One more step
The world's second drug based on RNA interference has been approved
Polina Loseva, N+1
The US approved a second drug based on RNA interference (FDA approves first treatment for inherited rare disease).
The new drug is intended for people with acute hepatic porphyria, a genetic disease during which hemoglobin precursors accumulate in the tissues. There are not so many patients who could benefit from the drug in the United States, so its starting cost is almost half a million dollars. But if it proves effective for a wider range of patients, the manufacturer promised to lower the price.
A year ago, the first drug based on RNA interference appeared in the world. Then analysts said that this technology caught on surprisingly quickly: only 20 years have passed since the discovery of the mechanism itself in invertebrates, 12 since the Nobel Prize was awarded for this discovery. And so the development continues: the same company that debuted last year, Alnylam Pharmaceuticals, has received approval for its new drug.
The principle of RNA interference is as follows: before building any protein, the cell copies information about it from DNA to matrix RNA. This RNA then exits the nucleus into the cytoplasm of the cell, where it is used to create a protein. At this stage, the process can still be stopped: for this, the cell produces small interfering RNAs. They selectively adhere to the matrix RNA of an unnecessary protein and thus form a double-stranded RNA molecule. But since all RNA in a cell, As a rule, consists of one chain, such a molecule arouses suspicion, and it is broken down by a special protein complex. As a result, the matrix RNA decays, and protein synthesis stops.
The new drug, givosiran, is directed against another protein, δ–aminolevulinic acid synthase (ALAS1). This enzyme is involved in the production of heme (the most important part of hemoglobin). If it is too active, and the enzymes following it in the synthesis chain are not active enough (as happens with hepatic porphyria), then an intermediate product of heme synthesis, porphyrin, begins to accumulate in the tissues. It is especially toxic to nerve cells, so the deposition of porphyrin can cause pain, convulsions and paralysis.
Givosiran is a small interfering RNA that suppresses the production of ALAS1. The carbohydrate marker GalNAc is "sewn" to it, for which it is selectively captured by liver cells. Thus, givosiran acts pointwise on the liver, where heme is produced, but does not enter the cells of other organs. In clinical trials, half of the patients with acute porphyria managed to completely remove the attacks of porphyria, on average, the drug reduced the number of seizures by 70 percent.
However, the total number of people who could benefit from this medicine is not so great. It makes sense to use it for severe forms of porphyria with frequent attacks, this is 3-5 percent of all patients. According to the company's experts, there are about 3,000 of them in the USA and Europe. Therefore, the initial cost of givosiran, which is designed to recoup development costs, is quite high – 575 thousand dollars a year.
Nevertheless, the company's representatives do not exclude the possibility that they may have underestimated the number of potential patients. And we are ready to reduce the cost if it turns out that there are actually more people interested in the drug. This is an important precedent in the orphan drug industry, and it is hoped that similar agreements will be concluded by other manufacturers of drugs for rare diseases that risk not paying off.
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