Drugs in Focus The early bird catches the worm! Selection of novel, still patented APIs for development activities in patent free countries

Transcription

1 Drugs in Focus The early bird catches the worm! Selection of novel, still patented APIs for development activities in patent free countries Searching for patent circumventing manufacturing processes, polymorphic forms and salts Products supported by EU-DMFs, TPs and other appropriate documents Value added Co-Developments /28 - Version FA_Journal

2 Drugs in Focus The early bird catches the worm! Fingolimod HCL Deferasirox Aprepitant Febuxostat Lacosamide TP available Paliperidone Abiraterone acetate Apixaban Cinacalcet HCL /28 - Version FA_Journal

3 Drugs in Focus The early bird catches the worm! Dabigatran etexilate Darifenacin HBR Ivabradine HCL Pitavastatin calcium Posaconazole Prasugrel HCL Solifenacin succinate Tigecycline /28 - Version FA_Journal

4 Fingolimod HCL Fingolimod (trade name GILENYA) is an immuno- modulating drug, approved for treating multiple sclerosis. It has reduced the rate of relapses in relapsing-remitting multiple sclerosis by over half. Fingolimod is a sphingosine 1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction. On September 22, 2010, Fingolimod became the first oral diseasemodifying drug approved by the Food and Drug Administration to reduce relapses and delay disability progression in patients with relapsing forms of multiple sclerosis. Novartis announced on March 10, 2011 that it had received a notice of compliance from Health Canada and that the drug would be available April 1, 2011 at pharmacies. On March 17, 2011, the European Medicines Agency approved the drug for use in the European Union. Formula: C 19H 33NO 2 HCL CAS-No.: Indication field: Immunosuppressive agent Innovator: Novartis Innovators brand: GILENYA Approval date: 21. September 2010 Form: capsule; oral Pack sizes: 0.5 mg /28 - Version FA_Journal

5 Deferasirox Deferasirox (marketed as EXJADE) is a rationally-designed oral iron chelator, developed by Novartis. Its main use is to reduce chronic iron overload in patients who are receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. It is the first oral medication approved in the USA for this purpose. It was approved by the United States Food and Drug Administration (FDA) in November According to FDA (May 2007), renal failure and cytopenias have been reported in patients receiving Deferasirox oral suspension tablets. It is approved in the European Union by the European Medicines Agency (EMA) for children 6 years and older for chronic iron overload from repeated blood transfusions. Formula: C 21H 15N 3O 4 CAS-No.: Indication field: Iron chelator Innovator: Novartis Innovators brand: EXJADE Approval date: 2. November 2005 Form: tablet for suspension; oral Pack sizes: 125 mg; 250 mg; 500 mg /28 - Version FA_Journal

6 Aprepitant Aprepitant (brand name EMEND) is an antiemetic chemical compound that belongs to a class of drugs called substance Pantagonists (SPA). It mediates its effect by blocking the neurokinin 1 (NK1) receptor. Aprepitant is manufactured by Merck & Co. under the brand name EMEND for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting. It was approved by the FDA in Aprepitant may also be useful in the treatment of cyclic vomiting syndrome & late-stage chemotherapy induced vomiting, but there are few studies to date. On January 2008, the FDA approved Fosaprepitant, an intravenous form of Aprepitant, which is to be sold under the tradename EMEND Injection in the US and as IVEMEND in some other countries. Formula: C 23H 21N 4O 3 CAS-No.: Indication field: Anticancer Innovator: Merck & Co. Innovators brand: EMEND Approval date: 26. March 2003 Form: capsule; oral Pack sizes: 40 mg; 80 mg; 125 mg /28 - Version FA_Journal

7 Febuxostat Febuxostat (trade names ADENURIC in Europe and New Zealand, FEBURIC in Japan and Takeda's ULORIC in the US) is a urate lowering drug, an inhibitor of xanthine oxidase that is indicated for use in the treatment of hyperuricemia and chronic gout. Febuxostat received marketing approval by the European Medicines Agency on April 21, 2008 and was approved by the U.S. Food and Drug Administration on February 16, A study comparing Febuxostat to Allopurinol found that more individuals treated with Febuxostat had decreased levels of uric acid, but there was no difference in the amount of initial gout flares or the surface area of gout tophi. Formula: C 16H 16N 2O 3S CAS-No.: Indication field: Antigout preparation Innovator: Takeda Pharms USA Innovators brand: ULORIC (US) / ADENURIC (EU) Approval date: 13. February 2009 Form: tablet; oral Pack sizes: 40 mg; 80 mg /28 - Version FA_Journal

