Tezacaftor Production Cost Reports

The report provides a detailed analysis essential for establishing a tezacaftor production plant. It encompasses all critical aspects necessary for tezacaftor production, including the cost of tezacaftor production, tezacaftor plant cost, tezacaftor production costs, and the overall tezacaftor production plant cost. Additionally, the study covers specific expenditures associated with setting up and operating a tezacaftor production plant. These encompass production processes, raw material requirements, utility requirements, infrastructure needs, machinery and technology requirements, manpower requirements, packaging requirements, transportation requirements, and more.

Tezacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) corrector medication. It is used in combination therapies to treat cystic fibrosis (CF) in patients with specific CFTR gene mutations. It helps in proper folding and trafficking of the defective CFTR protein to the cell surface, which improves chloride ion transport and reduces mucus buildup in the lungs and other organs. It is approved for patients aged 6 years and older and paired with ivacaftor or with one responsive mutation, or in triple combination with elexacaftor and ivacaftor. It needs to be strictly genotype-tested before initiation because of the lack of efficacy in non-responsive CFTR profiles. Its common side effects include headache, upper respiratory tract infections (like runny or stuffy nose), abdominal pain, diarrhoea, rash, nasal congestion, etc.

The market for tezacaftor is driven by its usage in dominant cystic fibrosis (CF). Its utilisation in triple combinations, which covers most of the CF patients, contributes to its market growth. Its utilisation for providing superior lung function improvements and reduced exacerbations fuels its market.  Its usage in younger ages (down to 2 years), along with rising global cases of CF, makes it a popular option. Its efficacy leads to high adherence and physician preference, but high pricing pressures need negotiations that affect industrial tezacaftor procurement. The R&D towards next-gen modulators and gene therapies as competition, and geographic expansion into emerging markets, further impact its sourcing strategies.

Raw Material for Tezacaftor Production

According to the tezacaftor production plant project report, the key raw materials used in the production of tezacaftor include ethyl cyanoacetate, aryl bromide, fluoro-nitroaniline, R-glycidyl benzyl ether, propargyl alcohol, and benzyl chloromethyl ether.

Production Process of Tezacaftor

The extensive tezacaftor production cost report consists of the following major industrial production process:

1. From palladium-catalysed decarboxylative arylation: Tezacaftor synthesis starts with palladium-catalysed decarboxylative arylation of ethyl cyanoacetate with an aryl bromide to form a benzonitrile intermediate. This is followed by cyclopropanation via double alkylation with an ethylene fragment using a phase transfer catalyst, and then hydrolysis with recrystallisation to yield the carboxylic acid. The indole subunit is made by regioselective bromination of a fluoro-nitroaniline, epoxide opening with an R-glycidyl benzyl ether, nitro reduction to a hydroxy p-phenylenediamine salt. The Sonogashira coupling with a terminal alkyne, and the Larock cyclisation to produce the aminoindole. The terminal alkyne itself comes from converting propargyl alcohol to its chloride, forming a Grignard reagent, alkylating with benzyl chloromethyl ether, and desilylation. Finally, the acid is turned into an acid chloride and coupled with the aminoindole to form the bis-benzyl-protected product, which undergoes palladium-catalysed hydrogenation to deprotect and form tezacaftor as the final product.

Tezacaftor has the molecular formula of C26H27F3N2O6 with a molecular weight of 520.50 g/mol. It is a white to pale yellow crystalline solid or powder with low aqueous solubility. It has high permeability with a melting point between 180–185 degree Celsiuss. It has the logP value of 4.2–5.3, which makes it strongly lipophilic. It has the topological polar surface area of 92 Ų that supports oral bioavailability enhanced by fatty meals. It contains a stable cyclopropanecarboxamide core linking 2,2-difluorobenzo[d]dioxole and 6-fluoroindole moieties bearing dihydroxypropyl and hydroxymethyl groups. It has a 15-hour half-life and plasma protein binding greater than 99%.