S&P’s top ten promising drugs of 2009-2010

Denosumab, Brilinta, Effient & Afinitor among S&P list of 10 most promising drugs

Amgen’s Denosumab, AstraZeneca’ Brilinta (AZD6140) and Onglyza, BMS’ Belatacept, Eli Lilly’s Effient, King Pharmaceuticals’s Embeda/Remoxy, Merck’s Cordaptive, Novartis’ Afinitor, Novo Nordisk’s Liraglutide and Sanofi-Aventis’ Multaq are the top ten most promising late-stage drugs due out over the next two years, according to a list compiled by Standard & Poor rating agency. 

Standard & Poor says these drugs become very important for the drug makers as several of the revenue spinners are nearing patent expiry in the 2-3 years. In 2010-2012, a record amount of drug sales will lose patent protection in the U.S and be exposed to generic competition including Pfizer’s Lipitor, Bristol-Myers Squibb’s Plavix and Avapro, Eli Lilly’s Zyprexa, Wyeth’s Effexor, and Merck’s Cozaar/Hyzaar and Singulair.

Standard & Poor besides listing the ten most prospective drugs selected from a wide range of companies, from top-rated Big Pharma and biotechnology companies to smaller speculative-grade specialty pharmaceutical players, explains how these drugs are crucial to their respective makers 

(1) Denosumab Osteoporosis drug from Amgen

Denosumab is a human monoclonal antibody to treat osteoporosis. Deosumab is receptor-activator for Nuclear Factor k B Ligand (RANKL), an important molecule in bone metabolism that acts as the primary signal in bone resorption while treating osteoporosis. Amgen has completed Phase III clinical trials for the osteoporosis treatment with Denosumab and prevention of osteoporosis in post menopausal women and in the treatment of treatment-induced bone loss in breast and prostate cancer patients and received positive results.

Data from Phase III clinical trials of Denosumab for the prevention of bone metastases in prostate cancer patients and skeletal-related events in breast cancer, prostate cancer, and solid tumors will be available in late 2009 and in 2010. The twice-yearly Denosumab dosing for the prevention of fractures in patients with osteoporosis makes it likely that the compliance rate would be higher than the current daily or weekly forms of treatment. 

Denosumab was filed for approval of to the U.S. Food & Drug Administration in December 2008. Amgen expects osteoporosis drug denosumab will be in markets in late 2009. Amgen’s top products—Aranesp, Epogen, Neulasta/Neupogen, and Enbrel—contribute more than 90% of its sales so far.

2) Brilinta (AZD6140) drug to treat arterial thrombosis from AstraZeneca

Brilinta is an anti-platelet agent to treat arterial thrombosis. Brilinta is also the first reversible oral adenosine diphosphate (ADP) receptor antagonist to prevent more thrombotic events than do currently available thienopyridine therapies in patients afflicted with acute coronary system (ACS). The 11,000-patient trial PLATO has completed recruitment with data on arterial thrombosis treatment to be available in mid-2009. The molecule’s reversibility is the key differentiator from competing products Plavix and prasugrel. Brilinta, which is currently in Phase III of clinical development, will be launched in the fourth quarter of 2009 in Europe and the US. AstraZeneca faces some high-profile patent expirations for existing blockbuster drugs—Casodex in 2009, Arimidex in 2010, and Nexium in 2009-10.

 (3) Onglyza (Saxagliptin) to treat type-2 diabetes from (AstraZeneca & Bristol-Myers Squibb

Onglyza is a dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type-2 diabetes. Onglyza will be the third DPP-4 inhibitor after Januvia and Galvus, which is still awaiting FDA approval. Type-2 diabetes drug Onglyza has been submitted for regulatory approval in Europe and the US. AstraZeneca and BMS, await a decision around midyear 2009. The FDA’s advisory committee gave a positive recommendation for type-2 diabetes drug Onglyza, on Apr. 2, 2009, supporting the molecule’s new drug application for the treatment of adults with type 2 diabetes. 

(4) Belatacept to treat organ-transplant rejection from Bristol-Myers Squibb

Belatacept is a fusion protein linked to CTLA-4 that selectively blocks the T-cell activation process. Belatacept is designed to reduce organ-transplant rejection with fewer side effects than cyclosporine, the current gold standard in immunosuppressant therapy. Belatacept is currently in late-stage Phase III, with FDA filing expected this year. Belatacept has fast-track approval status. 

(5) Effient (Prasugrel) platelet inhibitor from Eli Lilly

Prasugrel is a platelet inhibitor. Prasugrel belongs to the thienopyridine class of ADP receptor inhibitors, the same class as Bristol-Myers’ Plavix, the leading anti-platelet inhibitor and one of the world’s largest-selling drugs. Data released from Lilly’s Phase III Triton clinical study, comparing Effient with Plavix, showed that Effient was more potent at reducing the number of heart attacks—but also that it caused increased bleeding incidents. An FDA advisory committee recently voted 9 to 0 to approve Effient for heart attack patients undergoing percutaneous coronary intervention. Effient could reach the market by the end of 2009. 