8 Lacosamide Lacosamide (formerly known as Erlosamide, Harkeroside, SPM 927, or ADD ) is a medication developed by Union Chimique Belge (UCB) for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain marketed under the trade name VIMPAT. The U.S. Food and Drug Administration (FDA) accepted UCB's New Drug Application for Lacosamide as of November 29, 2007, beginning the approval process for the drug. UCB also filed for marketing approval in the European Union (EU); the European Medicines Agency accepted the marketing application for review in May The drug was approved in the EU on September 3, It was approved in the US on October 29, Lacosamide release was delayed owing to an objection its placement into schedule V of the Controlled Substances Act. The FDA issued their final rule of placement into Schedule V on June 22, Formula: C 13H 18N 2O 3 CAS-No.: Indication field: Antiepileptic Innovator: UCB Inc. Innovators brand: VIMPAT Approval date: 28. October 2008 Form: solution; intravenous/oral tablet; oral Pack sizes: 10 ml; 20 ml/ 10 ml 50 mg; 100 mg; 150 mg; 200 mg /28 - Version FA_Journal

9 Paliperidone Paliperidone (trade name INVEGA), also known as 9- hydroxyrisperidone, is a dopamine antagonist and 5-HT2A antagonist of the atypical antipsychotic class of medications. It is developed by Janssen Pharmaceutica. INVEGA is an extended release formulation of Paliperidone that uses the OROS extended release system to allow for once-daily dosing. Paliperidone palmitate (trade name INVEGA SUSTENNA, named XEPLION in Europe and other countries) is a long-acting injectable formulation of Paliperidone palmitoyl ester indicated for once-monthly injection after an initial titration period. Paliperidone is used to treat mania and at lower doses as maintenance for bipolar disorder. It is also used for schizophrenia and schizoaffective disorder. Formula: C 23H 27FN 4O 3 CAS-No.: Indication field: Antipsychotic Innovator: Janssen Pharms Innovators brand: INVEGA Approval date: 31. July 2009 Form: suspension, extended release; intramuscular Pack sizes: 39 mg/0.25 ml; 78 mg/0.5 ml; 117 mg/0.75 ml; 156 mg/1 ml; 234 mg/1.5 ml /28 - Version FA_Journal

10 Abiraterone acetate Abiraterone is a drug used in combination with Prednisone in metastatic castration-resistant prostate cancer (formerly hormoneresistant or hormone-refractory prostate cancer) -- i.e., prostate cancer not responding to androgen deprivation or treatment with antiandrogens. It is formulated as the prodrug Abiraterone acetate and marketed under the trade name ZYTIGA. After an expedited six-month review, Abiraterone was approved by the U.S. Food and Drug Administration (FDA) in April In Phase III trials, it extended median survival to 14.8 months versus 10.9 months placebo, and the trial was stopped because of the successful outcome. Formula: C 26H 33NO 2 CAS-No.: Indication field: Steroid Innovator: Janssen Biotech Innovators brand: ZYTIGA Approval date: 05. September 2011 Form: tablet; oral Pack sizes: 250 mg /28 - Version FA_Journal

11 Apixaban Apixaban (BMS , tradename ELIQUIS) is an anticoagulant for the treatment of venous thromboembolic events. It is a direct factor Xa inhibitor. Apixaban has been available in Europe since May In the United States, it is undergoing phase III trials for the prevention of venous thromboembolism. An FDA decision on Apixaban which was expected on June 28, 2012 was delayed. It is being developed in a joint venture by Pfizer and Bristol-Myers Squibb. Formula: C 25H 25N 5O 4 CAS-No.: Indication field: Platelet Inhibitor Innovator: Pfizer & Bristol Myers Squibb Innovators brand: ELIQUIS Approval date: May 2012 Form: tablet; oral Pack sizes: 2,5 mg, 5 mg /28 - Version FA_Journal

12 Cinacalcet HCL Cinacalcet is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues) by allosteric activation of the calciumsensing receptor that is expressed in various human organ tissues. It is sold by Amgen under the trade name SENSIPAR in North America and Australia and as MIMPARA in Europe. Cinacalcet is used to treat secondary hyperparathyroidism (elevated parathyroid hormone levels), a consequence of end-stage renal disease. Cinacalcet is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma. Formula: C 22H 23CIF 3N HCL CAS-No.: Indication field: Thyroid Dysfunction Innovator: Amgen Innovators brand: SENSIPAR (US) / MIMPARA (EU) Approval date: 22. October 2004 Form: tablet; oral Pack sizes: 30 mg base; 60 mg; 90 mg /28 - Version FA_Journal

