- We should not lose sight of those who are most affected by fate, i.e. patients with rare diseases," said Anna Jasinska, spokesperson for the Medical Council of Rare Diseases, during the September meeting of the Expert Council on Rare Diseases. The experts highlighted, among other things, the need to extend diagnostics to include genetic testing. They also drew attention to the need to extend treatment to those groups of patients whose needs are not yet covered.
- We can be proud of our access to the particles used in treatment. I hope that the Rare Diseases Plan 2021-2023 is only the beginning of a great activity. It is the start of a very important process that must continue," emphasised Dr Janusz Meder, President of the Polish Union of Oncology
As Grażyna Mierzejewska of the Polish Union of Oncology, an expert in the Medical Rationale of State, pointed out, 32 molecules with therapeutic relevance for this type of condition had already been registered by September.
- Our aim is to provide diagnosis and treatment, but also comprehensive and all-round assistance. The biggest problem we have is covering patients with holistic care. This is the most important part of all healthcare. After covida, we have a huge health debt to patients in Poland, but a special one to patients with rare and ultra-rare diseases," noted Professor Zbigniew Żuber, chairman of the MRS Rare Disease Expert Council.
GENETIC TESTING NEEDED
According to experts, one of the most urgent needs now is to develop recommendations for the diagnostic management of genetically determined diseases. Rules need to be developed and certification of laboratories performing genetic testing needs to be implemented, but also due access to non-genetic testing needs to be ensured.
As emphasised by Professor Anna Latos-Bieleńska from the Department of Medical Genetics at the Poznan University of Medical Sciences, access to molecular and genetic diagnostics is crucial for establishing a diagnosis, which in turn is extremely important for patients and their families, even if no treatment can be offered.
- When the molecular defect is known, it turns out that the patient can often be helped even if there is no dedicated drug. In only about 5 per cent of cases is an effective therapy developed, and this is an opportunity for such a patient to have a completely different quality of life. Those with a diagnosis, on the other hand, can also participate, for example, in clinical trials," pointed out Prof. Anna Latos-Bieleńska.
Improved access to high-throughput testing methods is needed, she added. The annual demand for microarray testing is estimated at 8-10,000 tests, for MGS targeted panels at 5-6,000, and for exome sequencing: 4-5 thousand.There is also a need to include genetic testing in patients who have died in reimbursement. This could contribute to the diagnosis and treatment of the patient's relatives who may have the same molecular defect as the patient.
Prof. Jolanta Sykut-Cegielska, national consultant in Metabolic Paediatrics, drew attention to the need for a uniform register of rare diseases and the patients who suffer from them. Until it can be developed, it is difficult to talk even about the scale of the problem. Newborn screening and selective and symptomatic screening should be the pillars of a diagnostic system, she pointed out.
Prof Anna Kostera-Pruszczyk from the Department of Neurology at the Medical University of Warsaw noted that the implementation of the plan for rare diseases requires many complex arrangements. Particularly important, in her opinion, should be ensuring a smooth transition of the patient from a paediatric centre to an adult facility once they reach adulthood. Expert centres will also play a very important systemic role.
HAEMATOLOGY PATIENTS HAVE BETTER ACCESS TO MEDICINES, BUT NEEDS ARE STILL
Much of the discussion was devoted to haematological and haemato-oncological diseases. Again, fast and effective diagnosis is of paramount importance. Prof Ewa Lech-Marańda, national consultant in haematology, acknowledged that haematologists have access to genetic testing, but that this is reserved only for tests performed as part of hospital treatment.
- The entire diagnostic focus, meanwhile, is translated into outpatient specialised care, i.e. haematology clinics. The vast majority of patients have outpatient diagnostics. It is therefore important to finance tests and ensure access to the specialists who perform them," pointed out Professor Ewa Lech-Marańda.
The second element of a well-functioning system should be adequate access to medicines.
- Access to specialised medicines has improved greatly in recent years. We have gained access to 30 new medicines for haematological indications, but these needs will continue. We look forward to continuing to work with the Ministry of Health," she added.
However, the treatment of primary immune thrombocytopenia is problematic. Two therapies are available to patients under drug programmes: these are eltrombopag and romiplostim. Until recently, patients who failed to respond to other therapies could count on treatment with avatrombopag as part of rescue access to drug technologies. In July, this option was ruled out after the Agency for Health Technology Assessment and Tarification issued a negative opinion for this therapy. However, a reimbursement process is underway.
- Patients who have impaired liver function cannot receive the reimbursable, orally administered eltrombopag, which is hepatotoxic. In such cases, avatrombopag, which is up to four times more potent in stimulating platelet production, can be used. There are also people who do not respond to all lines of treatment, including splenectomy (excision of the spleen - editor's note), administration of eltrombopag and romiplostim, and have severe thrombocytopaenia. In these patients, avatrombopag can have a good effect," pointed out Professor Jadwiga Dwilewicz-Trojaczek from the Department of Haematology and Transplantology of Internal Diseases at the Medical University of Warsaw.
Professor Dwilewicz-Trojaczek also highlighted the needs of patients with an ultra-rare disease such as nocturnal paroxysmal haemoglobinuria. The prognosis of patients before the introduction of complement inhibitor therapy was poor. 30 per cent of patients died within five years of diagnosis. After approval, treatment with C5 inhibitors improved the prognosis, but still about 40 per cent of patients respond suboptimally or not at all. 15 per cent require red cell concentrate transfusion. The new drugs may prove to be an opportunity for these groups of patients.
- A C3 complement inhibitor was registered in 2021. It appears that it may be effective in people who have responded suboptimally to C5 treatment. The drug may be important because it significantly improves blood count, reduces intravascular haemolysis and inhibits extravascular haemolysis. Importantly, the drug is administered subcutaneously," added Professor Jadwiga Dwilewicz-Trojaczek.
