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Nov 11, 2013

New Diabetes Drugs Moving Through the Pipeline

Some feature more patient-friendly delivery methods.

New Diabetes Drugs Moving Through the Pipeline

Each entry includes the name of the drug candidate; the sponsor and any collaboration partners involved; method of action; indication; Phase III trials; and other information where applicable. [© Radu Razvan - Fotolia.com]

  • Fasiglifam (TAK-875)

    Sponsor/Developer: Takeda

    Mechanism of action: G-protein-coupled receptor (GPCR) 40 agonist

    Indication: Type 2 diabetes

    Phase III trial(s): Phase III, CCT-003 trial—Positive results presented at the 56th Annual Meeting of the Japan Diabetes Society in May; 24-week study assessing the efficacy and safety of once-daily fasiglifam 25 mg and 50 mg in 192 Japanese patients with type 2 diabetes. Statistically significant reduction in HbA1c was found in patients treated with fasiglifam 25 mg (-0.75) and fasiglifam 50 mg (-1.01) compared to placebo.

  • FIAsp (NN1218)

    Sponsor/Developer: Novo Nordisk

    Mechanism of action: Faster-acting formulation of insulin aspart (marketed as NovoLog® in the U.S., and NovoRapid® in the rest of the world).

    Indication: Type 1 and 2 diabetes

    Phase III “onset” trials: Three trials launched in August, the company disclosed October 31 in its third-quarter results:

    • Assessing efficacy and safety of faster-acting insulin aspart compared to insulin aspart in combination with basal insulin in 1,100 people with type 1 diabetes for 52 weeks;
    • Assessing efficacy and safety of faster-acting insulin aspart compared to insulin aspart in combination with basal insulin in 670 people with type 2 diabetes for 26 weeks; and
    • Comparing faster-acting insulin aspart used as part of a basal-bolus regimen with basal insulin treatment for 18 weeks in 220 people with type 2 diabetes.
  • Forxiga™ (dapagliflozin)

    Sponsor/Developer: Bristol-Myers Squibb and AstraZeneca

    Mechanism of action: SGLT2 inhibitor

    Indication: Once-daily tablets for adults with type 2 diabetes

    Regulatory review status:

    • Awaiting decision by FDA on its NDA resubmission, accepted for review by the agency in July. The Prescription Drug User Fee Act action date is January 11, 2014. FDA requested submission of additional clinical trial data in October 2012 when it postponed a decision on the original NDA, filed March 2011; FDA Endocrinologic and Metabolic Drugs Advisory Committee recommended against approval, July 2011. The complete response letter was issued January 2012.
    • Marketed in the EU, where it was approved last year as a once-daily oral medication for adults with type 2 diabetes—the first SGLT2 drug to gain such approval.
    • Awaiting decisions by China’s State Food and Drug Administration and Japan’s Ministry of Health, Labour and Welfare on regulatory submissions.

    Phase III trial(s): In September, at the EASD annual meeting, the company and its partner, AstraZeneca, announced positive results from a Phase III study evaluating dapagliflozin in adults with type 2 diabetes who were inadequately controlled on combination treatment with metformin plus sulfonylurea. Patients treated with dapagliflozin 10 mg as an add-on therapy to metformin plus sulfonylurea showed significant improvements in HbA1c and significant reductions in fasting plasma glucose and in body weight compared to placebo at 24 weeks. Significant improvements were also observed in seated systolic blood pressure at eight weeks in patients treated with dapagliflozin compared to placebo.

    Line extensions—As of August 1, AstraZeneca listed in Phase III several line extensions of Forxiga: a Forxiga/metformin fixed-dose combination; Forxiga as an add on to DPP-4; Forxiga as an add-on to insulin and add-on to metformin, long-term data; Forxiga in patients with high CV risk, studies 18 and 19, long-term data; Forxiga as triple therapy with metformin and a sulfonylurea; and Forxiga-DECLARE outcomes study, with an estimated filing date of 2020.

  • IDegLira (NN9068)

    Sponsor/Developer: Novo Nordisk

    Mechanism of action: Combination of Tresiba® (insulin degludec), a once-daily new-generation basal insulin analog; and Victoza® (liraglutide), a once-daily human GLP-1 analogue

    Indication: Type 2 diabetes

    Regulatory review status: Awaiting decision on marketing authorization application submitted in June to European Union.

