Palovarotene is a selective retinoic acid receptor gamma agonist, under investigation as a potential treatment for fibrodysplasia ossificans progressiva, an ultra-rare and disabling genetic disease characterized by extra-skeletal bone formation in muscle and soft tissues. Palovarotene is being developed by Clementia Pharmaceuticals and was granted Fast Track and orphan drug designations by the United States Food and Drug Administration for the treatment of FOP and Orphan Medicinal Product Designation by the European Medicines Agency in 2014. Phase II clinical studies yielded positive results. Palovarotene is a retinoic acid receptor gamma agonist licensed to Clementia Pharmaceuticals from Roche Pharmaceuticals. At Roche, palovarotene was evaluated in more than 800 individuals including healthy volunteers and patients with chronic obstructive pulmonary disease. A one-year trial did not demonstrate a significant benefit on lung density in moderate-to-severe emphysema secondary to severe α-antitrypsin deficiency.
In 2011, animal studies demonstrated that RARγ agonists, including palovarotene, blocked new bone formation in both an injury-induced mouse model of heterotopic ossification and a genetically modified biological mouse model of FOP containing a continuously active ACVR1/ALK2 receptor in a dose-dependent manner. A 2016 study demonstrated that palovarotene inhibited spontaneous heterotopic ossification, maintained limb mobility and functioning, restored skeletal growth in FOP mouse models. Clementia Announces Plan to Submit a New Drug Application for Palovarotene for the Treatment of FOP Based on Positive Phase 2 Results. On the 6th of December 2019, Ipsen issued a partial clinical hold for patients under the age of 14. Due to reports of early fusion of growth plates. Ipsen acquired Clementia in 2019
Party Queen is the thirteenth full-length studio album by Japanese singer-songwriter Ayumi Hamasaki. The album was released digitally on March 14, 2012 and physically on March 21, 2012 through Avex Trax. A pop album, Party Queen is made up of dance songs and ballads; as with all of Hamasaki's albums, she wrote all of the lyrics. Composition was handled by a team of composers, as with many of her albums. Party Queen featured music songs recorded in London and was her second album to do so. Party Queen became Hamasaki's first album to feature no physical singles; as it lacked a physical release, "How Beautiful You Are" was ineligible to chart on the Oricon singles chart, but it did chart at number fifty-two on Billboard's Japan Hot 100, number three on the RIAJ Digital Track Chart. The song was certified Gold by the Recording Industry Association of Japan for digital sales exceeding 100,000. Party Queen received mixed reviews from music critics. Commercially, the album became her second to miss the Oricon's top position, debuting at number two in Japan with first-week sales of 97,691 copies, the lowest of her career at that time.
It received Gold certification. Party Queen became Hamasaki's last studio album to receive a certification. Party Queen was released in 5 different formats: CD only version. Only 2 songs had commercial endorsements prior to the album release: "Party Queen" was used as commercial song for Peach John and "How Beautiful You Are" was the theme song for drama show "Saigokara Nibanme no Koi", and the promotional music video for the single notably featured an appearance by late gay pornographic actor Koh Masaki and his boyfriend. To promote Party Queen after its release, Hamasaki attracted around 3,000 fans for her "Public Recording Session Event" at FM Osaka, held at Abeno Market Park Ceus Mall on March 27. After that, Hamasaki did Yahoo GyaO's live talk with Joshinavi. All lyrics are written by Ayumi Hamasaki