Sphingosine 1 phosphate

On 12 July, Biogen announced that it had entered a license and collaboration agreement with InnoCare Pharma for orelabrutinib, an oral small molecule Bruton’s tyrosine kinase inhibitor (BTKi) for the potential treatment of multiple sclerosis (MS). This collaboration will allow Biogen to expand its MS pipeline portfolio with a treatment that has a promising efficacy and safety profile, as well as the potential to cross the blood-brain barrier. Bruton’s tyrosine kinase (BTK) is an important protein in B cells, and the inhibition of BTK is thought to lead to B cell depletion and reduced B cell-mediated immune attacks in relapsing-remitting multiple sclerosis (RRMS) patients. B cell depletion is a well-received mechanism of action (MOA) in the treatment of MS, with a good efficacy and safety profile. The key benefit of BTKis is the fact that they offer a new MOA in this space. Orelabrutinib is a small molecule that seems to have effects on the microglia and B cells. Its MOA is distinct from that of the anti-CD20 monoclonal antibodies (mAbs), Roche’s Ocrevus (ocrelizumab) and Novartis’ Kesimpta (ofatumumab), as the drugs in this class do not cross the blood-brain barrier. If orelabrutinib does cross the blood-brain barrier, it may have more effects on the innate immune system and microglial activation. Over the past year, Biogen’s MS portfolio has been affected by the loss of patent protection and revenues for its blockbuster drug Tecfidera (dimethyl fumarate). Biogen reported sales of $3.84bn last year. GlobalData forecasts that Tecfidera will generate $1.12bn in 2026 due to generic competition. This decline in revenue is also due to the launch of second-generation sphingosine-1-phosphate (S1P) receptor modulators, specifically Novartis’ Mayzent (siponimod fumerate) in March 2019, Celgene’s Zeposia (ozanimod) last March, and Janssen’s Ponvory (ponesimod) this March. The launch of Biogen’s Vumerity (diroximel fumarate) alongside Roche’s Ocrevus, Novartis’ Kesimpta and other anti-CD20 mAb pipeline assets are expected to steal some of Tecfidera’s market share. This new collaboration agreement for orelabrutinib could once again establish Biogen as a strong player in the MS market. Orelabrutinib is currently marketed for different types of cancer in the US and China, and it is in Phase II of development for RRMS. It will not, however, have a first-in-class status, as another BTKi, Merck’s evobrutinib, is currently in Phase III of development. Evobrutinib is expected to launch in the US in 2025 and the five major European markets, namely France, Germany, Italy, Spain and the UK, in 2026. It will represent an additional choice for patients on B cell depletion therapies through its oral formulation, as all the other currently available B cell depletion therapies are injectables. GlobalData expects that evobrutinib will likely be positioned as a second-line treatment similar to other B cell depletion therapies such as Ocrevus and Kesympta. Orelabrutinib’s market share, however, could be limited due to its late entry in the MS market and its second-to-market status within its class. GlobalData expects evobrutinib to reach sales of $390m in 2028. Related Report Multiple Sclerosis – Global Drug Forecast and Market Analysis to 2028 Get the Report Latest report from Browse over 50,000 other reports on our store. Visit GlobalData Store Related Companies Kiskun Meridian Machine Manufacturing for the Pharmaceutical Industry Bioassay Analytical Services for Biological Assays Entecon Powder Handling and Conveying Solutions for Pharmaceutical Process Companies