13 Dabigatran etexilate Dabigatran (PRADAXA in Australia, Europe and USA, PRADAX in Canada, PRAZAXA in Japan) is an oral anticoagulant from the class of the direct thrombin inhibitors. It is being studied for various clinical indications and in some cases it offers an alternative to Warfarin as the preferred orally administered anticoagulant ("blood thinner") since it does not require frequent blood tests for international normalized ratio (INR) monitoring while offering similar results in terms of efficacy. There is no specific way to reverse the anticoagulant effect of Dabigatran in the event of a major bleeding event,unlike Warfarin, although a potential Dabigatran antidote (Darucizumab) is undergoing clinical studies. It was developed by the pharmaceutical company Boehringer Ingelheim. Formula: C 34H 41N 7O 5 CAS-No.: Indication field: Platelet Inhibitor Innovator: Boehringer-Ingelheim Innovators brand: PRADAXA Approval date: 18. March 2008 Form: capsule oral Pack sizes: 75 mg; 150 mg /28 - Version FA_Journal

14 Darifenacin HBR Darifenacin (trade name ENABLEX in US and Canada, EMSELEX in Europe) is used to treat people who have urinary problems such as urinary incontinence, urinary urgency or urinary frequency which are caused by an overactive bladder. It works by preventing spasms of the bladder muscle. This can help to reduce the episodes of urinary incontinence, the frequency of urination or reduce the feeling of urgency that bladderspasms can cause. It was discovered by scientists at the Pfizer research site in Sandwich, UK under the identifier UK-88,525 and previously was marketed by Novartis; however in 2010 US rights for were sold to Warner Chilcott. Formula: C 28H 30N 2O 2 HBR CAS-No.: Indication field: Urological preparation Innovator: Novartis Innovators brand: ENABLEX (US) / EMSELEX (EU) Approval date: 22. October 2004 Form: tablet, extended release; oral Pack sizes: 7,5 mg; 15 mg /28 - Version FA_Journal

15 Ivabradine HCL Ivabradine is a novel medication used for the symptomatic management of stable angina pectoris. It is marketed by Servier under the trade names PROCORALAN (worldwide), CORALAN (in Hong Kong, Singapore, Australia and some other countries), CORLENTOR (in Armenia, Spain, Italy and Romania) and CORAXAN (in Russia and Serbia). It is also marketed in India under the brand names IVABID and BRADIA. During its development, Ivabradine was known as S Ivabradine acts by reducing the heart rate via specific inhibition of the funny channel, a mechanism different from beta blockers and calcium channel blockers, two commonly prescribed antianginal drugs. Ivabradine is a cardiotonic agent. Formula: C 27H 36N 2O 5 HCL CAS-No.: Indication field: Cardiovascular disease Innovator: Servier Innovators brand: PROCORALAN Approval date: 25. October 2005 Form: tablet; oral Pack sizes: 5 mg; 7 mg /28 - Version FA_Journal

16 Pitavastatin calcium Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering medication class of statins, marketed in the United States under the trade name LIVALO. Like other statins, it is an inhibitor of HMG-CoA reductase, the enzyme that catalyses the first step of cholesterol synthesis. It has been available in Japan since 2003, and is being marketed under licence in South Korea and in India. It is likely that Pitavastatin will be approved for use in hypercholesterolaemia (elevated levels of cholesterol in the blood) and for the prevention of cardiovascular disease outside South and Southeast Asia as well. In the US, it received FDA approval in Formula: C 50H 46CaF 2N 2O 8 CAS-No.: Indication field: Cholesterol & Triglycerine reducer Innovator: Kowa Co Innovators brand: LIVALO Approval date: 3. August 2009 Form: tablet; oral Pack sizes: 1 mg; 2 mg; 4 mg /28 - Version FA_Journal

17 Posaconazole Posaconazole is a triazole antifungal drug marketed in the United States, the European Union, and in other countries by Schering-Plough under the trade name NOXAFIL. In Canada, Posaconazole is marketed by Schering-Plough under the trade name POSANOL. Posaconazole works by disrupting the close packing of acyl chains of phospholipids, impairing the functions of certain membrane-bound enzyme systems such as ATPase and enzymes of the electron transport system, thus inhibiting growth of the fungi. It does this by blocking the synthesis of ergosterol by inhibiting of the enzyme Lanosterol 14α-demethylase and accumulation of methylated sterol precursors. Posaconazole is significantly more potent at inhibiting 14-alpha demethylase than Itraconazole. Formula: C 37H 42F 2N 8O 4 CAS-No.: Indication field: Antifungal Innovator: Schering-Plough Innovators brand: NOXAFIL Approval date: 25. October 2005 Form: suspension; oral Pack sizes: 40 mg/ml /28 - Version FA_Journal

