is a biosimilar?

The most common type of drugs that are currently administered to patients are traditional, chemical drugs. Unlike biological drugs, they have a simpler chemical structure, predictable pharmacokinetic and pharmacodynamic properties. What’s more, they are stable, relatively inexpensive, and easily accessible. Biological drugs work with great precision. They are created in living cells that are grown in the laboratory. Similarly to gene or cell therapies, they are considered drugs of the future that will revolutionize medicine because they give hope for curing or stopping previously incurable diseases.

One type of biological drugs are monoclonal antibodies, which enable precise therapies for certain chronic diseases. At Polpharma Biologics, we deal with biosimilar drugs. They are also biological drugs. Biosimilar medicines are biological medicines. The difference in nomenclature is a market issue that helps understand which drug was available first. Therefore, it is commonly accepted that an original biological drug is simply called a biological drug, and subsequent biological drugs based on the same active substance intended for the treatment of the same disease are called biosimilar drugs.

So from the patient’s point of view, the production of a biosimilar drug is no less important than the production of a biological drug, because more people simply have a chance for treatment?

We need both biosimilar and innovative medicines. Biosimilar drugs are hope for all of us that modern medicines will be more available. They are definitely cheaper and as effective as reference drugs (called innovative). Patients often do not have access to therapy due to its high costs. Biosimilar drugs lower this price barrier. However, we need innovative drugs, if only to increase the effectiveness of treatment, including diseases that are currently incurable.

Okay, but where does the choice come from that we want to develop and produce this particular molecule and not another? How does the idea come about that this particular drug is worth producing?

The entire process of selecting a molecule is very complicated and includes a number of variables. One of them is what diseases or groups of diseases we want to cover in the selection, but also the fit to the technology we have developed. There are several ways to produce biologics. They can be, among others: produce in bacterial cells or in mammalian cells. We use both options. Through genetic engineering methods, these cells can be changed to produce large amounts of a specific product. In our case, these are monoclonal antibodies or their fragments. We can therefore use methods that are based on our technology that we already have or one that will only need to be slightly modified. I must also add that the development and production time of a biosimilar drug is 10-12 years. The decision must therefore be well thought out.

So the choice is very important?

Yes, some smaller companies may even disappear from the market after making such a poor choice.

Many biological drugs are used in oncological diseases. The interest of companies in these molecules is much greater. Our interest so far has been directed at autoimmune diseases, which are also a major civilizational challenge. One such disease is multiple sclerosis.

Why does it take 10-12 years to develop a biosimilar drug, when – one could say – we already have a certain model (reference drug) that only needs to be reproduced?

When choosing a product, we know what molecule (the so-called active substance) constitutes the original medicine (the so-called reference medicine). In the next stages, we need to analyze what cells can produce this drug. The choice is not easy. We need to find those that produce large amounts of the active substance as similar as possible to the original (reference drug). We look at how product specifications are changing in the market to determine the range of product variability. The choice of cell line is crucial, and then the processes of selecting a specific cell, the so-called maple.

Next, we check the conditions in which the cell is grown. The choice of the cell medium, which provides the cells with the necessary nutrients, is also important. Colloquially, we can say that it is the “food” for the cells. It determines not only the growth of the cell, but also the mechanisms triggered in it. This is a complicated, long-term and important process. Then we have to determine the temperature, culture time, pH, oxygenation – many factors are important here.

Analytical methods (e.g. determination of concentration or activity) are being developed in parallel. There are over forty of them. They allow us to better characterize (describe and determine) the features of the molecule and make sure that it is actually biosimilar. The next process is its purification. We finish this process by having an active substance. Another very important stage is the development of the formulation, i.e. the solution in which the product is stable and can be administered to the patient. These can be, for example, filled syringes with needles, vials with the drug or powder for preparing the solution. Patenting the formulation is often carried out in parallel with patenting the molecule. This is the stage at which we can differ from the original drug – choose the formulation so that, for example, the biosimilar drug is more stable than the original.

In the case of biological drugs, we are not able to produce several batches of drugs in one day. This time is extended because we need more time for the cells to grow so that they are able to produce the right amount of the product. We can only accelerate the production of the drug to a certain point, then we have to wait for the cells to divide. The complexity of the production process and the time of this process also means that the costs of biosimilar drugs are higher than those of chemical drugs.

Are scientists working on all this?

Yes. You need to carefully design the gene, select appropriate cell lines, modify them, and select cells from the pool of those that produce this drug. It all sounds very simple, but in practice the time from developing a molecule to receiving approval for distribution by the most important international regulatory agencies is about 10-12 years. Scientists, engineers and specialists work at each of these stages.

Why can’t a biosimilar drug perform better than the original drug?

If it were a drug with better effects, it would not be biosimilar. It would simply be a new drug. Our goal is to increase access to treatment for patients who need it the most. In the case of biosimilars, the clinical trial process is shorter because the effects of the drug are already well known. We can say that the original drug paves the way in this regard and there is no need to go through the second stage of clinical trials. Only the first and third are required. This significantly shortens the time and lowers the costs, and thus more patients have a chance for this drug.

We have established that the process of creating a biological drug is complicated. Hence the price is higher than in the case of chemical drugs. Biosimilar drugs are a solution in this regard. However, there is still some concern, especially among patients receiving original biological drugs, related to the transition to biosimilar drugs. Is there a reason for such concerns?

The regulations that determine whether a drug is approved for sale are extremely restrictive. The active molecule of a biosimilar drug must be described much more precisely and characterized much more than the molecule of the original drug. Before we even move on to clinical trials, we must prove that our molecule is in fact similar to the original drug and the variability between batches is minimal.

Regulatory institutions are placing much higher demands on biosimilars, because much more is already known, for example, about the adverse effects of the original drug. I would even go so far as to say that biosimilars are much safer, because their variability is much lower.

So, to some extent, biosimilar drugs may be slightly better?

In terms of performance, no. But in terms of batch-to-batch variability, yes.

Two Polpharma Biologics molecules are already in production. Will there be more?

Last year, we obtained approval from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) to distribute our first biosimilar drug developed and manufactured from scratch in laboratories in Poland – at Polpharma Biologics. This is a biosimilar natalizumab used in the treatment of multiple sclerosis. In turn, two years ago, the same institutions issued approval to distribute a biosimilar ranibizumab used in the treatment of the wet form of age-related macular degeneration.

We are working intensively on new biosimilar drugs. They are at different stages of development. The most advanced work is ongoing on biosimilar vedolizumab, which is used in the treatment of inflammatory bowel diseases, e.g. in Crohn’s disease. It has already completed the first phase of clinical trials.

These achievements would not be possible without the excellent team we create at Polpharma Biologics. This is thanks to Polish and foreign scientists. Together we gather knowledge and develop the domestic biotechnology sector. Today we can boast of a great team, qualified staff of scientists and achievements on the global market. We built everything from scratch.

Adriana Kiędzierska-Mencfeld is the director of Polpharma Biologics in Warsaw-Duchnice, a member of the management board of Polpharma Biologics SA