The reason for the shortage of semaglutide oral tablets

Why is it easier for semaglutide oral tablets to be in short supply?

In the past five years, the global average price (dark blue line) of Simeglutide API has decreased by 72%, from $3000K/kg to $843K/kg. The most competitive price in the market hit a historic low of $134K per kilogram in 2023. This strong downward trend can be explained by an increase in the number of market participants, which exacerbates competition on an economic level, and an increase in production often leads to economies of scale.

However, API price is only one element of drug manufacturing cost. Currently, there are three FDA approved semaglutide drugs on the market - Ozempic, Rybelsus, and Wegovy. However, semaglutide oral tablets are more prone to shortages, why is this?

The amount of raw materials (API) required for oral administration of Rybelsus is much larger than that for injections

Given that despite the decline in price curve, API costs remain relatively high, tablet manufacturers of Rybelsus generic drugs will face higher API fees. In addition, considering the current shortage of API raw materials, the supply of tablet versions may be limited.

Due to the extremely low bioavailability of the oral dosage form of semaglutide (Rybelsus less than 1%), a very high dose is required, which means that providing Rybelsus to one person requires the same amount of API as providing to over 100 patients receiving Ozempic treatment. However, Rybelsus' commercial success proves that people prefer oral treatment, which is not surprising: the pill form makes the drug more attractive to patients who do not like needles (because needles are inconvenient and uncomfortable).

What are the advantages of oral semaglutide besides avoiding injections

No need for cold chain storage: Oral semaglutide does not require refrigeration and can be stored at room temperature, reducing the complexity of storage and transportation. In contrast, semaglutide injection requires full cold chain management to maintain its stability and efficacy.

Significant weight loss effect: In March 2023, Novo Nordisk released relevant data from the Phase 3 study of oral semaglutide PIONEER PLUS. The research results at that time showed that among the people who took Smeglutide tablet once a day for 68 weeks and did not need to receive other type 2 diabetes drugs, the 50 mg and 25 mg doses could reduce the weight of subjects with an average weight of 96.4 kg by 9.2 kg (9.54%) and 7.0 kg (7.26%) respectively.

In the latest OASIS 1 study, patients in the oral group of 50mg semaglutide experienced an average weight loss of 17.4% (18.34kg), which further improved their weight loss effect compared to before.