(Health Korea News / Lee Chung-man) As endothelin A (ETA) receptor antagonists are gaining attention as treatments for cancer and kidney disease following pulmonary hypertension, attention is focused on whether generic products can also benefit.
Endothelin is a peptide secreted by vascular endothelial cells and has the function of constricting blood vessels. There are three subtypes: ET-1, ET-2, and ET-3, of which ET-1 is the most potent vasoconstrictor.
ET-1 prevents hypotension by binding to the ETA receptor, causing vascular smooth muscle contraction and an increase in blood pressure. However, if this effect is excessively expressed, it puts a strain on the heart and causes pulmonary hypertension.
ETA antagonists act by antagonizing the ETA receptor, preventing ET-1 from binding to the ETA receptor. This can be used to treat pulmonary hypertension.
This agent has established itself as a standard treatment for pulmonary hypertension, for which there was no clear treatment, but its potential for treating cancer and kidney disease is also being explored recently.
First, in the case of cancer, it was discovered that ET-1 plays an important role in the proliferation and metastasis of cancer cells. In addition to vasoconstriction, ET-1 induces the formation of new blood vessels, and new blood vessels provide nutrients such as blood and glucose to cancer cells. Due to this effect, it is currently being studied in ovarian cancer, prostate cancer, and colon cancer.
In the case of kidney disease, it is receiving attention as a treatment for chronic kidney disease (CKD). CKD is a disease in which kidney function gradually declines, and when ET-1 is overexpressed in the kidney, it constricts blood vessels in the kidney, lowering glomerular filtration function and ultimately damaging kidney function.
The pharmaceutical and biotechnology industry is hopeful that ETA antagonists will provide an alternative to address unmet medical needs in the areas of ovarian cancer, prostate cancer, colon cancer and CKD, where effective treatment options are still lacking.
According to our investigation, there are currently 107 ETA receptor antagonist candidates under development worldwide. Of these, 10 ETA antagonists are being developed as treatments for cancer and kidney diseases, not pulmonary hypertension.
In Korea, there is no movement to develop ETA receptor antagonists as new drugs yet. Instead, they are attempting to develop a generic version of ‘Opsumit’ (ingredient name: macitentan), the only ETA antagonist approved domestically by Janssen in the United States.
‘Opsumit’ was approved as a treatment for pulmonary arterial hypertension by the U.S. Food and Drug Administration (FDA) in October 2013. The Ministry of Food and Drug Safety in Korea approved ‘Opsumit’ for the same indication in November of the following year.
The drug was originally owned by Switzerland’s Actelion, and Janssen acquired ‘Opsumit’ when it acquired Actelion for $30 billion in January 2017.
‘Opsumit’ has joined the ranks of blockbuster drugs since joining Janssen. It has generated revenue of 3.8 billion dollars (about 5 trillion won) in 2023. The same is true in Korea. According to IQVIA, ‘Opsumit’ recorded sales of 17.4 billion won in 2022.
Domestic pharmaceutical companies are moving to conquer the ‘Opsumit’ generic market. ‘Opsumit’ had a material patent expiring in March 2023 and a composition patent expiring in October 2027.
In May 2022, Samjin Pharmaceutical filed a request for a negative scope confirmation trial for the composition patent and attempted to invalidate the patent. In April of the following year, it received a decision to establish the request, and based on this, it launched ‘Masiten Tablet’ (ingredient name: Masitentan) in May 2023.
Daewoong Pharmaceutical also obtained approval for ‘Masimit Tablet’ (ingredient name: Masitentan) from the Ministry of Food and Drug Safety in May of last year. As a side note, Daewoong Pharmaceutical failed to successfully avoid the patent for the ‘Opsumit’ composition, so ‘Masimit Tablet’ is currently not on the market.
The industry expects more companies to develop generics in the future, as research suggests that ETA receptor antagonists may also be useful in treating cancer and kidney disease.
An industry insider said in a phone call with Health Korea News on the 12th, “ETA receptor antagonists are still in the early stages of development, and even the original ‘Opsumit’ has not obtained the relevant indications,” adding, “However, considering the unmet medical needs in the fields of cancer and chronic kidney disease, it seems that top pharmaceutical companies will be the first to jump into research and development.”
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Source: www.hkn24.com