18 Prasugrel HCL Prasugrel (marketing name EFFIENT in the US and India, and EFIENT in the EU) is a platelet inhibitor developed by Daiichi Sankyo Co. and produced by Ube and currently marketed in the United States in cooperation with Eli Lilly for acute coronary syndromes planned for percutaneous coronary intervention (PCI). Prasugrel was approved for use in Europe in February 2009, and is currently available in the UK. On July 10, 2009, the US Food and Drug Administration approved the use of Prasugrel for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome who are to be managed with PCI. Formula: C 20H 20FNO 3S HCL CAS-No.: Indication field: Platelet Inhibitor Innovator: Ube & Eli Lilly Innovators brand: EFFIENT (US) / EFIENT (EU) Approval date: 23. February 2009 Form: tablet; oral Pack sizes: 5 mg; 10 mg /28 - Version FA_Journal

19 Solifenacin succinate Solifenacin (trade name VESICARE) is a medicine of the antimuscarinic class and was developed for treating contraction of overactive bladder with urge incontinence. It is manufactured and marketed by Astellas, Teva Pharmaceutical Industries and GlaxoSmithKline Solifenacin is a competitive cholinergic receptor antagonist. The binding of acetylcholine to these receptors, particularly the M 3 receptor subtype, plays a critical role in the contraction of smooth muscle. By preventing the binding of acetylcholine to these receptors, Solifenacin reduces smooth muscle tone in the bladder, allowing the bladder to retain larger volumes of urine and reducing the number of micturition, urgency and incontinence episodes. Because of a long elimination half life, a once-a-day dose can offer 24 hour control of the urinary bladder smooth muscle tone. Formula: C 23H 26N 2O 2 C 4H 6O 4 CAS-No.: Indication field: Urological preparation Innovator: Astellas Innovators brand: VESICARE Approval date: 19. November 2004 Form: tablet; oral Pack sizes: 5 mg; 10 mg /28 - Version FA_Journal

20 Tigecycline Tigecycline is a glycylcycline antibiotic marketed by Wyeth under the brand name TYGACIL. It was given a U.S. Food and Drug Administration (FDA) fast-track approval and was approved on June 17, It was developed in response to the growing prevalence of antibiotic resistance in bacteria such as Staphylococcus aureus and Acinetobacter baumannii. The New Delhi metallo-β-lactamase multidrug-resistant Enterobacteriaceae has also shown susceptibility to Tigecycline. Formula: C 29H 39N 5O 8 CAS-No.: Indication field: Antibiotic Innovator: Wyeth Innovators brand: TYGACIL Approval date: 15. June 2005 Form: injectable; infusion Pack sizes: 50 mg/vial /28 - Version FA_Journal

21 Drugs in Focus The early bird catches the worm! Gliptins (novel class of oral anti-diabetic agents for treatment of diabetes mellitus type 2) Sitagliptin Vildagliptin Saxagliptin TP available Linagliptin TP available Alogliptin /28 - Version FA_Journal

22 Drugs in Focus The early bird catches the worm! Gliptins (novel class of oral anti-diabetic agents for treatment of diabetes mellitus type 2) We offer Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), also known as Gliptins. Gliptins are a class of oral hypoglycemics that block DPP-4. They can be used to treat diabetes mellitus type 2. Type 2 diabetes is a chronic metabolic disease that can be caused by pancreas dysfunction, deficiency in insulin secretion, insulin resistance and/or increased hepatic glucose production. It is one of the fastest growing health concerns in the world. Products belonging to this class are: -Sitagliptin (FDA approved 2006, marketed by Merck & Co. as JANUVIA) -Vildagliptin (EU approved 2007, marketed in EU by Novartis as GALVUS) -Saxagliptin (FDA approved 2009, marketed by Bristol Myers Squibb & AstraZeneca as ONGLYZA) -Linagliptin (FDA approved 2011, marketed by Eli Lilly & Boehringer Ingelheim as TRAJENTA) -Alogliptin (FDA approved 2013, marketed by Takeda as NESINA) /28 - Version FA_Journal

