Vibegron

Upperton Pharma will move from R&D to GMP production and commercialisation on a single site. Credit: Upperton Limited. UK-based contract development and manufacturing organisation (CDMO) Upperton Pharma Solutions has received approval from the UK Medicines and Healthcare products Regulatory Agency (MHRA) for its facility in Nottingham. The approval, granted following an MHRA inspection, marks the expansion of the company’s capabilities at this newly commissioned 50,000ft² development and GMP [good manufacturing practices] facility. Upperton Pharma completed the construction, commissioning, validation and approval process for the unit within 18 months. The CDMO will develop oral, nasal and pulmonary drug assets, offering Phase I, II, and III clinical supplies. Upperton Pharma will move from research and development (R&D) to GMP production and commercialisation on a single site. See Also: MHRA approves Pierre Fabre’s vibegron to treat OAB Rusan Pharma’s API Plant in Ankleshwar Receives US FDA GMP Approval The facility’s recent investment in large-scale process equipment, including a Gerteis mini-pactor, a GEA post-hoist blender, an O’Hara M50 tablet coating system and a ZANASI 40 capsule filler, will aid Upperton Pharma in handling batch sizes up to 250kg. Its capability covers a broad range of dosage forms such as liquids, solids, semi-solids and inhaled pharmaceuticals, including potent molecules and controlled drugs. With 24 years of experience, Upperton Pharma provides early drug development solutions to clients worldwide. The company has formulation and analytical development laboratories, GMP manufacturing and quality control testing capabilities. It is licensed by the MHRA for manufacturing clinical trial material supplies. It also has expertise in spray drying, a technique used to address challenges with poorly soluble molecules, and as a particle engineering technology for targeted pulmonary and nasal drug product deposition. Upperton Pharma Solutions CEO Nikki Whitfield stated: “We are absolutely delighted to achieve this milestone. “We have been conducting manufacturing scale-up activities since the start of the year following the installation of the larger-scale solid oral dosage form process trains and this gives the green light for our GMP facility to support clients right through to late-phase clinical manufacture and product registration.”

Revolution Medicines headquarters in Redwood City, California. Credit: Tada Images via Shutterstock. Revolution Medicine plans to kickstart a Phase III trial following positive data from a first-in-human study of its investigational KRAS inhibitor RMC-6236 in pancreatic cancer patients. In an investor deck released yesterday [15 July], the company outlined updated data from the Phase I trial (NCT05379985) that outlined responses from 127 patients with pancreatic ductal carcinoma (PDAC) who received between a dose of RMC-6236 ranging from 160mg to 300mg. Median progression-free survival was 8.1 months in patients with the KRAS G12X mutation, and 7.6 months in those who broadly have RAS-mutant tumours. Among participants who had at least three prior treatment regimens, the median progression-free survival was 4.2 months. Out of the 127 participants, 96% suffered from side effects. The most common were rashes, diarrhoea, nausea, and mouth sores. Those adverse events were deemed severe or medically significant in 28% of patients. The company had previously presented early Phase I data, which covered 40 evaluable patients, at the European Society of Medical Oncology 2023 meeting in October. See Also: MHRA approves Pierre Fabre’s vibegron to treat OAB Rusan Pharma’s API Plant in Ankleshwar Receives US FDA GMP Approval The Redwood City, California-based company now plans on initiating a Phase III RASolute 302 trial in metastatic PDAC patients. The study will compare the 300mg dose of RMC-6236 to the investigator’s choice of standard chemotherapy among patients previously treated with two lines of therapy. According to Revolution, primary endpoint data is expected in 2026 and 2027. KRAS is a gene that provides instructions for making a protein called K-Ras, which is part of the RAS/MAPK pathway. It is the most frequently mutated oncogene, meaning KRAS has been a target investigated by cancer scientists for decades. There are currently only two approved KRAS inhibitors, Bristol Myers Squibb ’s (BMS) Krazati (adagrasib) and Amgen ’s Lumakras (sotorasib), both of which are KRAS G12C inhibitors indicated to treat NSCLC. Their US Food and Drug Administration (FDA) approvals were a breakthrough for the scientific community, with GlobalData forecasting sales of $1.63bn for Krazati and $787m for Lumakras in 2030. GlobalData is the parent company of Pharmaceutical Technology. In its 1Q earnings released in May, the company outlined plans to release data in H2 2024 to support the initiation of two pivotal studies in pancreatic cancer and NSCLC. Though KRAS G12C is a prominent mutation seen in lung cancer, certain malignancies such as pancreatic cancer most commonly have the G12D mutation in the KRAS gene. Therefore, there is a need for KRAS inhibitors that can treat other cancer types. GMC-6236 is part of the emerging innovation being seen in the KRAS space. Instead of targeting a specific mutation such as G12C, the drug is a multi-selective non-covalent inhibitor designed to treat patients with cancers driven by a wide range of common RAS mutations. Other companies advancing KRAS inhibitors include GenFleet Therapeutics, which is investigating the Phase III asset GFH925 , a KRAS G12C inhibitor for the treatment of patients with refractory metastatic colorectal cancer (CRC).