‘There’s no money. You shouldn’t come here.’ Russian doctors and families are fighting to access the medicine sick children need to survive

A little girl from Russia’s Penza Oblast received a rare diagnosis: a genetic disorder that causes increasingly severe epilepsy, limiting the girl’s life expectancy to her teenage years. An effective treatment for her condition exists, but only outside Russia: within the country, the medication she needs is not officially registered. The girl’s parents used established laws to request government funding for the drug and even took government officials to court in the process, all to no avail. They are not alone: many Russians need lifesaving medications that have not been registered in Russia and cannot be sold in pharmacies there as a result. Accessing unregistered drugs requires incredible and sometimes even illegal efforts. Meduza correspondent Darya Sarkisyan reports on the lives of Russians who need unregistered drugs and explains what Russian residents do if they need immediate access to medications that cost several hundred thousand dollars a year.

Nastya’s story

While two-year-old Nastya Karlash was taking a walk in her hometown of Kamenka, a district capital in Penza Oblast, she had a spasmodic attack. Her mother, Maria, said her health had been typical for a child her age until then. The family took Nastya to a regional children’s hospital, but Maria said the doctors there were unable to diagnose her daughter. They also did not refer her to a federal hospital.

“The doctor said, ‘You have something that might be epilepsy. In Saratov, there’s a private clinic called EpiCenter—try going there, the specialists there aren’t bad,” Maria recalled. “In Saratov, they gave us a diagnosis of focal epilepsy. But they still weren’t entirely confident in the diagnosis. The seizures were happening more and more often, and they told us, ‘If you want, you can go to Moscow. There’s a medical center called Genomed where you can get analyzed on your own dime.’” And that’s what the Karlash family did. After three months of research, doctors gave Nastya a diagnosis of CLN2 disease, one of a group of disorders called neuronal ceroid lipofuscinoses or Batten’s disease. CLN2 is a genetic disorder that bolsters the development of epilepsy and makes muscle control difficult: a child who has it loses the ability to see, talk, and move without a wheelchair, typically passing away in her teenage years.

Doctors told Karlash that there was no cure for the disease but that a drug for it was soon to be approved abroad. In 2017, the U.S. Food and Drug Administration did indeed approve cerliponase alfa, which prevents the accumulation of substances in the body that allow the disease to develop and generate new symptoms. The drug, which is being sold under the commercial title Brineura, must be taken throughout the patient’s life. Clinical trials indicated that those who begin treatment early enough can live longer lives that may not differ substantially from the lives of those who do not have CLN2.

In order for any drug to be bought and sold freely in Russia, it has to be registered with the Russian Health Ministry. While nonregistered drugs must be purchased abroad for a specific individual, registered ones can be obtained in Russian pharmacies. In order to register a new drug, a pharmaceutical company must submit a request along with a sizeable set of documents, including reports on clinical trials conducted within Russia.

The law makes an exception for medicines that target very rare illnesses—conditions that affect fewer than 10 people out of every 100,000. Registration requests for these drugs can rely on clinical trials conducted abroad, which can lead to a shorter wait time for approval.

Unregistered treatments can be used on Russian territory in accordance with another set of rules. The easiest way for someone who needs a new drug to avoid bureaucratic difficulties is for that person to travel abroad and purchase the necessary medicine for themselves — and only for themselves — before returning to Russia along with receipts and other documents that can demonstrate their right to use the medicine if necessary. In 2019, some unregistered drugs will become available in the International Medical Cluster, a new project located in the Skolkovo Innovation Center on the southwest edge of Moscow. Hadassah Medical Skolkovo, which is run by an Israeli clinic, is the only medical center to have opened in the cluster thus far. The International Medical Cluster is legally exempt from the usual bureaucratic demands, and its staff say an individual patient could order and obtain the nonregistered medicine they need there in the course of a day. So far, the cluster can only use that loophole to provide treatment for cancer, but as new clinics open there, the range of medicines available should also expand. However, on January 31, reports emerged that even the cluster’s limited services are temporarily unavailable due to internal contradictions in the laws that govern them.

In certain cases, the state itself can purchase an unregistered drug. This route is available for patients who need hard-to-access treatments either because they do not respond well to medicine available in Russia or because the patient’s life is in danger. In other words, if a patient is legally entitled to treatment at no cost to them and they need a drug that happens to be nonregistered, that drug should nonetheless be provided for free. This bureaucratic procedure requires the approval of two medical commissions: first, a federal comission or a medical institution within the Russian Academy of Medical Sciences, and second, a committee within a regional medical institution where the patient has received treatment. These commissions are charged with determining whether the medication in question is truly necessary.

