Montelukast sales 22%↓ in 2 years and adds impurity issue

From ₩120 billion in 2019 to ₩95 billion last year…sales of original 'Singulair' drops 32%

Side effect issue + prolonged COVID-19 crisis… ‘NDPA impurity’ emerge as variable to add on issue

The market for the montelukast ingredient used to treat allergic rhinitis and asthma has contracted for two consecutive years.

 

The reduction is analyzed to be due to the combined effect of the US FDA’s side effect warning request for the ingredient in 2020 and the prolonged COVID-19 crisis.

 

Industry eyes are on how the impurity issue that recently emerged would additionally affect the market.

 

◆Conflicting results by product… Singulair ↓ 32% vs Monterizine ↑ 15% According to the industry research institution UBIST on the 25th, outpatient prescription sales of the allergic rhinitis and asthma treatment market for montelukast was ₩94.8 billion last year.

 

The market had risen from ₩76.1 billion in 2016 to 121 billion in 2019 but had seen a decline for two consecutive years since.

 

Compared to 2019 when the market expanded to its greatest, the market had shrunk 22% over the recent 2 years.

 

Montelukast is one of the most common drugs used to treat allergic rhinitis and asthma.

 

The original drug is Organon Korea’s Singulair.

 

In Korea, MSD Korea received approval for the original drug in 2000, and around a hundred domestic pharmaceutical companies are selling generic versions with the same ingredient.

 

Most of the key products were unable to avoid the reduction in their prescription amount.

 

Sales of the market lead Singulair shrunk 32% from ₩39.2 billion in 2019 to ₩26.5 billion last year.

 

Other montelukast drugs also saw a double-digit reduction in sales.

 

HK Inno.N’s ‘Lukio’ dropped 31% (₩12.8 billion→₩8.8 billion), Hanmi Pharmaceutical’s ‘Montezal’ dropped 35% (₩7.3 billion→₩4.7 billion), Hutec Korea Pharmaceutical’s ‘Singuldown’ dropped 26% (₩5.3 billion→₩3.9 billion), Daewon Pharmaceutical’s ‘Singuluka’ dropped 42%(₩3.1 billion→1.5 billion).

 

On the other hand, prescription of some products has increased greatly.

 

Sales of Hanmi Pharmaceutical’s ‘Monterizine’ increased 15% from ₩8 billion to ₩9.3 billion in the same period.

 

Monterizine is a combination of montelukast and a third-generation antihistaminic agent ‘levocetirizine.’ It is the only combination drug sold in Korea.

 

◆ FDA’s ‘black box warning’ and ‘prolonged COVID-19 crisis’ cause combined effect Analysts believe that this was a combined effect from the prolonged COVID-19 and FDA’s side effect warning.

 

The FDA required a ‘Black box warning’ on montelukast products in March 2020.

 

The black box warning is the FDA's most stringent warning for drugs and medical devices in the market.

 

In particular, the FDA strongly advised health care providers to avoid prescribing montelukast to patients with mild allergic rhinitis, as it is the FDA’s judgment that the risk outweighs the benefits for mild patients.

 

According to the FDA, serious adverse reactions, including suicide, have been reported with the use of Singulair since 2008.

 

Some of these side effects occurred while the patients were treated with montelukast and disappeared after discontinuing the drug.

 

The prolonged COVID-19 incidence had also reduced the prescriptions.

 

The pediatric clinics have been one of the areas most affected by the COVID-19 crisis.

 

Since most patients with allergic rhinitis and asthma are children and adolescents, the prolonged COVID-19 crisis has aggravated the reduction in prescriptions of montelukast.

 

◆MFDS orders NDPA impurity tests…rises as a ‘new variable’ in market The industry has also been paying attention to the impurity issue that had arisen recently.

 

The Ministry of Food and Drug Safety had recently ordered pharmaceutical companies to conduct an investigation into their montelukast ingredient and finished products for impurities and submit the reports by April 25th.

 

This precautionary measure was issued after the ministry received safety information that N- nitrosodipropylamine (NDPA) was detected in the API montelukast.

 

The NDPA is a new nitrosamine impurity that has been identified.

 

Since 2018, two types of nitrosamine impurities, - ‘N-nitrosodimethylamine (NDMA)’ and ‘N-nitrosodiethylamine (NDEA)’ were detected in valsartan, ranitidine, and nizatidine.

 

The MFDS predicts that NDPA occurred in the API manufacturing process of montelukast.

 

Contrasting opinions have been produced on how the impurity concern may affect prescriptions in the field.

 

Those who believe that impurity will not affect the market are focusing on the fact that such impurity issues have risen every year.

 

After the valsartan incident in 2018, impurities were consecutively detected in ranitidine, nizatidine, metformin, losartan, varenicline, etc., building resistance among frontline clinics and hospitals regarding the issue.

 

The government had also initially suspended the sale of all items, but recently ordered only specific lot numbers to be recalled.

 

Others who have opposing views argue that it is too soon to predict that the impurity concern will not be significant, given that the montelukast are mainly prescribed to children and adolescents, unlike other items.