    Phase III trial(s):

    • Phase IIIa, DUal Action of Liraglutide and Insulin Degludec in Type 2 Diabetes (DUAL) I trial—Positive results detailed September 27 at 49th Annual European Association for the Study of Diabetes (EASD) Congress from 26-week trial comparing the efficacy and safety of IDegLira, in people with type 2 diabetes inadequately controlled with metformin with or without pioglitazone. Patients treated once daily with IDegLira showed an HbA1c reduction of 1.9% (from baseline of 8.3%), achieving primary endpoints of superiority versus liraglutide and noninferiority versus insulin degludec, with no weight gain and a low rate of hypoglycemia compared to insulin degludec in adults with type 2 diabetes.
    • Phase IIIa; DUAL II trial—Positive results announced December 19, 2012, of 26-week trial comparing IDegLira and Tresiba®, in addition to metformin, in people with type 2 diabetes who were previously inadequately controlled on basal insulin in combination with 1–2 oral antidiabetic agents. Patients treated once daily with IDegLira showed an HbA1c reduction of 1.9% (from baseline of 8.7%), meeting the primary endpoint of superiority compared to stand-alone therapy with Tresiba. IDegLira patients also experienced a weight loss of approximately 2.5 kg (5.5 pounds).
  • Invokana (canagliflozin)

    Sponsor/Developer: Johnson & Johnson (Janssen Research & Development); licensed from Mitsubishi Tanabe Pharma for North America, South America, Europe, the Middle East, Africa, Australia, New Zealand, and parts of Asia

    Mechanism of action: SGLT2 inhibitor

    Indication: Once-daily tablets for adults with type 2 diabetes

    Regulatory review status:

    • U.S.—Approved by FDA in March, two months after the agency’s Endocrinologic and Metabolic Drugs Advisory Committee voted 10–5 to recommend approval of the drug. That approval came with a requirement of five post-marketing studies: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the Pediatric Research Equity Act, including a pharmacokinetic and pharmacodynamic study, and a safety and efficacy study.
    • EU—Invokana won a positive opinion in September from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP), removing a key hurdle to marketing approval for the drug by the European Commission.

    Phase III trial(s): Clinical program enrolled 10,285 patients in nine studies assessing Invokana at 100 mg and 300 mg once-daily doses in placebo- and active comparator-controlled studies, as well as three large studies in special populations: older patients, patients with moderate renal impairment, and patients who had or were at risk for cardiovascular disease. Results showed that in addition to improvements in glycemic control, both doses of canagliflozin were associated with weight loss and reductions in blood pressure across clinical studies.

  • Ipragliflozin L-proline (ASP1941)

    Sponsor/Developer: Astellas, MSD, and Kotobuki Pharmaceutical

    Mechanism of action: SGLT2 inhibitor

    Indication: Type 2 diabetes

    Regulatory review status:

    • Japan—Awaiting decision from Ministry of Health, Labour and Welfare on market authorization application filed in March. Astellas agreed to manufacture and sell ipragliflozin, and co-promote the drug in Japan with MSD and Kotobuki Pharmaceutical, with which Astellas discovered the compound in a research collaboration.
    • U.S. and EU—Development has been discontinued “after comprehensive consideration of intensified competition for this product, and the prioritization in our pipeline,” Astellas said in its annual report for the year that ended March 31.

    Phase III trial(s): Astellas said it conducted six Phase III studies to investigate the safety and efficacy of ipragliflozin, both as a monotherapy and in combination with six other hypoglycemic agents for a long-term period. According to Astellas, these studies confirmed the drug’s effectiveness and favorable safety, in combination with other hypoglycemic agents.

  • Luseogliflozin hydrate (TS-071)

    Sponsor/Developer: Taisho Pharmaceutical

    Mechanism of action: SGLT2 inhibitor

    Indication: Once-daily for type 2 diabetes

    Phase III trial(s): Five Phase III clinical trials in Japan, targeting 1,310 type 2 diabetes patient. Positive results of two trials were presented at the 49th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona:

    • In a study of 158 Japanese patients with type 2 diabetes who received either 2.5 mg of luseogliflozin or a placebo orally once daily for 24 weeks, luseogliflozin significantly reduced hemoglobin A1c (HbA1c), the study’s primary endpoint. At the time of completing drug administration, the difference between the HbA1c reduction from the baseline and the placebo was -0.75%.
    • In a study of 299 Japanese patients with type 2 diabetes receiving 2.5 mg of luseogliflozin orally once-daily for 52 weeks (a dosage was increased to 5 mg when glycemic control was insufficient), luseogliflozin significantly reduced the level of HbA1c, the study’s primary endpoint. HbA1c reduction from the baseline was -0.50%. Among both studies’ secondary endpoints, according to Taisho, luseogliflozin significantly improved postprandial blood glucose levels two hours after meals and fasting blood glucose levels, while also significantly lowering body weight and abdominal circumference.
  • LixiLan (lixisenatide+ insulin glargine)

    Sponsor/Developer: Sanofi; lixisenatide licensed from Zealand Pharma

    Mechanism of action: Combination of GLP-1 agonist (Lyxumia or lixisenatide) and basal insulin analog (Lantus® or insulin glargine)

    Indication: Type 2 diabetes

    Phase III trial(s): Set to launch in the first half of 2014. Sanofi is evaluating both a Fix-Flex device allowing for flexible Lantus dosing combined with a fixed lixisenatide dose, as well as a Fixed-Ratio device in Phase IIb. Positive results were announced from clinical studies of “free combination” lixisenatide and Lantus in about 1,250 patients, according to Zealand Pharma. Sanofi lists the drug in its Phase II pipeline, according to Sanofi’s Early Stage Pipeline Pharma & Vaccines, as of August 2013.



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