Leniolisib Production Cost Reports

The report provides a detailed analysis essential for establishing a Leniolisib production plant. It encompasses all critical aspects necessary for Leniolisib production, including the cost of Leniolisib production, Leniolisib plant cost, Leniolisib production costs, and the overall Leniolisib production plant cost. Additionally, the study covers specific expenditures associated with setting up and operating a Leniolisib 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.

Leniolisib is an oral, small-molecule drug approved primarily for treating activated phosphoinositide 3-kinase delta syndrome (APDS), a rare genetic immunodeficiency disorder caused by mutations that lead to overactive PI3Kδ enzyme. By selectively inhibiting PI3Kδ, leniolisib helps normalise immune system function, reduces lymphoproliferation, and restores the balance of key immune cells such as B and T lymphocytes. Its industrial application is focused on pharmaceutical production and clinical use for APDS patients aged 12 and older, with ongoing investigations for potential use in other immune-related conditions like primary Sjögren's syndrome. The drug is recognised as a targeted precision therapy in rare immune diseases, marking a significant advancement in the treatment of ultra-rare immunodeficiencies.

The market demand for leniolisib is driven by its status as the first and only approved targeted treatment for activated phosphoinositide 3-kinase delta syndrome (APDS), a rare and progressive primary immunodeficiency with significant unmet medical needs. Expanding its indication to younger paediatric patients aged 4 to 11 years and ongoing clinical trials in even younger children enhance the market potential. The rarity of APDS, combined with its serious clinical manifestations such as immune dysregulation, recurrent infections, and risk of lymphoma, boosts the demand for effective therapies like leniolisib. Additionally, leniolisib's positive clinical trial results showing improved immune function and safety profile support its adoption and market growth.

The drug's niche but critical application in a rare disease market with limited treatment options drives its commercial prospects. Its status as a prescription drug for the rare condition activated phosphoinositide 3-kinase delta syndrome (APDS) entails stringent regulatory approvals and compliance requirements, impacting availability and supply. Additionally, contractual obligations such as licensing agreements with Novartis and milestone-related payments impact commercial industrial leniolisib procurement practices.

Raw Material for Leniolisib Production

According to the Leniolisib production plant project report, the various raw materials for Leniolisib production include 6-benzyl-4-chloro-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine and (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate.

Production Process of Leniolisib

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

1. Production via chemical synthesis: The production process of leniolisib starts with 6-benzyl-4-chloro-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine, which is coupled with (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate in the presence of triethylamine at 120 degree Celsius for 42 hours, yielding the first intermediate. The benzyl protecting group is then removed using 20% palladium hydroxide on carbon and ammonium formate in methanol at 65 degree Celsius for 2 hours, giving another intermediate compound. The compound is further coupled with 5-bromo-2-methoxy-3-(trifluoromethyl)pyridine using sodium tert-butoxide, tris(dibenzylideneacetone)dipalladium(0), and 2-di-t-butylphosphino-2'-(N,N-dimethylamino)biphenyl in tert-butanol at 100 degree Celsius for 5 hours, producing the final intermediate. Finally, the Boc protecting group is deprotected with DCM/TFA, and the resulting compound is coupled with propionyl chloride in the presence of sodium bicarbonate in DCM at room temperature for 1 hour, yielding leniolisib.

Properties of Leniolisib

Leniolisib is a white to yellowish powder with the molecular formula C21H25F3N6O2 for the free base and molecular weight around 450.47 g/mol, while the phosphate salt form weighs about 548.46 g/mol. It has a topological polar surface area of 83.5 Ų, with one hydrogen bond donor and eight hydrogen bond acceptors, and five rotatable bonds. Its chemical name is 1-[(3S)-3-[[5,6,7,8-Tetrahydro-6-[6-methoxy-5-(trifluoromethyl)-3-pyridinyl]pyrido[4,3-d]pyrimidin-4-yl]amino]-1-pyrrolidinyl]-1-propanone phosphate. Leniolisib is orally bioavailable and known for poor water solubility, which affects its pharmacokinetics. It undergoes metabolic transformations, including O-demethylation and N-dealkylation, producing several metabolites. The drug's pharmacological activity is as a selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor used in immunotherapy.