They are the blockbusters in the billion-dollar pharmaceutical market of the 2020s: monoclonal antibodies. In the current top 20 of the highest-selling drugs in the world, this group of active ingredients alone occupies seven places, starting in second place, right behind the Covid vaccination from Biontech.
Therapy with monoclonal antibodies can cost six-figure sums. They are considered miracle cures and can specifically switch off tumor cells or tame the out-of-control immune systems of people with autoimmune diseases. They work according to the key-lock principle and start exactly where they are supposed to work. Some cancer patients have been cured in advanced stages of the tumor, and thanks to them, those affected by multiple sclerosis or rheumatic diseases can experience phases in which their chronic illness hardly progresses.
But monoclonal antibodies can also pose risks that are difficult to calculate. That’s what this article is about. In order to understand how greedy investors risk putting patients at risk for their profits, it is first necessary to understand their business model.
In addition to the pharmaceutical industry, some pharmacists also earn a lot of money from the billion-dollar business with monoclonal antibodies. In clean room laboratories, they mix the finished medicines, which are delivered by pharmaceutical companies in small bottles as powder or liquid concentrate, with saline solution in infusion bags. In this diluted form they run into the veins of patients. For the mixing process, which only takes a few minutes, you can often earn several hundred euros per infusion.
Such paradisiacal profit margins also attract “locusts” – investors who need to increase the assets of billionaires, insurance companies or pension funds and are hungry for double-digit returns if possible. At least four such players are currently active in outpatient cancer medicine. They were originally founded by pharmacists who weren’t actually allowed to own medical practices. This regulation goes back to the so-called Edict of Salerno from the 13th century. Apparently it was already recognized back then that the risk of cheating is great when the prescription and sale of medicines are carried out in one hand.
But thanks to a recent loophole in the law, some particularly enterprising pharmacists have been able to stock up on doctor’s offices in recent years – by first buying hospitals. One thing is enough, it can also be a dilapidated shack in order to then buy up practice locations all over Germany.
The four investors were particularly interested in the practices of cancer specialists – to whom they now sell their medications exclusively through corporate structures. The goal is apparently regional monopolies. The special pharmacies (“cyto-pharmacies”) that previously supplied the oncology practices on site and invested higher six-figure amounts in their clean rooms are being phased out and in some cases driven to ruin. In future, the cancer doctors purchased will have central laboratories supply them with ready-mixed infusions. In the case of Alanta Health Group GmbH, for example, such laboratories are located in Hamburg, Leipzig and Munich. The Germany-wide oncology network is essentially supplied via these three locations.
However, such centralized production poses risks for patients. Because monoclonal antibodies are highly sensitive proteins, they are not made for long, bumpy transport routes that can be several hundred kilometers. “Do not shake,” says the specialist information that must be followed in pharmacies. Proteins change chemically when they are exposed to mechanical stress. Anyone who has ever beaten chicken eggs knows this. The proteins in the “egg whites” have changed their structure and chemical properties; they are “denatured”. In the case of egg whites, this is desirable; with monoclonal antibodies, denaturation must be prevented using all possible measures.
The chemically modified proteins can lose their therapeutic properties and the lock and key principle no longer works. They can combine with other proteins to form larger aggregates – and these in turn can call the immune system into action. Monoclonal antibodies chemically modified in this way can provoke the body’s own defense system, which then fights the drug. Possible consequences: Loss of effectiveness, but also autoimmune reactions and allergic reactions, including life-threatening anaphylactic shocks.
All of this is well proven by laboratory and animal tests. Unfortunately, there is a lack of research into what exactly happens in the bodies of cancer patients, but the chain of evidence is convincing: In fact, “biologics” – this is the name of the upper group of protein-based drugs, which also includes monoclonal antibodies – are known to lose weight over time in effectiveness It is also not uncommon and sometimes quite early for scientists to find evidence that the body is defending itself against the medication – with the body’s own antibodies that are directed against these monoclonal antibodies.
The commercially available monoclonal antibodies react to shocks to varying degrees, as shown, for example, by a study in which the Central Laboratory of German Pharmacists e.V., the Würzburg University Hospital, the biotechnology company Leukocare and two independent cytopharmacists were involved. Two of the eleven drugs tested resulted in worrying aggregate formation. “Such results should alarm us. The potential dangers for patients must be further investigated,” says Franz Stadler, chairman of the Drug Safety Foundation, which initiated and financed the study.
However, it is difficult to prove why a drug loses its effectiveness in an individual patient. Was it really the long transport routes? Or maybe other influencing factors, for example temperature fluctuations? These can also cause damage to highly sensitive medications. Or was it just bad luck, an individual predisposition of the patient, who reacts very sensitively to these medicines?
In this unexplored territory, the profit-driven pharmacists are up to mischief, quickly centralizing the production of cancer infusions, and no one can conclusively prove that this could be to the detriment of patients.
