A Two Million Injection What Happens to Spinal Muscular Atrophy Medicines

The United States has approved the world’s third drug for the treatment of spinal muscular atrophy. On the market, it will have to compete with the most expensive drug in the world, a dose of which costs two million dollars. Let’s see where these prices come from and what made the new drug cheaper.

In early August 2020, a health experts commission approved the inclusion of a drug for spinal muscular atrophy in the List of Essential and Essential Medicines. The families of patients began to celebrate the victory – this would mean that the price of the drug would drop by a quarter.

Biotechnology has reached a new level: modern drugs cannot be afforded not only by individuals but also by entire states. What does this happen? And what technology will have to be invented to stop this rise in prices?

The devil in numbers

How expensive can drugs be? This question was raised again in May 2019, when Novartis announced the price of its new gene therapy drug for spinal muscular atrophy. The company sells the ability to supply a patient’s neurons with a “healthy” copy of the SMN1 gene and thereby save these cells from death, and the company sells the owner from a wheelchair for $2.125 million. Nobody has ever asked for that much per dose of medicine.

Previously, the palm of this primacy belonged to another gene therapy drug, Glibera, which helped people with lipoprotein lipase deficiency, in other words, taught the cells of their vessels and muscles to capture lipids from the bloodstream. It was worth about a million dollars and lasted in the market from 2012 to 2017. For many patients, this amount turned out to be unaffordable, and during the entire existence of the drug, only three dozen patients received it, most of them were free of charge, as part of clinical trials. In 2017, the manufacturing company removed the drug from production – the project never paid off.

Nevertheless, two years later, Novartis was not afraid to ask for twice the amount of Zolgensma for its drug. And now, in the list of expensive drugs, it is in the lead by several times. Strictly speaking, it is difficult even to calculate who should be next in this rating – other drugs can claim second place only if you add up the cost of all doses that a patient needs during the year. But even with this calculation, the cost of the most expensive drugs turns out to be no more than a million dollars a year. What makes Novartis raise the bar even higher? And why does the company expect its record holder to pay off?

Devil’s advocate

This is where brutal strategic calculation comes in. The money that the patient and his family give for the medicine should cover not only the cost of producing ten milliliters of healing liquid and the work of the nurse who gives the injection. They have to recoup the cost of developing this fluid – and the development company, which was later bought by Novartis, declared expenses at $ 60 million back in 2017. To “beat off” only them, the pharmaceutical company needs to sell 180 injections.

In addition, this money should offset its costs of developing all other drugs for the same disease that have failed to cross the threshold of clinical trials and enter the market. And companies usually have a lot of such failed projects – in total, they make up at least 80 percent of all those who enter the race for approval.

Finally, there must be something for the future: in addition to spinal muscular atrophy, there are many genetic diseases in the world, and it is logical to expect that a company, having successfully coped with one of them, will apply its developments to treat others. And as always, four out of five will fall off halfway before reaching the finish line.

The creators of “Glibera” for a million dollars did not manage to make money even to “beat back” the development of the drug for three years of sales. This is understandable: about 1 person per million suffers from hereditary lipoprotein lipase deficiency, which is about seven thousand customers all over the world. There were not enough people among them with a million dollars for therapy. Zolgensma has two orders of magnitude more potential buyers: one out of 10,000 children is born with spinal muscular atrophy. However, many of them do not live to see therapy, and others do not have money for any medical care.

However, there is another consideration. Drug manufacturers set prices because they know people will be willing to pay. When treatment is vital, people are even ready to take loans to cover medical bills.  Many Americans still have to take payday loans to afford expensive medical treatment. The popularity of payday loans is due to instant funding and simple eligibility criteria. For example, to get accepted for online loans in Georgia, you only need to have some kind of identity verification, a steady income, and a bank account in your name. The money can be spent on anything, including the purchase of medication.

According to a spokesman for the US Institute of Clinical and Economic Expertise, by the time Zolgensma was approved, insurance companies were ready to cover any costs of spinal muscular atrophy treatment. It is possible to speculate for a long time about where this determination came from and whether it is worth saying thanks to charitable foundations that raise a fuss around serious illnesses (and in this way they allegedly raise the willingness of insurance corporations to pay), or scientific journalists who paint in paints the hardships of developing new drugs (and so they show the reasons not to reduce the price). But the fact is clear: while experts complain that the gradual increase in drug prices is boiling healthcare alive, insurance companies are allocating money, and patients are getting their injections.

