Pipeline Filled with Promising Drugs

Cincinnati—Despite patents for blockbuster drugs such as Lipitor^® (atorvastatin calcium) and Plavix^® (clopidogrel bisulfate) expiring in the past year, pharmaceutical manufacturers have received some positive news in 2012 when it comes to drug approvals.

Through September, the FDA approved 24 drugs this year, a larger number in the first 9 months than in any of the previous 5 years. The total included 14 specialty and 10 traditional products, a shift from a few years ago when traditional drugs dominated.

“It has been a good year so far,” said Brian W. Kolling, PharmD, senior director of pipeline and trend forecasting for Medicare Part D at OptumRx.

The primary growth area is oncology, with the agency approving 8 new molecular entities for cancer this year. By 2017, annual oncology drug sales could exceed $100 billion, according to Dr. Kolling, who discussed the latest trends in pharmaceuticals during a Contemporary Issues session at the AMCP meeting.

New mechanisms may offer hope for approvals, as well. Dr. Kolling mentioned the following mechanisms as encouraging for manufacturers: sodium glucose cotransporter-2 (SGLT-2) inhibitors for diabetes; proprotein convertase subtilisin/kexin type 9 for cholesterol; janus kinase (JAK) inhibitors for autoimmune diseases such as rheumatoid arthritis and inflammatory diseases; and cathepsin K inhibitors for osteoporosis.

Still, Dr. Kolling said the industry faces some challenges. Generic drugs are becoming more popular, accounting for more than 80% of the United States market. The success rate of drugs getting approved is flat or declining, according to Dr. Kolling.

He added that drug development cycle rates are increasing, too. From preclinical studies to approval typically takes 10 to 13 years.

“There is more pressure on products to get through,” Dr. Kolling said. “But there are also more products [in development].”

In addition to oncology, infectious diseases, rheumatology, and diabetes are other areas that are growing, according to Dr. Kolling. Meanwhile, the pipelines for cardiology and central nervous system drugs are slowing.

Here is an overview of the drug classes that Dr. Kolling mentioned during his presentation.

Cardiovascular

Dr. Kolling included the following areas in this category: cholesterol, hypertension/congestive heart failure, anticoagulants/antiplatelets, and arrhythima. The market size is expected to decrease from $77 billion in 2010 to $65 billion in 2016, partially because of the patent expiration of atorvastatin, the top selling drug in history, which generated approximately $8 billion in sales for its manufacturer, Pfizer Inc.

Apixiban, an oral anticoagulant intended to prevent strokes in patients with atrial fibrillation, is among the 3 most promising drugs in the pipeline regardless of disease state, according to Dr. Kolling. The drug is a factor Xa inhibitor manufactured by Pfizer Inc. and Bristol-Myers Squibb.

The FDA extended its review by 3 months in February and then sent a complete response letter to the manufacturers asking for more information on apixiban’s efficacy in preventing stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the agency did not request further trials. The new Prescription Drug User Fee Act date for apixiban is March 17, 2013.

Dr. Kolling said anticoagulants/antiplatelets are the top growing area among cardiovascular categories. For cholesterol drugs, branded statins remain dominant despite the presence of generics, according to Dr. Kolling. He added that hypertension is a mature market, and there are not many drugs in the pipeline intended to treat hypertension.

Diabetes

Patients with diabetes will likely have more options in the coming years. In 2010, the diabetes market size was $24.6 billion, with insulins accounting for >63% of sales. By 2016, insulins will account for approximately 46% of the $37.9 billion diabetes market as new classes of drugs such as glucagon-like peptide-1 (GLP-1) receptor analogues, dipeptidyl peptidase-IV (DPP-IV) inhibitors, and SGLT-2 inhibitors become more prevalent.

Insulin degludec, a long-acting basal insulin from Novo Nordisk, is expected to gain FDA approval by the end of the year, according to Dr. Kolling. In a phase 3 trial, patients who took insulin degludec had a lower fasting glucose level and a trend toward lower nocturnal hypoglycemia compared with a group that received insulin glargine. Eli Lilly and Company is also developing a basal insulin, which it hopes will compete with insulin degludec and insulin glargine, although phase 3 results are not expected until 2014.

In April, the FDA rejected the approval of alogliptin (a DPP-IV inhibitor) and requested cardiovascular data. Takeda Pharmaceutical Company Limited, the manufacturer, resubmitted its application for alogliptin and expects to hear back about the approval by early 2013. The company also filed for a combination of alogliptin and pioglitazone and alogliptin plus metformin.

Dr. Kolling said the following SGLT-2 inhibitors could gain approval: dapagliflozin (which the FDA rejected in June), canagliflozin, and empagliflozin. In addition, lixisenatide, albiglutide, and dulaglutide are GLP-1 analogues that could be approved in the next year or two. By 2015, Dr. Kolling said there could be 6 FDA-approved GLP-1 analogues.

Central Nervous System

The central nervous system market is expected to decline from $41.5 billion in 2010 to $26.4 billion in 2016, according to Dr. Kolling. Most antidepressants prescribed are generics, and a few major antipsychotics have lost patent protection recently, including Zyprexa^® (olanzapine) and Seroquel^® (quetiapine).

Central nervous system drugs that could be approved in the coming months include levomilnacipran (for depression), cariprazine (for schizophrenia and bipolar mania), loxapine (for schizophrenia and bipolar mania), and suvorexant (for primary insomnia).

The category will also be affected by the December 2013 generic launch for Cymbalta^® (duloxetine), an antidepressant.

Respiratory

In the respiratory category, Dr. Kolling said there is a trend toward the combination of an inhaled corticosteroid and a long-acting beta agonist to treat asthma as well as the combination of a long-acting muscarinic antagonist and a long-acting beta agonist to treat chronic obstructive pulmonary disease (COPD).

In May 2013, the FDA is expected to make an approval decision on the combination of fluticasone and vilanterol for COPD. Dr. Kolling said phase 3 data indicated mixed results when measuring exacerbations and forced expiratory volume. In addition, some people taking the highest dose of the drug experienced fatal pneumonia.

Other products for COPD that Dr. Kolling indicated may be approved between 2012 and 2015 include the combination of vilanterol and umeclinidium; the combination of indacaterol and glycopyrronium; and the combination of olodaterol and tiotropium.

Pain/Inflammation

Since losing patent protection for atorvastatin, Pfizer Inc. has lost billions of dollars in sales. Tofacitinib, an oral JAK1 and JAK3 inhibitor to treat rheumatoid arthritis, may help the company regain some of that revenue, according to Dr. Kolling. The FDA is expected to rule on the approval for tofacitinib by the end of the year.

In phase 3 trials, patients taking tofacitinib had better efficacy compared with those taking tumor necrosis factor inhibitors, although they also had worse side effects. Dr. Kolling said patients taking tofacitinib may have to have renal, hepatic, and cardiovascular side effects monitored.

Pfizer Inc. is developing 2 other drugs in this category: a twice-daily formulation of oxycodone to treat chronic pain and oxycodone surrounding a naltrexone core.

Dr. Kolling mentioned Zogenix, Inc. has manufactured extended-release hydrocodone to treat moderate to severe chronic pain that has drug delivery technology similar to morphine sulfate and dexmethylphenidate hydrochloride, both of which are FDA-approved. The FDA is expected to rule on the approval for extended-release hydrocodone by March 2013.