Online records of government purchases and comments from parents indicate that one institution capable of facilitating these acquisitions is the Center for Orphan Diseases and other Rare Children’s Diseases, which is housed in the Moscow City Children’s Clinical Hospital. Its director, Natalya Pechatnikova, wrote to Meduza that Moscow’s municipal health department provides funds for the hospital to buy these nonregistered medicines from a distributor after preparing a packet of documents for each patient who needs them. “We prepare and submit the documents,” Pechatnikova wrote. “Unfortunately, that process is neither fast nor simple. And, of course, the purchase and delivery process takes a substantial period of time.”

When the CLN2 drug Brineura was approved in the United States, Maria Karlash turned to the nonprofit “Dom Redkikh” (“House of Rarities”), which provides expert assistance on questions related to rare diseases. With help from the organization’s specialists, she obtained permission for Nastya to be hospitalized at the Russian Children’s Clinical Hospital. There, a committee of doctors concluded that it was necessary to administer Brineura even though the drug had not yet been registered in Russia. Maria obtained all the documents necessary for the purchase and contacted the Penza region’s health ministry herself to request the medicine her daughter needed.

“You should get a little thinner first”

The Karlash family received approval from the required federal committee with unusual ease. Natalya Savva is the organizational director of the “Dom s Mayakom” (“House with a Lighthouse”) Foundation, which supports a well-known children’s hospice by the same name. Savva argued that the current approval system doesn’t function as it should and that unnecessary obstacles can derail important requests even in their initial stages. “Among the children our foundation supports, a couple of kids legally receive unregistered medicine,” she said. “Usually, parents can’t get through the entire procedure. It is so complicated and doctors are so afraid to prescribe unregistered drugs that most children have to go without them, and the parents either have to transport the medicine from abroad themselves or buy it on the black market.” Savva explained that it is impossible to receive approval from a federal commission in the first place if the patient has not been hospitalized in a federal medical institution, which are few and far between in Russia and are located primarily in Moscow. If a patient is too sick to be moved or lives very far away from these institutions, that alone can be a serious obstacle. “It would be a good thing to permit long-distance consultations to solve this particular problem,” Savva said. “Telemedicine technologies have already been tried and tested. That would be an excellent policy: the [regional] doctor would be able to consult with the federal center directly and decide jointly whether the medicine at hand is demonstrably necessary or not. That way, the child wouldn’t have to make the trip.”

In late 2016, the spinal muscular atrophy (SMA) drug nusinersen, sold as Spinraza, was approved in the United States. In the U.S., it costs $750,000 for its first year and half as much in subsequent years. Olga Germanenko, who directs the “Semyi SMA” (“SMA Families”) foundation, does not know of a single person who received access to the drug, although she knows of 15 – 20 cases in which patients requested it from the government. Germanenko said the buck usually stops with the federal commission. She explained, “We have patients who are told, ‘Oh no, your condition is too severe, you need palliative treatment [to reduce pain until death]. You don’t need this drug.’ And they tell our patients who are a little stronger, ‘Oh no, you can’t demonstrate a vital need, you should get a little thinner first.’ I’m exaggerating here, of course, but that’s essentially the situation.”

Anastasia Tatarnikova, who leads the board of directors for Dom Redkikh, told Meduza about several similar cases. She added that problems can arise at the level of the regional medical commission as well. Regional approval is also mandatory, and patients do not always receive it even if federal medical employees find a pressing need for a nonregistered treatment. “The doctor thinks: in any case, I’ll be the one to blame,” Tatarnikova explained. “If I approve this, administrators will swoop in on me or even fire me. If I don’t approve this, the parents will come up to me after the fact and say that I stopped the whole process, and that’s called causing harm to the health of another, which can also make it hard to sleep at night. I feel very sorry for the doctors in these situations.”

Meduza interviewed several experts who also said doctors face administrative pressure to steer clear of nonregistered medications. One doctor at a large children’s clinic who asked to remain anonymous recalled one case in his institution when a young boy who had a rare disease needed an expensive, nonregistered drug. His parents went through the required process to obtain the medicine using state funds and received approval from the two required medical commissions, but they ultimately received the drug only after surmounting numerous bureaucratic obstacles. After that case, administrators at the federal clinic involved told its doctors “to put together fewer commissions.” In other words, they asked doctors who treat patients with rare conditions to stop requests for vital unregistered treatments before those requests even got off the ground.

“Now, some people don’t write anything in their recommendations, but they’ll jot something down on a scrap of paper and whisper, ‘You need this medicine,’” the children’s doctor said. “Some people write something like ‘Patients are warned that this medication is nonregistered’ in their recommendations and then include directions about how to take it on the hope that the patient will get ahold of the medicine on their own somehow and then follow their suggestions.”

