Cerebroside sulfatase

The FDA approval for Daiichi Sankyo's Vanflyta, a protein degrader deal between Astellas and PeptiDream, and a Takeda trial flop made our news this week. Daiichi Sankyo's FLT3 inhibitor overcame FDA rejection to win an approval. Astellas signed another protein degrader deal, this time with PeptiDream. Takeda's enzyme replacement therapy flunked a mid-stage trial in a rare neurological disorder. And more. 1. After FDA snub, Daiichi's Vanflyta gains US approval and tees up AML clash with Novartis, Astellas About four years after an initial FDA rejection, Daiichi Sankyo has finally won approval for its FLT3 inhibitor quizatinib as a treatment for acute myeloid leukemia. Now marketed as Vanflyta, the Daiichi drug will compete against Astellas’ Xospata and Novartis’ Rydapt. Vanflyta’s label only covers cancers with FLT3-ITD mutations, while its rivals' approvals cover any FLT3 mutations. 2. Astellas notches another protein degrader pact with $21M upfront for PeptiDream Astellas has put down 3 billion yen ($21 million) up front to tap PeptiDream’s peptide discovery platform to develop protein degraders. PeptiDream will also be in line for potential milestone payments up to 20.6 billion yen ($145 million) per target, plus single-digit percentage sales royalties. Astellas has previously inked protein degrader deals with Cullgen and Fimecs. 3. Takeda suffers setback as promising neuroscience prospect flunks phase 2 Takeda’s TAK-611, an enzyme replacement therapy proposed for the rare genetic disease metachromatic leukodystrophy, has failed in a mid-stage trial. The phase 2 trial didn’t meet primary or secondary endpoints, according to Takeda. The readout was listed as a potential inflection point for Takeda’s late-stage neuroscience programs for this fiscal year. 4. Takeda hypes up dengue vaccine launch progress as Vyvanse generics loom Takeda is touting the progress of its dengue vaccine Qdenga despite a recent decision to pull its application in the U.S. The company is now focused on some endemic markets, which make up about 80% to 85% of the vaccine’s peak sales projection of $1.6 billion to $2 billion, CEO Christophe Weber said on a confererence call. Takeda is getting closer to having end-to-end in-house production capability for Qdenga by 2025, he said. 5. Lawmakers propose federal database to track supply chain vulnerabilities Sen. Gary Peters (D-MI), chair of the Homeland Security and Governmental Affairs Committee, has teamed with Republican Sens. James Lankford (R-OK) and Mike Braun (R-IN) to introduce a bill to create a federal database to track supply chain vulnerabilities. The Mapping America’s Pharmaceutical Supply Act would catalog the origin of each drug, quantities available and the location of their manufacturing facilities. 6. Centaur Pharmaceuticals slapped with FDA warning letter outlining quality, cleaning lapses Centaur Pharmaceuticals’ drug ingredient plant in Maharashtra, India, got an FDA warning letter with two observations about quality deficiencies and lapses in cleaning protocols. The agency is demanding Centaur completely assess its documentation systems and manufacturing standards training program. Other News of Note 7. AstraZeneca enlists SK Chemicals to produce diabetes combo drug Sidapvia 8. India’s pharma exports continue to rise despite manufacturing scandals, trade body says (Reuters)

Pictured: Takeda sign at its office in California/iStock, JHVEPhoto Takeda’s investigational enzyme replacement therapy TAK-611 did not meet its primary and secondary endpoints in a Phase II trial, the company revealed Thursday during its first quarter earnings report for fiscal year 2023. The Japanese multinational is currently conducting further analysis of the data and is looking at all possible options for TAK-611, “but given these outcomes, the program unfortunately is likely to be discontinued,” Andy Plump, Takeda’s president of R&D, said in an investor call Thursday. Designed to be administered intrathecally, TAK-611 is a recombinant human arylsulfatase A enzyme replacement therapy. The candidate is being developed for metachromatic leukodystrophy (MLD), a rare genetic lysosomal storage disease characterized by a pathogenic build-up of lipids in cells, particularly in the nervous system, which lead to the progressive loss of organ function. MLD is commonly caused by mutations on the gene that encodes for the arylsulfatase A enzyme, which under healthy conditions is crucial for the breakdown of these lipids. TAK-611 had previously earned the Japanese Ministry of Health, Labor and Welfare’s Orphan Drug Designation. Takeda’s neuroscience group was supposed to take charge of TAK-611’s development starting in the first quarter of fiscal year 2023, though the candidate’s future now remains uncertain. As in the case of TAK-611, the prospects of Takeda’s oral EGFR inhibitor Exkivity (mobocertinib) in non-small cell lung cancer are now unclear. In the most recent quarter, the Phase III EXCLAIM-2 trial, which pitted Exkivity monotherapy against chemotherapy as a first-line treatment option, was stopped for futility. The company will discuss the best next steps for the program with regulators. Takeda’s dengue vaccine TAK-003 also suffered a setback during the first fiscal quarter, when the Japanese pharma voluntarily withdrew its Biologics License Application after the FDA sought additional data that fell beyond the scope of the Phase III trial it ran for the candidate. TAK-003 is approved in other countries, such as the UK, Thailand and Brazil, where it is sold under the brand name Qdenga. Despite these headwinds, however, Takeda’s performance exceeded analyst expectations. The company posted total revenue of approximately $7.6 billion, representing an 8.9% increase from the same period the year before. Its operating profits came in at $1.2 billion, a 12% improvement from last year. Takeda maintained its full-year revenue forecast of around $27.6 billion and expects a low-single-digit percent decline. Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.