Prof Wieslaw Jedrzejczak from the Department of Haematology, Oncology and Internal Medicine at the Medical University of Warsaw highlighted the importance of caplacizumab in the treatment of acquired thrombotic purpura.
- It is an antibody that may play a beneficial role in protecting the lives of patients in whom plasma exchange and plasma transfusions with proteins destroyed by the autoimmune mechanism characteristic of the disease have failed, said Prof Jędrzejczak.
Patients struggling with T-cell anaplastic lymphoma, meanwhile, are waiting for wider access to brentuximab vedotin, a monoclonal antibody currently used to treat refractory relapsed disease. Clinical trials, however, have confirmed its efficacy also in first-line treatment.
BREAKTHROUGH IN THE TREATMENT OF CYSTIC FIBROSIS
Since March, cystic fibrosis patients in Poland have gained access to reimbursed treatment with causative drugs. According to Professor Dorota Sands, head of the Cystic Fibrosis Unit at the Mother and Child Institute in Warsaw, the implementation of this drug programme is a huge challenge for the healthcare system, but also a reason for great joy. Patients are currently being enrolled in treatment.
- The inclusion rate is between 50 and 80 per cent of those eligible. It is a powerful drug that acts in multiple ways and requires monitoring. The drug is already being administered according to scheduled appointments, informed Prof Sands.
However, there are still unmet needs in the treatment of cystic fibrosis. This is primarily the extension of the programme to children from the age of six, which is in line with the characteristics of the drug. As Prof Dorota Sands points out, causal treatment can be a therapy that will cover around 80-85 per cent of patients. The remaining group are those in whom cystic fibrosis has a genetic basis that cannot be modulated by the drugs available to date. For them, hope may lie in the development of gene-editing technology. Projects using it are currently in pre-clinical trials.
REFERENCE CENTRES NEEDED, EARLY DIAGNOSIS AND POST CLINICAL CARE
Prof Jolanta Sykut-Cegielska, national consultant in Metabolic Paediatrics, drew attention to the need to introduce genomic testing into the newborn screening package. This would allow early detection of rare diseases such as Pompe disease, among others. Pompe disease can manifest itself already in newborns and then usually has a rapid course and a high risk of death. In the second phenotype, diagnosed in young adults, symptoms include fatigue and proximal myopathy. Although the disease has a milder course than in the first phenotype, it still leads to severe complications such as respiratory failure. Treatment, which involves giving the patient the enzyme acid maltase, has shown good results. Genetic treatment is also being developed. As Prof Jolanta Sykut-Cegielska emphasised, the main focus should be on establishing reference centres that would manage patients with Pompe disease and where the optimal time to start treatment would be selected individually.
Research into genetic treatment is also ongoing for Wilson's disease. According to Prof Zbigniew Żuber, chairman of the MRS Rare Disease Expert Council, a drug programme using trientine tetrachloride has been available for patients since last September. The drug is used in the event of side effects with basic treatment with d-penicillamine. This succeeds in covering a larger number of patients with therapeutic management.
In contrast, there is a problem for those with alpha-mamnosiasis in that the clinical trial programme with patients is coming to an end.
- It is an ultra-rare disease. There are maybe a dozen patients in Poland. Now we are faced with the problem of what to do next. As a doctor I would like to treat all patients, but we are not in a position to decide. As a rule, it is possible to continue treatment if the payer agrees and there is adequate funding. Perhaps the Medical Fund is the right place to apply for additional funds. I know that in many European countries there is the possibility of treatment under programmes similar to emergency access to drug therapies. In our country, however, prior registration and approval from decision-makers is needed," noted Prof. Żuber.
As the professor added, usually the contract for conducting clinical trials in Poland includes a clause whereby the manufacturer ensured that patients could receive therapy even after the trial ended.
ARE MEDICINES BEING REGISTERED TOO QUICKLY?
The problem of drugs being registered too quickly was highlighted by Wojciech Wysoczański, deputy director of the Health Care Services Department in the Analytical Branch Unit in Wrocław of the Agency for Health Technology Assessment and Tarification. In his opinion, the quality of clinical trials is drastically decreasing, which hinders the work of the agency.
- For many medicines, the registration process is too fast. The risks associated with their use are passed on to patients and doctors. What should be done at the clinical trial stage is not completed. Expenditure on drug interventions is increasing very rapidly, while solutions to patients' needs for non-drug interventions remain outside the mainstream, assessed Wojciech Wysoczański.
CONTROVERSY OVER AMENDMENTS TO THE REIMBURSEMENT ACT
Dr Michal Jachimowicz, an expert in HTA, addressed the planned changes to the Reimbursement Act. The most significant one is the one concerning the valuation of QALYs, i.e. an additional quality-adjusted life year.
- The new reimbursement law is to not allow reimbursement of therapies for which the QALY costs more than PLN 322,000. If this provision were in force today, for a year of therapy that improves quality of life by 10 QALYs, one could pay at most around 32 thousand, or PLN 2683 for a month's therapy. How many therapies do we know of that cost just over PLN 2,500 per month and are used for rare diseases? Do they really improve the quality of life? - the expert asked.
Attorney Piotr Mierzejewski of the Ombudsman's Office cited the findings of the Ombudsman's Commission of Health Experts. According to them, patients with rare diseases are discriminated against in access to diagnostics in Poland and are at risk of using low-quality genetic tests. According to the experts, newborn screening diagnostics should be extended and the pharmacological offer for patients with rare diseases should be increased. In their view, the state is particularly deficient in terms of child custody in access to services and reimbursement.
Source: medexpress.co.uk