Somatostatin

Taylor Tieden for BioSpace The FDA is looking at four events for the remainder of October, one of which is an advisory committee meeting for a dual SGLT inhibitor for use alongside insulin in type 1 diabetes and chronic kidney disease. This month seems to be a relatively slow one for the FDA, which has only a handful of catalysts coming up, including target action dates for a KRAS inhibitor and a UTI drug. Read below for more. Amgen Seeks Colorectal Cancer Approval for Lumakras By October 17, the FDA is expected to release its decision on Amgen ’s application for Lumakras (sotorasib) in combination with Vectibix (panitumumab) for the treatment of metastatic colorectal cancer. The application is backed by the CodeBreaK 300 study, which tested the combination regimen against the investigator’s choice of therapy. A total of 160 patients were enrolled into the study, according to its clinicaltrials.gov page , all of whom carried the KRAS G12C mutation. The FDA gave Amgen’s application its Priority Review designation. In August 2023, Amgen announced that Lumakras plus Vectibix aced the primary endpoint in CodeBreak 300, demonstrating a significant improvement in progression-free survival versus current standard of care. Additional data from the study were reported at the 2024 American Society of Clinical Oncology annual meeting in June, showing a trend toward better overall survival in patients treated with Amgen’s drug combo. Lumakras is a small molecule inhibitor of G12C-mutated KRAS , which is involved in the hyperactive cell division seen in cancer. It keeps mutated KRAS in an inactive state and helps prevent unchecked tumor growth while also prompting cell death. The drug was first approved for non-small cell lung cancer under the FDA’s accelerated pathway in May 2021, but its full approval was denied in December 2023 , with the regulator asking for an additional confirmatory study. Camurus Proposes Subcutaneous Octreotide for Acromegaly Swedish biotech Camurus is seeking approval for its investigational subcutaneous injection of octreotide for the once-monthly treatment of acromegaly, a hormonal disorder that causes abnormal bone and tissue growth. The FDA has until October 21 to release its verdict . Octreotide is a peptide drug that has long been approved for acromegaly. Bynfezia Pen (octreotide acetate), for instance, was approved for subcutaneous treatment in 1988 and is also indicated for other diseases, such as diarrhea associated with metastatic carcinoid tumors or vasoactive intestinal peptide tumors. According to Bynfezia’s label , octreotide works by mimicking the effects of the natural hormone somatostatin, exerting a strong inhibitory effect on other hormones, such as glucagon and insulin. Octreotide also blocks the action of growth hormone, which in acromegaly is present in high amounts. Camurus’ subcutaneous formulation of octreotide, dubbed CAM2029, allows for better exposure to the drug and enables a more convenient once-monthly dosing schedule. Bynfezia, by comparison, is given three times a day for acromegaly. CAM2029 also comes as a pre-filled injection pen to allow self-administration. The drug application is backed by the Phase III ACROINNOVA 2 study, which enrolled 135 patients who either had biochemically controlled disease or who had uncontrolled disease but were on stable doses of standard-of-care therapy. Results showed that CAM2029 led to better biochemical control of acromegaly versus standard of care, alongside improvements in symptom burden and quality of life. Iterum Advances Oral UTI Drug for Women The FDA is reviewing Iterum Therapeutics’ New Drug Application (NDA) for sulopenem etzadroxil/probenecid, also called oral sulopenem, for the treatment of uncomplicated urinary tract infection (uUTI) in women. The regulator is expected to release its verdict by October 25. Oral sulopenem is backed by findings from the Phase III REASSURE study. According to a topline readout in January 2024, oral sulopenem matched oral Augmentin (amoxicillin/clavulanate) in terms of overall response, the study’s primary endpoint. Additionally, overall success, which takes into account clinical and microbiological outcomes, was statistically better in the oral sulopenem group than in Augmentin comparators. Last month, the FDA’s Antimicrobial Drugs Advisory Committee met to discuss Iterum’s application. While the panel of external experts was not asked to vote on any specific matter, Iterum found the discussion to be encouraging for oral sulopenem’s regulatory prospects. The experts, said CEO Corey Fishman, “acknowledged oral sulopenem as an important treatment option for certain patients with uUTI and agree that the appropriate use of oral sulopenem by treating physicians is critical to limiting antimicrobial resistance.” The FDA had previously rejected oral sulopenem in uUTI, noting in July 2021 that Iterum needed to provide additional clinical data to support an approval. After Previous Rejection, Lexicon’s Insulin Adjunct to Face Adcomm To close out the month, the FDA will convene its Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) On October 31 to discuss Lexicon Pharmaceuticals’ Zynquista (sotagliflozin), which the biotech is proposing as an adjunctive therapy to insulin to control blood glucose levels in patients with type 1 diabetes and chronic kidney disease (CKD). Zynquista’s active ingredient sotagliflozin works by inhibiting the SGLT2 and SGLT1 proteins, which are involved in the absorption of glucose in the kidneys and gastrointestinal tract, respectively. Lexicon first sought type 1 diabetes approval for sotagliflozin in 2018, backing its application with data from the inTandem clinical program, which includes three Phase III trials with around 3,000 patients enrolled. In January 2019, however, the EMDAC was split regarding sotagliflozin’s approvability, with half of the panelists voting against it, citing the risk of diabetic ketoacidosis and other safety issues. Months later, in March 2019, the FDA rebuffed Lexicon’s regulatory bid . Lexicon appealed the FDA’s verdict, though this has since stalled. The biotech refiled its NDA in June 2024, with CEO Lonnel Coats at the time reiterating that the company is “confident in the benefit/risk pro sotagliflozon” for type 1 diabetes and CKD.

Acromegaly is a rare condition where patients develop a benign tumor in the pituitary gland that secretes excess growth hormone, which in turn leads the liver to overproduce the hormone IGF-1. For patients that cannot have surgery, the standard of care for acromegaly is a monthly injection of peptide analogs of somatostatin to reduce the production of growth hormone. These treatments, which consist of depots of octreotide, lanreotide or pasireotide, are injected with a large needle and can be a burdensome therapy for patients. Crinetics’ trial, named PATHFNDR-1 enrolled patients with acromegaly to test the potential of the company’s small molecule drug paltusotine, a once-per-day oral alternative to hormone injections. The patients were originally receiving depot somatostatin analog injections and were switched to either paltusotine or a placebo during the trial. According to the results, 83% of patients given paltusotine were able to keep their IGF-1 levels from going too high, compared to just 4% in the placebo group, meeting the trial’s primary goal. The trial also met all secondary goals, such as symptom severity and change from baseline in IGF-1 level, and paltusotine was well tolerated. “We designed paltusotine to be the preferred therapeutic option for people living with acromegaly,” said Scott Struthers, founder and chief executive officer of Crinetics, in a public statement. “We could not be more excited by the results from PATHFNDR-1, which further reinforce our conviction that, if approved, paltusotine could address patients’ unmet need for a simple, oral, once-daily therapy.” googletag.cmd.push(function () { googletag.display('text-ad1'); }); He added that the company expects to apply for market approval of paltusotine when it completes its second phase 3 trial in acromegaly next year. In parallel, Crinetics is testing paltusotine in a phase 2 trial in patients with carcinoid syndrome. Another clinical-stage candidate in Crinetics’ pipeline is in phase 1/2 testing to evaluate it for the treatment of the conditions Cushing’s disease and congenital adrenal hyperplasia. A twice-daily oral form of octreotide called Mycapssa was approved by the FDA in 2020, making it the first oral somatostatin analog for the treatment of acromegaly. Nonetheless, if paltusotine is approved, its once-per-day dosing could help the small molecule drug to stand out in the market.