The mechanical stress that monoclonal antibodies are exposed to while bouncing around can be significant. In a US study in which measuring sensors were placed in the transport packages of medicines, shock loads of up to 36 times the acceleration due to gravity (36 G) occurred on the roads or when loading into aircraft. A US-Canadian research team has found that transport within hospitals can also be dangerous for the proteins, for example if they are sent via pneumatic tube systems. They generally recommend not using pneumatic tubes for infusion bags with monoclonal antibodies.
An international research team under the aegis of Uppsala University Hospital discovered another risk factor: carelessness in handling the highly sensitive medicines by non-specially trained staff. For example, if a box containing vials with monoclonal antibodies falls to the floor, dangerous air bubbles could form in it, which could lead to protein denaturation. Such infusions would then have to be inspected by experts – but this only rarely happens, according to the scientists.
A question that seems obvious here: How would German parcel carriers who work on behalf of an investor-run company behave if a container of medicines worth four or even five-digit amounts were dropped on them? What if no one saw it?
Scientific interest in researching the influence of long transport routes on cancer infusions is limited, also because it is a specifically German phenomenon – created by the legal loophole through which large pharmaceutical companies in this country came to own doctors’ practices. Pharmacist Klaus Meier, President of the pharmaceutical-oncology umbrella organization “European Society of Oncology Pharmacy” (ESOP), knows this. For example, when he spoke to his vice president from France about it, he said to him: “Klaus, you know we don’t have this problem at all.” Because in France, infusion solutions are manufactured where they are then administered.
The star asked the European Medicines Agency (EMA) what it thinks about the practice that is spreading in Germany. She acts surprised. Such an approach seems to contradict the guidelines of the EMA Committee for Human Medicines, according to a spokesman for the authority: “The solution for the infusion should be prepared at the site of administration.” And as quickly as possible.
In Germany, the Paul Ehrlich Institute (PEI) monitors the safety of medicines. But the authority’s responsibility ends with the bottles containing the active ingredient concentrates manufactured by pharmaceutical companies – i.e. before they are diluted in the clean rooms of pharmacies and investor-run corporations. “Monitoring the transport routes (errors during transport, incorrect cold chain or storage) is not the responsibility of the Paul Ehrlich Institute,” the head of the authority, Klaus Cichutek, tells stern via the press office. The Medicines Act stipulates that the state authorities are responsible. Inquire at the Bavarian State Office for Health and Food Safety (LGL) – i.e. in a federal state where investors are very active. “With regard to patient-specific infusion solutions, which are prepared in pharmacies, for example, the LGL has not received any orders for investigations regarding particles in the past ten years.”
So no one seems to be responsible for a safety problem that could potentially endanger many cancer patients. The authorities give the impression that there is no interest in further researching this problem, as the PEI emphasized when asked. “From the perspective of the Paul Ehrlich Institute, the particle formation of drugs containing antibodies is known and is also adequately addressed by the marketing authorization holder.” A view that pharmacist Kerstin Bornemann, deputy chairwoman of the Oncological Pharmacy Working Group at the German Cancer Society, would definitely not agree with. “The manufacturers’ approvals have not been checked for the transport routes of the infusion bags with the mixed active ingredient.”
The silence of cancer doctors on this explosive topic is puzzling. For several weeks, stern tried to get a statement from the German Society for Hematology and Oncology (DGHO). It is the umbrella organization of those who handle the cancer infusions delivered from the pharmacy every day – including, of course, oncologists who work closely with the investor-run companies. Perhaps they have not been able to agree on a common stance on the issue and prefer to remain silent.
In any case, Wolf-Dieter Ludwig, long-time chairman of the German medical profession’s drug commission and himself a cancer doctor, has clear words: “A responsible oncologist should insist that monoclonal antibodies are only used if they were manufactured locally in a pharmacy and are therefore administered promptly In his opinion, this should apply as long as the influence of transport routes on their effectiveness and safety has not been sufficiently investigated.
In recent years, health experts and legal scholars have been working on the big question of whether the hustle and bustle of locusts in the German health sector is generally dangerous for patients. Are incorrect diagnoses made in order to generate more income, are unnecessary treatments given, and are people with illnesses that are of little profit turned away? There is currently no evidence of such suspicions, but it is also difficult to investigate – data protection and medical confidentiality prevent access to patient data.
So far, the only thing that has emerged is that investor-run practices billed more cleverly and, depending on the specialist area, generated up to 25 percent higher income. Although this would be harmful to the national economy, it would not necessarily be dangerous for those treated. However, this text provides evidence that the potential harm to patients’ health is at least accepted with approval – in the interest of profit.
As long as there are so many unanswered questions, it would be up to patients and patients themselves to ask their doctors: “Where exactly does my infusion come from?” A question, however, that requires a lot of courage, the relationship of trust is at stake.