Natalya Savva of the Dom s Mayakom Foundation said there seems to be an unspoken agreement among doctors to minimize costs and use what they have.

How to get $760,000 a year

In December of 2017, Maria Karlash submitted an application for her daughter’s medicine with all the necessary documents to the Health Ministry of Penza Oblast. Her application was received, and officials promised to issue a response in 30 days. After one month, the family received word that the ministry had lost their documents but later found them and would issue a decision in two weeks. The decision was a refusal. “When I got there, they said, ‘We can buy you this medicine if you give us the money,’” Karlash told Meduza. “If I had that much money at my disposal, I would never have gone there.” Karlash would need approximately 50 million rubles, or $760,000, every year—the full amount of the treatment’s cost in the United States. Maria said the regional health ministry’s unofficial justification for refusing approval was that it did not have enough funds to pay for Nastya’s treatment.

Russia’s Health Minister, Veronika Skvortsova, gave an interview to Komsomolskaya Pravda in which she claimed that the process for receiving unregistered drugs in Russia is “simple and absolutely free.” In fact, she was referring to the process of receiving permission to purchase a nonregistered drug, not to the purchase itself. “It seems like a simple mechanism on paper: you get a federal recommendation, write to the health ministry, and they give you permission to import the medicine five days later,” Olga Germanenko from Semyi SMA said. “Everything would be great if only this mechanism had the finances to back it up. In reality, they give you permission, but it hasn’t occurred to anyone to think about where you’re going to get the money to buy this drug and have it shipped to you.”

Charitable foundations tend to take on a significant portion of the fundraising that becomes necessary in these cases, but when a family needs a sum as large as the cost of Nastya’s medicine, not a single foundation is able to take on the task. “We see families all the time who try to raise an insane amount of money on the Internet, and individual philanthropists occasionally pitch in,” Olga Germanenko said. “So far, no one has raised enough money to pay for even a single year’s treatment. And when that year ends, what do you do? This is a drug you have to take for your whole life.” Anastasia Tatarnikova from Dom Redkikh said she reached out to various foundations in one case when the regional health ministry involved was unable to pay for a patient’s treatment. All of her requests were rejected. One of Russia’s larges charitable funds, “Podari Zhizn” (“Give Life”), spent almost 150 million rubles, or nearly $2.3 million, in 2018 on a special program specifically intended to pay for nonregistered medicine. That amount of money is enough to treat only three patients like Nastya Karlash. Even so, Podari Zhizn paid for 60 percent of all the nonregistered drugs that were imported into Russia during the course of its program.

Dom Redkikh pointed Meduza to a 1994 government order that assigned regional governments responsibility for covering treatment for children with disabilities. In 2013, a letter from Russia’s federal Health Ministry to its regional counterparts affirmed that order. Nonetheless, regional officials often complain that the sums in question are too great. Health care experts along with patients and their parents say that one common argument among regional bureaucrats is that spending money on very costly treatments for a few people might prevent the government from funding insulin purchases for thousands of people with diabetes. Anastasia Tatarnikova of the Dom Redkikh board of directors acknowledged that similar arguments will always be available, but that doesn’t make them airtight. She argued that regional health ministries can request additional funding from the federal budget by creating a special program to record, justify, and account for additional expenses. Such programs are already active in certain regions. When asked why that solution is not always available when it is most needed, Tatarnikova answered that bureaucratic inertia is still an obstacle. She added that some officials may not see a single child’s quality and length of life as a particularly important issue.

Russian law outlines 12 severe conditions for which the federal government must provide treatment using its own budget. Predictive estimates put the cost for those medicines in 2019 at 10 billion rubles, or slightly over $150 million. That is a sizeable financial load for any country, and different governments attempt to lessen it in different ways. One common tactic is to strike a deal with pharmaceutical companies such that the government must pay for a given drug only if it actually improves the patient’s condition.

“Ultimately, it’s always a result of negotiations between government representatives and pharmaceutical companies,” said Raja Shankar, who co-chairs the Medicines in Health Systems working group for the international organization Health Systems Global. “New medicines can be very expensive and economically unprofitable for governments. So they start negotiating, and in most cases, especially if both sides promise not to disclose the final price, the negotiations end well. In some cases, the conditions they agree on only apply to a certain group of patients such as those who benefit more from the medicine or those who need it most.”

For example, in 2017, negotiations between the British National Health Service and the company that produces the breast cancer treatment Kadcyla (ado-trastuzumab emtansine) enabled the British government to provide the treatment to patients free of cost. The drug had previously cost approximately $115,000 to prolong the life of a single patient with terminal cancer by an average of six months. The amount by which that cost decreased was not disclosed, but the company’s discount was sufficient for the government to cover the cost of the drug.