Conversations about whether a medicine can cost so much rests on speculations about the value of human life. Children with spinal muscular atrophy of the first, most severe, type rarely live up to two years without treatment. In rare cases, when the disease is mild, patients manage to survive to adulthood – but with the help of a ventilator and are almost completely paralyzed. In such a situation, the benefit from the drug is measured not in individual years, but in whole lives.

The cost of human life can be calculated formally, relying on the benefits that each citizen brings to his country on average, as well as the subjective assessments of people, that is, the amounts that they are willing to pay for the safety of their existence. So, the American Institute of Clinical and Environmental Expertise gives figures of 100-150 thousand dollars per year of high-quality (that is, relatively healthy and fulfilling) life. But since no one yet knows exactly how many years the new therapy will give patients, the Institute estimated its cost at 1.2-2.1 million dollars. Thus, “Novartis” in some way met expectations – albeit at the upper limit of the spread.

More expensive but cheaper

But patients themselves do not measure their lives with abstract thousands of dollars. They decide a specific question: they estimate what workarounds they have and how much they will cost. There is an alternative to Novartis on the market – this is Spinraza (aka Nusinernen) by Biogen, the world’s first drug for the treatment of spinal muscular atrophy. It works according to a different principle: it does not introduce a new gene into cells but adjusts the process of protein production from the SMN2 gene so that the SMN1 protein is obtained. But since the active substance here is not a DNA fragment, but an oligonucleotide, it disintegrates over time, and the injection has to be repeated.

Treatment with Spinraza costs 375 thousand dollars annually (and twice as much in the first year of therapy). Thus, the cost of one injection of Zolgensma pays for about five years of using Spinraza. However, “Novartis” sells exactly one injection for life, that is, in fact, “repair” the body, and “Biogen” – constant supportive therapy until the end of the patient’s days. Here, of course, it is worth making a reservation: we do not know for sure how true these promises are. Both drugs began to be used very recently, and not enough time has passed to judge how stable their effect is. But if we assume that both will work according to the instructions, then the Novartis medicine turns out to be a much more profitable investment.

Paradoxically, the world’s most expensive drug has made spinal muscular atrophy treatment cheaper. And this is a good example of how competition works. If there was no other way to help patients, Novartis could have announced an even higher price – since there would be nothing to compare with, and patients in the literal sense of the word would buy a medicine for death from the pharmaceutical company.

The competition was not fatal for any of the racers. Despite the impressive price tag, there are patients and insurance companies who are willing to pay for the “repair” of the MCA. At the same time, there are enough of those who choose Spinraza therapy: it is suitable for a larger number of patients (Novartis is prescribed only to children under two years of age, while neuronal damage is still somewhat reversible, and Spinraza is approved for any age).

In addition, Spinraza is now registered in dozens of countries around the world. Spinraza received registration in August 2019, however, as practice shows, there is not enough money for it either. There is still no final decision on its inclusion in the List of vital and essential dosage forms. It is not clear whether Zolgensma will be able to hope for registration and inclusion in the List.

Crush with quantity

Now the wheel of competition has turned once again: the third drug has finally entered the market – Evrysdi by Roche. It works in much the same way as nusinernen – it “corrects” the RNA that is produced from the SMN2 gene so that the output is the SMN1 protein. However, unlike its predecessor, the new drug is not an oligonucleotide chain, but three interconnected nucleotide analogs. The substance turns out to be much smaller in size and more stable, which allows you to change the delivery method: not to enter it into the spinal canal but drink the syrup, which the patient can do easily, without any involvement of doctors.

Time will tell which of the drugs will be more effective. At first glance, the results seem to be comparable: for example, about half of the children who were given Eurysdi or injected with Zolgensma learned to sit without assistance. The long-term prognosis in patients taking these drugs seems to be more favorable – about 90 percent survive within a year after starting treatment, while for those taking Spinraza this figure is about 60 percent. However, the effect of therapy strongly depends on how severe the disease is in a particular person and at what age they began to treat him.

The price of “Evrisdi” depends on the age of the buyer because the dosage is calculated by its weight. However, the maximum price is $ 340,000 (dosage for the average weight of a six-year-old child). And the lower threshold is much more democratic than that of other competitors – only 100 thousand dollars a year.

The list of drugs for spinal muscular atrophy will hardly end at three positions. The success of the top three spurs other players on the market to create their counterparts. With each new drug on the market, the price should fall. And after the patent expires, generics appear, each of which further drops prices. It is known, for example, that an average of five generics are needed to reduce the original price of a drug by 95 percent. From this point of view, you don’t need any new technologies to make the old ones cheaper, you just have to work hard on old patterns. The problem of super-expensive drugs can simply be solved by their quantity.

Category: General

Tags: children health, finance, medication, medicine, money, Spinal Muscular Atrophy


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