photobyphm/Shutterstock Targeted radioligand therapy 177Lu-PSMA-617 from Novartis significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) in patients with PSMA-positive metastatic castration-resistant prostate cancer, according to findings from the Phase III VISION trial. Findings from this trial are promising, given that patients with castration-resistant prostate cancer often have tumors that show signs of growth despite receipt of testosterone-reducing hormone treatments. Patients with metastatic castration-resistant prostate cancer also have tumors that spread to other parts of the body and remain unresponsive to hormone therapy, making this investigational therapy a hopeful candidate for treatment of the disease. The five-year survival rate is approximately 15% for patients with metastatic castration-resistant prostate cancer, indicating this disease is an area where an urgent unmet treatment need exists. In the Phase III VISION trial, researchers examined the efficacy and safety of 177Lu-PSMA-617, an investigational PSMA-targeted radioligand therapy, in patients with advanced prostate cancer. The radioligand treatment approach from Novartis uses a targeting compound which can bind to markers expressed by tumors and a radioactive isotope. Ultimately, this causes DNA damage and inhibits tumor growth and further replication. Radioligand therapy supports targeted delivery of the radiation to the tumor, which can restrict damage to surrounding healthy tissue. The Phase III VISION trial achieved OS and rPFS endpoints, according to Novartis, and the safety of the drug was consistent with previously reported data. Full trial results are expected to be presented at a future medical meeting. The company also plans to submit the trial data to regulatory authorities in the U.S. and Europe. “Patients with metastatic castration-resistant prostate cancer have a less than 1 in 6 chance of surviving 5 years and need new treatment options,” said John Tsai, Novartis’s Head of Global Drug Development and Chief Medical Officer. “These groundbreaking data confirm our belief in the potential of 177Lu-PSMA-617 to reimagine outcomes for these patients through phenotypic precision medicine.” Other previous studies have examined the role of Novartis’ 177Lu-PSMA-617 in combination with other agents for the treatment of advanced prostate cancer. In late summer of last year, Noxopharm found that a combination of 177Lu-PSMA-617 and Veyonda®, a sphingosine-1-phosphate inhibitor, was associated with a median OS of 17.1 months in patients with late-stage prostate cancer who had not received benefit from all other standard treatment options. Another prior Phase I/II clinical trial from Noxopharm found the same combination provided a “striking” survival benefit in 56 patients with late-stage metastatic castration-resistant prostate cancer. The positive findings from other trials are good news for Novartis, which hopes to secure approval for 177Lu-PSMA-617 in advanced prostate cancer in the near future. In addition to its work in prostate cancer, Novartis recently announced it has joined the global fight against COVID-19 by lending its hand in helping companies’ manufacturer their novel coronavirus vaccines. The company said in a recent announcement that it is collaborating with Pfizer-BioNTech and CureVac to manufacture the two respective companies’ mRNA-based COVID-19 vaccines in Novartis facilities. The goal is to assist in ramping up manufacturing to meet the urgent global demand for effective and safe COVID-19 vaccines. “We are all working together with the vaccine developers to learn how to produce their vaccines rapidly,” said Joachim Momm, head of the Novartis manufacturing site in Stein, Switzerland. The Swiss site will help Pfizer-BioNTech produce its vaccine doses. “I hope we keep the collaborative spirit alive after the pandemic as well.”

After turning around Celgene’s S1P modulator for a long-awaited approval in multiple sclerosis, Bristol Myers Squibb is now trading in an FDA wildcard to get a quick review in ulcerative colitis. BMS has redeemed a priority review voucher for a speedy decision on its supplemental NDA for Zeposia, which hit the market this past June for MS. The FDA set a PDUFA date for May 30 — and if given the thumbs up, BMS says it would have the first oral sphingosine-1-phosphate (S1P) receptor modulator for UC. The submission was based on results from the Phase III True North study , in which Zeposia met both primary endpoints in adults with moderately to severely active UC: the proportion of patients in clinical remission based at week 10 in the induction phase, and at week 52 for the maintenance phase. Zeposia’s effect was highly statistically significant (p-value < 0.0001) the company said in June, adding that the drug also met key secondary endpoints. The overall safety profile was consistent with that of the already approved indication, BMS said in a statement. UC is a chronic inflammatory bowel disease characterized by an abnormal, prolonged immune response that creates long-lasting inflammation and ulcers in the lining of the large intestine. Zeposia works in MS by reducing the capacity of lymphocytes to exit lymph nodes, thus reducing the number of circulating lymphocytes in peripheral blood. While the mechanism of action in UC is still unclear, BMS thinks it may involve the reduction of lymphocyte migration into the inflamed intestinal mucosa, or lining. BMS snagged Zeposia when it bought out Celgene for $74 billion back in 2019. The drug, chemically known as ozanimod, had been sidelined after Celgene was flagged for lame conduct in filing a drug application. The FDA slapped Celgene with a refuse-to-file letter, concluding that the “nonclinical and clinical pharmacology sections in the NDA were insufficient to permit a complete review.” BMS flipped the drug around for an OK in March, making it the third oral S1P modulator approved for MS. The company held back on commercialization until June, due to the Covid-19 pandemic. Now time is of the essence, as they race for marketing approval in UC. Priority review vouchers are, in some ways, like a regulatory “I owe you”: They allow companies to have one of their drugs fast-tracked under the FDA’s priority review system. The idea of using a voucher system was first proposed as a way to incentivize the development of drugs for neglected tropical diseases. The first version was incorporated in the Food and Drug Administration Amendments Act (FDAAA) of 2007. Since then, guidance has been issued covering more indications, and allowing companies to buy and sell vouchers.