Not on the government’s dime

Maria Karlash said the message she received from officials in the Penza regional health ministry was “There’s no money. You shouldn’t come here. Nothing will change.” Nastya’s father, Mikhail, responded by suing the ministry. The family had already made contact with Kirill Kulyaev, an attorney from Dom Redkikh who helped them compile all the necessary documents for their request. The Karlash family won its first court case, but the health ministry appealed that decision. By the end of August 2018, it had received permission not to fund Nastya’s treatment even though Russia’s federal regulatory agency for health issues took her side in the case. The court’s final decision, which Meduza has on file, indicates that Nastya has the right to receive the medicine she needs on Russian territory but that the government has no obligation to pay for her treatment.

Natalya Smirnova, another attorney from Dom Redkikh, said patients face obstacles in acquiring nonregistered drugs primarily when the cost of the medicine is very high. In most other situations, patients rarely need to go to court, and it can even be enough to submit a complaint to prosecutors. “But there are regions where, even after a successful court case, they don’t cover the cost of the medicine, and families have to request an order that mandates enforcement of the court’s decision,” Smirnova said. “In my practice, I’ve seen cases where we waited for eight or nine months for an order to be enforced. We’ve had patients who were dying while their cases were considered. Some of them died when the court made its decision; others died when they received an order for enforcement.”

Healthcare specialists believe the Karlash family would face far fewer difficulties if CLN2 were included in one of two regulatory lists. The first is called “the 12 nosologies” in professional circles. Until 2019, there were only seven “nosologies.” Patients who have illnesses included in the list can receive very expensive medicine through the government’s budget; these are the 10 billion rubles projected for federal spending in 2019. Olga Germanenko said having a loved one’s illness included in the list is a dream for many families because it guarantees far more reliable access to lifesaving medicine.

The second list is the federally backed “Catalogue-24,” which has since the beginning of 2019 encompassed 19 conditions whose treatment must be funded through regional budgets. Experts were unable to tell Meduza why CLN2 is not included in that list. Anastasia Tatarnikova said she has tried for many years to determine what criteria allow an illness to be included in Catalogue-24. She explained that the criteria were never clear. However, she said some experts believe the list is intended to cover life-threatening illnesses for which internationally registered treatments already existed when the list was created, which was in 2012. Tatarnikova’s research indicates that at least 13 more illnesses have since come to meet those criteria, including CLN2.

The “7 nosologies” list was expanded in the summer of 2018. At that time, State Duma deputies proposed several conditions that would add to the case for including a new illness in that list: “the expense of the medicine, the dominance of children’s cases in the category [of illness] at hand, and the possibility for patients with the rare illness to become maximally socialized.”

None of those criteria are part of the legal record, and even they are not precisely defined. “It must be noted that the five conditions [that were added] are all over the place when it comes to those criteria,” Tatarnikova said. “And if there are criteria, [policy] decisions should correspond to all of them.”

Options

Now, the Karlash family has almost no options left. In December 2018, they lost their appeal. Judging by the experiences of other patients, every other hope they have for seeking treatment is, to say the least, unrealistic.

One option is to travel abroad for treatment and request government funding for that process. Legally, that is possible if a patient cannot find lifesaving treatment within Russia. Olga Germanenko of the Semyi SMA foundation said she has heard of several families who pursued that route unsuccessfully. In one case, two federal institutions approved a family’s petition and recommended that a child be sent abroad. “The Health Ministry’s commission refused,” Germanenko said. “In their official letter, they wrote to the [child’s] mother that, essentially, we won’t pay for this treatment, but don’t worry: we’re planning a clinical study, try signing up for that. But the study was for an experimental drug whose effectiveness had not been proven, and the study was placebo-controlled. Who could guarantee that the child wouldn’t end up in the control group?”

Clinical trials could really become a decent alternative to treatment outside Russia, but only for drugs in their final round of trials that are likely to become registered soon afterward. Healthcare experts told Meduza about families that used their own funds or relied on donors to find experimental treatments abroad and ultimately paid only for the medical services that accompanied the medicine. “But if the drug is already registered with the FDA and EMA [European Medicines Agency], you can’t send your patients anywhere,” explained Artyom Sharkov, the doctor leading Nastya Karlash’s treatment. “In cases like that, I tell my patients that I will let them know if any new criteria for inclusion in clinical trials arise. For example, they will sometimes take younger brothers and sisters of children who are already seriously ill if their siblings have the same genetic variant and it’s already understood that they may begin experiencing symptoms soon.”

