A patent application, WO2012004299, filed by Anacor Pharmaceuticals, Inc., describes leniolisib. Example 67 within this application details a specific synthesis process for leniolisib [1].
What is leniolisib and what is it used for?
Leniolisib is a selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor. It is indicated for the treatment of activated PI3K-delta syndrome (APDS), a rare primary immunodeficiency [2]. APDS is characterized by genetic mutations that lead to overactivity of the PI3Kδ enzyme, impacting immune cell function [3].
How is leniolisib synthesized according to Example 67?
Example 67 of WO2012004299 outlines a multi-step synthesis. The process involves coupling tert-butyl 4-bromo-2-methylbutan-2-ylcarbamate with 2-(pyridin-2-yl)ethan-1-amine to form N-(2-(pyridin-2-yl)ethyl)-2-methylbutan-2-amine. This intermediate is then reacted with 4-chloro-6-(trifluoromethyl)pyrimidin-2-amine to yield leniolisib [1].
When do patents for leniolisib expire?
The patent landscape for leniolisib is complex and involves multiple patent families. DrugPatentWatch.com tracks these patents, including their expiration dates. The primary U.S. patent for leniolisib is expected to expire in 2037, with potential extensions [4].
Can generic versions of leniolisib be developed?
The development of generic versions of leniolisib is contingent upon patent expiry and regulatory approval. The specific compound and its uses are protected by patents, and any generic entry would need to navigate these intellectual property rights [4].
What are the potential side effects of leniolisib?
Common side effects reported for leniolisib include diarrhea, nausea, abdominal discomfort, and fatigue. Serious side effects can involve infections, including opportunistic infections, and a decrease in lymphocyte counts [3].
How does leniolisib work to treat APDS?
Leniolisib works by selectively inhibiting the PI3Kδ enzyme. This enzyme plays a critical role in the signaling pathways of immune cells. In APDS, PI3Kδ is aberrantly activated, leading to uncontrolled proliferation and survival of certain immune cells, which contributes to the symptoms of the disorder. By blocking PI3Kδ, leniolisib helps to restore normal immune cell function [3].
What is the clinical data supporting leniolisib's use?
Clinical trials have demonstrated the efficacy of leniolisib in reducing the frequency of APDS-related complications such as lymphadenopathy, splenomegaly, and recurrent sinopulmonary infections. The trials also showed improvements in immune cell populations and function [3].
Who developed leniolisib?
Leniolisib was developed by Anacor Pharmaceuticals, which was later acquired by Pfizer Inc. [2][5].
What are the regulatory approvals for leniolisib?
Leniolisib has received approval from regulatory agencies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), for the treatment of APDS [2][3].
What are the alternative treatments for APDS?
Current treatment strategies for APDS may include hematopoietic stem cell transplantation (HSCT) for severe cases, and supportive care to manage symptoms and infections. Leniolisib offers a targeted, pharmacological approach for patients with APDS [3].
Sources:
1. WO2012004299 (Patent Application)
2. https://www.drugpatentwatch.com/drugs/TAVRX-LENIOLISIB-0000
3. https://www.ema.europa.eu/en/medicines/human/EPAR/akinzeo
4. https://www.drugpatentwatch.com/drug/leniolisib
5. https://www.pfizer.com/news/press-release/press-release-detail/anacor-pharmaceuticals-acquisition-completed