23 Sitagliptin phosphate Sitagliptin (Ipreviously identified as MK-0431 and marketed as the phosphate salt under the trade name JANUVIA) is an oral antihyperglycemic of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. It was developed, and is marketed, by Merck & Co. This enzymeinhibiting drug is used either alone or in combination with other oral antihyperglycemic agents (such as Metformin or a Thiazolidinedione) for treatment of diabetes mellitus type 2. The benefit of this medicine is its fewer side effects (e.g., less hypoglycemia, less weight gain) in the control of blood glucose values. Formula: C 16H 15F 6N 5O H 3PO 4 H 2O CAS-No.: Innovator: Merck & Co. Innovators brand: JANUVIA Approval date: 16. October 2006 Form: tablet; oral Pack sizes: 25mg; 50mg; 100mg /28 - Version FA_Journal

24 Vildagliptin Vildagliptin (previously LAF237, trade names GALVUS, ZOMELIS, JALRA) is an oral anti-hyperglycemic agent of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of Langerhans in the pancreas. Vildagliptin has been shown to reduce hyperglycemia in type 2 diabetes mellitus. Vildagliptin is an unique molecule with dual nature as it manages the glucagon levels in hypoglycemia as well as hyperglycemia. Formula: C 17H 25N 3O 2 CAS-No.: Innovator: Novartis Innovators brand: GALVUS Approval date: 26. September 2007 Form: tablet; oral Pack sizes: 50mg /28 - Version FA_Journal

25 Saxagliptin HCL Saxagliptin (previously identified as BMS ) is a new oral hypoglycemic of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Early development was solely by Bristol-Myers Squibb; in 2007 AstraZeneca joined with Bristol-Myers Squibb to co-develop the Bristol-Myers Squibb final compound and collaborate on the marketing of the drug. In June 2008, it was announced that ONGLYZA would be the trade name under which Saxagliptin will be marketed. In February 2014, the U.S. FDA announced they were investigating possible cardiac morbidity risk, based on in an article in the New England Journal. That article concluded "DPP-4 inhibition with Saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although Saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes." Formula: C 18H 25N 3O 2 HCL CAS-No.: Innovator: BMS & AstraZeneca Innovators brand: ONGLYZA Approval date: 31. July 2009 Form: tablet; oral Pack sizes: 2.5mg; 5mg /28 - Version FA_Journal

26 Linagliptin Linagliptin (BI-1356, trade names TRADJENTA (US) and TRAJENTA (worldwide)) is a DPP-4 inhibitor developed by Boehringer Ingelheim (being marketed in collaboration with Eli Lilly) for treatment of type II diabetes and approved by the U.S. Food and Drug Administration (FDA) on 2 May It works by increasing the amounts of certain natural substances that lower blood sugar when it is high. Linagliptin is not used to treat type 1 diabetes (condition in which the body does not produce insulin and, therefore, cannot control the amount of sugar in the blood) or diabetic ketoacidosis (a serious condition that may develop if high blood sugar is not treated). Linagliptin used in combination with insulin to treat diabetes has not been studied to date. Results in 2010 from a Phase III clinical trial of Linagliptin showed that the drug can effectively reduce blood sugar. Formula: C 25H 28N 8O 2 CAS-No.: Innovator: Eli Lilly & Boehringer Ingelheim Innovators brand: TRADJENTA (US) / TRAJENTA (EU) Approval date: 02. May 2011 Form: tablet; oral Pack sizes: 5mg /28 - Version FA_Journal

27 Alogliptin benzoate Alogliptin (trade name NESINA in the US and VIPIDIA in Europe) is an orally administered anti-diabetic drug in the DPP-4 inhibitorclass, developed by Syrrx, a company which was acquired by Takeda Pharmaceutical Company in Like other medications for the treatment of Type 2 diabetes, Alogliptin does not decrease the risk of heart attack and stroke. Like other members of the Gliptin class, it causes little or no weight gain, exhibits relatively little risk of causing hypoglycemia, and exhibits relatively modest glucose-lowering activity. Alogliptin and other Gliptins are commonly used in combination with Metformin in patients whose diabetes cannot adequately be controlled with Metformin alone. Formula: C 18H 21N 5O 2 C 7H 6O 2 CAS-No.: Innovator: Takeda Innovators brand: NESINA (US) / VIPIDIA (EU) Approval date: 25. January 2013 Form: tablet; oral Pack sizes: 6.25mg; 12.5mg; 25mg /28 - Version FA_Journal

28 We can be your partner of first choice for new development projects. Our team is ready to assist you right from the beginning with all necessary documents for registration purposes. For your specific product inquiries please do not hesitate to contact us: F. & A. PHARMA-Handels-GmbH Bonhoefferring 41 D Dorsten GERMANY Phone: +49 (0) Fax: +49 (0) info@fa-pharma.com Web: You will also benefit from contacting F. & A. PHARMA /28 - Version FA_Journal