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iStock, hapabapa The regulator cited deficiencies at a third-party manufacturing facility. Camurus is seeking approval for its extended-release subcutaneous formulation of octreotide, which would allow more convenient once-monthly dosing for patients with acromegaly. The FDA has rejected Camurus’ investigational subcutaneous formulation of octreotide, dubbed CAM2029, for the treatment of the rare hormonal disorder acromegaly, the Swedish drugmaker announced on Tuesday. In a Complete Response Letter (CRL), the regulator cited “facility-related deficiencies” discovered last month during an inspection of a third-party manufacturer as the reason for the rejection and did not point to other issues, particularly as regards CAM2029’s clinical efficacy or safety data. The FDA needs to receive “satisfactory” responses from Camurus’ third-party provider before it can resolve the CRL, according to the company. CEO Fredrik Tiberg in a statement called the CRL “disappointing” but noted that the company remains “confident in the data supporting our [New Drug Application] and the potential of CAM2029 to address unmet medical needs of patients with acromegaly.” CRLs from the FDA rejecting drug candidates due to manufacturing issues are on the rise . Out of a total of 238 CRLs issued between 2017 and 2023, 30% involved quality/manufacturing issues —particularly problems with manufacturing processes, facility inspections, or chemical, manufacturing and controls. Camurus will work with its external manufacturer and with the FDA “to bring CAM2029 to patients living with acromegaly as soon as possible,” Tiberg said. To this end, the company said that it has already held labelling discussions with the regulator and that CAM2029’s prescribing information is “well advanced.” Afflicting around sixty patients per one million people, acromegaly is a rare and slowly progressive disease characterized by the abnormal growth of bones and enlarged hands, feet and facial features. Acromegaly also affects internal organs and can typically include symptoms such as headaches, joint pain and fatigue. Acromegaly is often caused by a tumor in the pituitary gland, which leads to the excess production of growth hormone and insulin growth factor-1. When uncontrolled, acromegaly worsens patients’ quality of life or can heighten their risk of death. Octreotide, the active ingredient of CAM2029, is a peptide drug that is well-known as an acromegaly therapy. It works by mimicking the function of somatostatin, a naturally occurring hormone, and activating its corresponding receptor. This mechanism of action helps suppress growth hormone, addressing the underlying cause of acromegaly. Octreotide also lowers the levels and activity of insulin and glucagon. The pharma industry has long taken advantage of octreotide’s therapeutic effects for acromegaly. Sun Pharmaceuticals won FDA approval for Bynfezia Pen (octreotide acetate) in 1988, which is indicated for the three-times-daily subcutaneous treatment of acromegaly. The drug is also approved for carcinoid tumors and vasoactive intestinal peptide tumors. Camurus’ investigational formulation is an extended-release version of octreotide that would allow for once-monthly dosing, giving patients a more convenient treatment option. In the Phase III ACROINNOVA 2 study, CAM2029 led to better biochemical control of acromegaly versus the current standard of care. Camurus’ injection also improved quality of life and symptom burden.

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.