Effient platelet inhibitor is developed by Lilly and Daiichi Sankyo. Lilly loses patent protection on its top drugs in the 2010-12 period—specifically, top product Zyprexa (2011). Eli Lilly will also lose patent protection: Gemzar (for cancer) in 2013; Humalog (for diabetes) in 2013; Evista (for osteoporosis) in 2013; and Cymbalta (for depression) in 2014. 

(6) Embeda/Remoxy (Morphine/Oxycodone) pain treatment from King Pharmaceuticals 

Embeda is an abuse-resistant, extended-release, morphine-based drug for moderate to severe pain. Embeda is a follow-on product to Kadian, which was divested as part of King’s acquisition of Alpharma. A sequestered naltrexone hydrochloride inner core is designed to mitigate euphoric effects of the morphine upon tampering. Remoxy is an abuse-resistant, extended-release oxycodone-based drug to treat moderate-to-severe pain. Its dosage form and gel-like consistency resist “dose-dumping” and unapproved routes of administration to prevent abuse.  Remoxy pain drug received an approval from FDA in November 2008. However, an FDA panel suggested Remoxy be labeled tamper-resistant, rather than abuse-resistant. King filed a new drug application (NDA) for Embeda. King recently bought Alpharma for approximately $1.6 billion. The approval of one or both therapies would greatly enhance King’s (KG) presence in the $20 billion pain management market. 

(7) Cordaptive atherosclerosis drug from Merck

Cordaptive is a treatment for atherosclerosis. Coradaptive is a combination of extended-release niacin with laropiprant. Laropiprant is a chemical that prevents the side effects of niacin, such as flushing and hot flashes. Cordaptive is a cholesterol-lowering medication that reduces LDL-cholesterol, raises HDL-cholesterol, and reduces triglyceride levels. Cordaptive is already approved to treat atherosclerosis in Europe. But Cordaptive received a nonapprovable letter from the FDA in April 2008. Merck faces patent expirations on Cozaar/Hyzaar in 2010 and Sigulair in 2012. Merck recently decided to acquire Schering-Plough for $41 billion. 

(8) Afinitor (Everolimus) kidney cancer treatment drug from Novartis 

Afinitor is an oral treatment for kidney cancer. Afinitor is an inhibitor of the mTOR pathway for patients with advanced kidney cancer. The drug could be the first therapy to demonstrate significant benefit for patients after standard kidney cancer treatment fails. Novartis received FDA approval for Afinitor on Mar. 30, 2009, as a first treatment for patients with advanced kidney cancer after failure of either Sutent or Nexavar-based treatments. Other future filings of the molecule are likely for neuroendocrine tumors, lymphoma, hepatocarcinoma, and gastric, non-small cell lung and breast cancer, which are all in Phase III development. 

(9) Liraglutide to treat diabetes, obesity from Novo Nordisk 

Liraglutide targets diabetes and obesity segments. Liraglutide is a once-daily glucagon-like peptide (GLP-1) analog of human insulin. It stimulates the release of insulin from the pancreas only when glucose levels become too high. The drug class explores new territory between traditional metformin-based oral anti-diabetics and insulin-based medication, which is injected. The drug was also developed as an anti-obesity medication, for which it is in Phase III trials. Liraglutide was submitted both in Europe and the U.S. in 2008 as an anti-diabetic. While the FDA’s advisory committee has stated concerns with regard to cardiovascular safety profile. The European regulatory decision on Liraglutide is expected by mid-2009. Novo Nordisk (NVO) is the world’s leading producer of insulin and related diabetes medications. Market approval of its insulin analogue Liraglutide would further cement its position in the global insulin markets. 

(10) Multaq (Dronedarone) anti-arrhythmic from Sanofi-Aventis 

Multaq is an anti-arrhythmic agent, planned as a first-line therapy for the treatment of atrial fibrillation patients without severe heart failure. Atrial fibrillation remains the main cause for cardiovascular hospitalization, with about 7 million patients in Europe and the U.S. Multaq appears to be the only anti-arrhythmic drug that has shown a significant reduction of mortality in atrial fibrillation patients, and it has a favorable safety profile. Sanofi-Aventis filed Multaq with the European regulator EMEA in June 2008. In the U.S., the FDA advisory committee which was to announce a decision on Multaq on April 30, again delayed seeking more data on its cardiovascular safety. Sanofi now expects the approval in the second quarter. Sanofi-Aventis’ two main existing blockbuster drugs, Plavix and Lovenox, is threatened by generic competition over the next few years. Sanofi had to withdraw anti-obesity drug, Acomplia, from the market in 2007 because of safety concerns.