CPLA2 (Cytosolic Phospholipase A2) Inhibitor AK106-001616

I had been interested in the CPLA2 (cytosolic phospholipase A2) inhibitor AK106-001616, when a study had been presented at the 2013 EULAR Annual Meeting. This year (2016) didn’t see any study being presented at the EULAR or ACR Annual Meetings. CPLA2 inhibition would also inhibit the downstream enzyme COX-2.

Last year there had been a study by T. Kozaki and colleagues, who looked of drug-drug interaction between the AK106-001616 and methotrexate in rheumatoid arthritis patients. The authors found a weak drug interaction between AK106-001616 and MTX, which is due to an altered MTX transport in renal proximal tubules.

K. Ohuchi and colleagues published a study on the protective effect of AK106-001616 on induced cell death in a murine motor neuron-like cell.

The NHS Health Research Authority reports a study in 2011: “A Phase IIa, Multi-Centre, Randomised, Double-Blind, Comparator Controlled, Repeated-Dose Study of 2 Dose Levels of AK106 001616 in Patients with Rheumatoid Arthritis”.

AdisInsight reports a phase 2 study for rheumatoid arthritis ongoing in Europe for 2015.

“To sum it up, I don’t see an important role of AK 106 in the treatment of RA patients.” Still!

Links:

http://rheumatologe.blogspot.de/2013/06/a-novel-cpla2-inhibitor-inhibits.html

Kozaki T, Tagashira M, Yamanishi K, Ellis B, Kayanoki T, Ooishi R, Sugiyama K, Matsuda S, Tsuruta K, Kohira T, Tsurui K.: Evaluation of drug-drug interaction between the novel cPLA2 inhibitor AK106-001616 and methotrexate in rheumatoid arthritis patients. Xenobiotica. 2015;45(7):615-24. doi: 10.3109/00498254.2014.1000430. Epub 2015 Jan 12. https://www.ncbi.nlm.nih.gov/pubmed/25579091

Ohuchi, K. , Tsuruma, K. , Shimazawa, M. , Nakamura, J. and Hara, H. (2016) The Novel cPLA2 Inhibitor AK106-001616 Has a Protective Effect on SOD1^G93A-Induced Cell Death in NSC34 Murine Motor Neuron-Like Cell. Pharmacology & Pharmacy, 7, 193-199. doi: 10.4236/pp.2016.75025.

http://www.hra.nhs.uk/news/research-summaries/study-of-2-dose-levels-of-ak106-001616-in-patients-with-ra/

http://adisinsight.springer.com/drugs/800030261

Buddhists are considered happy

Who would not bear in mind the Dalai Lama with a happy laugh on the face, if one was talking about Buddhism and happiness? It is believed that the serenity of the Buddhists is achieved by regular meditation through positive emotions.

But won’t we find this also in Christianity? The following line was found in the church song "Whoever leaves it to the care of God" [German: "Wer nur den lieben Gott läßt walten"] by Georg Neumarck from the year 1657: "Just keep a little quiet, and be happy in yourself" ["Man halte nur ein wenig stille / und sei doch in sich selbst vergnügt"].

In his 45th sermon "In omnibus requiem quaesivi" [English: In everything I sought rest], Meister Eckehart speaks of rest, silence, tranquility. All creation is in search of rest. Verses of the 24th chapter in the book Jesus Sirach are the basis for this sermon. "With them all I sought a place of rest, ..." (Sirach 24:7) Or: "In the city [Jerusalem] which he loves [God] as well as I, I found rest ..." (Sirach 24:11) This rest can be found in both testaments in many places, such as: "He said, my face will go with you and bring you to rest." (Exodus 33:14) "Better a handful of rest than both fists full of trouble and hardship after wind." (Sirach 4:6) "Come to me, all you troublesome and laden, and I will give you rest, take my yoke upon you, and learn from me, for I am meek and humble of heart, and ye shall find rest for your souls” (Matthew 11:28,29).

Han Shan (寒山) has become known in the West by Gary Snyder. The characters mean "Cold Mountain". He is a vagabond poet of the Tang (唐) period; and so it is not surprising that he was the godfather of Jack Kerouac's "The Dharma Bums". Han Shan wandered through the woods, laughed a lot, meditated in nature, and wrote poems on rocks and trees. He was closely associated with the Guo Qing Monastery / Temple (国清寺). The monastery dates back to the 6th century and still exists today. 300 poems by Han Shan have been handed down - but most Chinese poetry collections have 300 poems! “I am sitting quietly between the cliffs”, he writes in a poem.

The worst things that can happen to nowaday's people are a quiet place and an empty battery of the smartphone. But perhaps one does not need immediate enlightenment, but only a slow allowance of phases of rest. And then your stress falls off and you experience cheerful serenity and nevertheless are amused within yourself.

Possible Problems with Piosimilars

Sorry, I couldn’t resist the temptation. I’d like to talk about possible problems with biosimilars. I’ve just read the article on Medscape by Dr. Jonathan Kaye: “The March of the Biosimilars Continues”. In the U.S. the etanercept biosimilar Erelzi™, the adalimumab biosimilar Amjevita™, and the infliximab biosimilar Inflectra® are approved by the FDA. In Europe we already have more biosimilars: the infliximab biosimilars Remsima®, Inflectra®, and Flixabi®, whereof Remsima® and Inflectra® are bioidenticals. And we have the etanercept biosimilar Benepali®.

One problem will be changing from originator to one and even to a second biosimilar to fulfill biosimilar quota. I think this is a bad idea both for medical and legal reasons.

Another problem arises out of the number of originator biologics (already) and biosimilars. Rituximab biosimilars will follow soon. Have look at the IMS Infographic, there are 23 biosimilars are almost ready to be filed for approval. Rheumatologists will spend quite a lot of time with their patients and assistants or nurses to sort out, which product to use and how to avoid confusing one with the other.

But maybe I see more problems than solutions. And maybe I’d be better off with Padre Pio: “Pray, hope, and don't worry. Worry is useless. ...”

Links:

The March of the Biosimilars Continues - http://www.medscape.com/viewarticle/872592?nlid=111292_864&src=WNL_mdplsfeat_161213_mscpedit_rheu&uac=113211EX&spon=27&impID=1253065&faf=1

Bioidenticals - Biosimilars - Biologics – Biomimics -

http://rheumatologe.blogspot.de/2016/08/bioidenticals-biosimilars-biologics.html

IMS Infographic - http://medcitynews.com/2016/03/ims-report-what-biosimilars-are-in-the-pipeline/

https://www.goodreads.com/author/quotes/190385.Padre_Pio

Not so Wintry on the Southern Hemisphere

Frangipani

A fallen blossom, withering

Still smelling of youth

Jacaranda tree

Flamboyant with blue blossoms

But they fall like we

Blue starlings

Grabbing leftover chips

What a happy spring!

Soon after sunset

All cars must leave Etosha

Wilderness remains

Kalahari below

All is red dust

Just like myself

Southern moon

Shines upside down

Walking downside up

.