This first-to-market launch showcases Teva’s proven strengths in complex generic formulations and enhances Teva’s strategic goal of sustaining a generic powerhouse.Octreotide acetate for injectable suspension is indicated to treat acromegaly and severe diarrhea for carcinoid syndrome. PARSIPPANY, N.J., Oct. 01, 2024 (GLOBE NEWSWIRE) -- Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), announced today the launch of the first and only generic version of Sandostatin®1 LAR Depot, in the United States. Octreotide acetate for injectable suspension (the generic version of Sandostatin® LAR Depot) is indicated to treat acromegaly and severe diarrhea for carcinoid syndrome. Please see the below for more information. “With today’s launch of octreotide acetate for injectable suspension (the generic version of Sandostatin® LAR Depot), Teva is providing patients a new option for this important treatment,” said Ernie Richardsen, SVP U.S. Commercial Generics.” He continued, “This first-to-market launch showcases Teva’s expertise in bringing complex generic formulations to market and demonstrates once again our ability to not only sustain a generics powerhouse, but also to bring value to patients and healthcare systems.” Sandostatin® LAR Depot had annual sales of $826 million as of July 2024, according to IQVIA data. What is octreotide acetate for injectable suspension (the generic version of Sandostatin® LAR Depot)?Octreotide acetate for injectable suspension (the generic version of Sandostatin® LAR Depot) is a prescription medication used in patients in whom initial treatment with octreotide acetate injection has been shown to be effective and tolerated for: Long-term maintenance therapy in acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy, is not an option to reduce GH and IGF-1 levels to normal.Long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.Long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors. In patients with carcinoid tumors and VIP-secreting tumors, the effect of octreotide acetate injection and octreotide acetate for injectable suspension on tumor size, rate of growth and development of metastases, has not been determined. IMPORTANT SAFETY INFORMATIONWhat is the most important information I should know about octreotide acetate for injectable suspension (the generic version of Sandostatin® LAR Depot)? Treatment with octreotide acetate for injectable suspension (the generic version of Sandostatin® LAR Depot) may affect gallbladder function, with reports of gallstones resulting in complications (inflammation of the gallbladder, bile duct, and pancreas, and requiring surgical removal of the gallbladder); sugar metabolism; thyroid and heart function; and nutritional absorption, which may require monitoring by your doctor. Tell your doctor if you experience signs or symptoms of gallstones or any of their complications.Patients with carcinoid tumors and VIP-secreting tumors should adhere closely to their scheduled return visits for reinjection in order to minimize exacerbation of symptoms. Patients with acromegaly should adhere to their return visit schedule to help assure steady control of GH and IGF-1 levels.What should I tell my doctor before taking octreotide acetate for injectable suspension (the generic version of Sandostatin® LAR Depot)? Tell your doctor if you have a history of heart disease or are taking other medications, including cyclosporine, insulin, oral hypoglycemic agents, beta-blockers, and bromocriptine.What are the possible side effects of octreotide acetate for injectable suspension (the generic version of Sandostatin® LAR Depot)? In acromegalic patients, the most common side effects of octreotide acetate for injectable suspension include gallstones, diarrhea, abdominal pain, gas, flu-like symptoms, constipation, headache, low red blood cells, injection-site pain, gallstones, high blood pressure, dizziness and fatigue.In carcinoid tumor and VIP-secreting tumor patients, the most common side effects of octreotide acetate for injectable suspension include back pain, fatigue, headache, abdominal pain, nausea, and dizziness.These are not all of the possible side effects of octreotide acetate for injectable suspension. Call your doctor for medical advice about side effects. You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. Please see the full Prescribing Information. About Teva Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a global pharmaceutical leader with a category-defying portfolio, harnessing our generics expertise and stepping up innovation to continue the momentum behind the discovery, delivery, and expanded development of modern medicine. For over 120 years, Teva's commitment to bettering health has never wavered. Today, the company’s global network of capabilities enables its ~37,000 employees across 58 markets to push the boundaries of scientific innovation and deliver quality medicines to help improve health outcomes of millions of patients every day. To learn more about how Teva is all in for better health, visit www.tevapharm.com. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe,” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to: the launch and commercial success of octreotide acetate for injectable suspension (the generic version of Sandostatin® LAR Depot); our ability to successfully compete in the marketplace, including: that we are substantially dependent on our generic products; concentration of our customer base and commercial alliances among our customers; delays in launches of new generic products; our ability to develop and commercialize biopharmaceutical products; our ability to achieve expected results from investments in our product pipeline; our ability to develop and commercialize additional pharmaceutical products; our ability to successfully execute our Pivot to Growth strategy, including to sustain and focus our portfolio of generics medicines; and other factors discussed in our Quarterly Report on Form 10-Q for the second quarter of 2024 and in our Annual Report on Form 10-K for the year ended December 31, 2023, including in the section captioned “Risk Factors.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements. 1 Sandostatin® LAR Depot is a registered trademark of Novartis AG. IR ContactsUnited StatesRan Meir(215) 591-8912 Sanjeev Sharma(973) 658 2700 PR ContactsUnited StatesKelley Dougherty(973) 658-0237 Yonatan Beker(973) 264 7378 IsraelEden Klein972 (3) 906-2645