Some pharmaceutical companies also organize early access programs, which can provide a new drug for free over the first several months of treatment. However, these programs typically arise only if the government can guarantee that a drug will be registered or that the government will soon begin funding purchases of the nonregistered drug. Anastasia Tatarnikova said she has gotten word that the Russian company Biomarin plans to register the CLN2 drug Brineura, but that request for registration will take at least a year to go through. Biomarin’s central office did not respond to Meduza’s request for comment.

A small market with low profit margins

Sources in the healthcare industry confirmed that it tends to be less difficult to receive funding and approval for medicine that is already registered in Russia; there are fewer reasons the government might lean on to refuse those requests. That said, Federal Health Minister Veronika Skvortsova has said her ministry cannot force pharmaceutical companies to register drugs. While she is technically correct, the agency can influence the registration process. Natalya Savva of Dom s Mayakom explained that, in some cases, companies have no incentive at all to register a new treatment: registration requires new clinical trials on Russian territory, but those efforts are almost never profitable because the market for drugs that target rare diseases is so small.

A number of treatments have made news after those who needed them fell victim to those limits. One was a plaster infused with fentanyl, which was sold in Russia for adult use only until 2017. In the summer of 2018, a Moscow resident named Yekaterina Konnova purchased another such treatment for her son Arseny, who was seriously ill. The diazepam microclyster she found on the Internet failed to improve Arseny’s condition, and Konnova attempted to sell it. She was charged with the sale of a psychotropic substance, but prosecutors withdrew that case in response to widespread social outcry.

The fentanyl plaster ended up being one of a very small number of treatments that became more widely available after government negotiations. “In all likelihood, this was a very singular exception to the rule,” Savva said. “At that point, there was a huge government campaign on anesthesia, and we were also able to come to an agreement with the company involved. This was all possible because of communication. The government has to compromise. The conditions for registration are often disadvantageous for pharmaceutical companies, and then we’re the ones who have to grab them by the shoulders and shake them so that they provide treatment for our kids. It’s just silly.” Savva argued that the government should take a leading role in the issue and develop policies that prioritize lifesaving drugs.

Representatives of Russia’s Association of International Pharmaceutical Manufacturers declined to respond to questions about the factors that can affect international companies’ decisions on whether to register expensive medications in Russia.

Natalya Savva said patient organizations can also play a role in negotiations. In December 2018, a request to register the spinal muscular atrophy drug Spinraza was submitted to Russia’s Health Ministry. The medication had been approved in the United States two years previously. Nonetheless, Olga Germanenko said the company that produces Spinraza was hesitant to enter the registration process. The Semyi SMA foundation reached out to the company’s representatives and discussed the issue with them extensively. Germanenko believes the presence in Russia of such an active patient organization ultimately played a significant role in the pharmaceutical firm’s decision to pursue registration. “The company can see how many patients there are, and they can see that those patients care and will fight to receive treatment,” Germanenko said.

Nastya Karlash’s doctor, Artyom Sharkov, argued that doctors like him also have a role to play in stimulating the registration of new drugs. He explained, “I make regular efforts to spread information about early diagnostics. Essentially, as long as there isn’t a defined pool of patients that has formed some kind of organization, nothing will happen. But in order for that kind of group to form, someone has to diagnose [patients] early and collect their names in a registry.” That process, Sharkov asserted, must be driven by health care providers.

Now, Nastya Karlash is four years old. She will turn five in April. As a child with a disability, she receives antiepileptic medication from the government, but it does not always prevent her seizures. “Right now, things are bad for us,” Maria said. “She has stopped walking, she doesn’t talk anymore—just syllables—and she can’t eat by herself. She’s always trying to get up on all fours, but she usually falls down: she doesn’t have the strength in her arms or legs. She can have seizures at any time, and she can’t warn us about them, so we can’t see them coming at all.”

Once CLN2 symptoms appear, patients have only a few years to get back what they have lost. Artyom Sharkov said there will come a time when even Brineura will be of no use to Nastya, and the only option left will be palliative care to reduce her symptoms until she dies.

Following the scandal that surrounded Yekaterina Konnova’s case, Russia’s Health Ministry invited several healthcare experts in the nonprofit sphere to a meeting. Natalya Savva and Lida Moniava of Dom s Mayakom were among them. After the meeting, Moniava wrote on Facebook that the ministry had promised to issue an explanation by October 15, 2018, regarding what families can do when the registration system does not work for them. No such explanation had been released by the time of this writing. For two months, the Health Ministry failed to respond to Meduza’s inquiries regarding access to nonregistered medications.