Many new and unique drugs are approved for marketing in the USA in 2012. The FDA approved a total of 39 new drugs, nine more than 2011 and the highest number since 1996, when 53 NMEs got approvals. New drug therapies were approved for cancer treatment, cystic fibrosis, basal cell carcinoma, myelofibrosis and management of HIV. New NMEs were approved for the treatment of multiple sclerosis, chronic weight management, overactive bladder, actinic keratosis, erectile dysfunction, glaucoma, respiratory distress syndrome, and COPD.
These approvals also include nine new drugs for orphan diseases, which affect fewer patients with rare conditions. The U.S. pharma companies continued to bring life-saving drugs to patients in 2012, often more quickly than anywhere else in the world. Most of the drugs were approved by the FDA for U.S. patients at a faster rate than other countries. This reflects in the growing efficiency of the drug review process. The short approval time is partly due to the changes imposed under the Prescription Drug User Fee Act (PDUFA), which aids the FDA in collecting fees for reviewing products to accelerate approval pathways for companies developing therapies for rate diseases. It is expected that most of those approved in 2012 would bring substantial improvements in healthcare of patients and contribute to the growth of the brand market.
There are several breakthrough drugs or milestones in 2012. The foremost first-in-class product of 2012 is ivacaftor (Kalydeco), a groundbreaking treatment for cystic fibrosis. Cystic fibrosis (CF) is a genetic disorder that affects the lungs, and also the pancreas, liver, and intestine. CF is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator, which regulates the movement of chloride and sodium ions across epithelial membranes in the lungs. CF is characterized by abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions, and results in frequent lung infections and ultimately leads to an early death.
New drugs of 2012 include nearly a dozen new agents to treat cancer. Vismodegib (Erivedge) is the first drug indicated for advanced basal cell carcinoma, a form of the most common skin cancer. Several agents are approved for metastatic forms of cancer including pertuzumab (Perjeta) for breast cancer, regorafenib (Stivarga) for colorectal cancer, enzalutamide (Xtandi) for prostate cancer, and ziv-aflibercept (Zaltrap) for colorectal cancer.
Two high-profile drugs from big pharma companies in 2012 include apixaban (Eliquis, BMS) for reducing stroke risk in patients with irregular beartbeats, and pasireotide (Signifor, Novartis AG) for Cushing’s disease, caused by hyperscretion of the adrenal hormone cortisol.
In the antibiotic/ vaccine segment, two new products (Menhibrix and Stribild) were approved for the treatment of infectious conditions. The list of antiepileptics has expanded with the addition of two new drugs, clobazam for seizures associated with Lennox-Gastaux syndrome, and perampanel (Fycompa) for the treatment of partial-onset seizures with or without secondarily generalized seizures. Despite the availability of over two dozen antiepileptic drugs, one-third of patients exhibit seizures that are intractable to current drug therapy.
Nine new drugs of 2012 (25 per cent) were new NMEs approved to treat rare or orphan diseases that affect 200,000 or fewer patients in the United States. This is significant because patients with rare diseases often have few or no drug treatment options. Examples of rare diseases that now have new effective treatment options include myelofibrosis (ruxolitinib), type-1 Gaucher disease (taliglucerase alfa), and Lennox-Gastaut syndrome (clobazam), a difficult-to-treat form of childhood-onset epilepsy.
The 2012 FDA approvals list includes a new erectile dysfunction drug (avanafil), a treatment for overactive bladder (mirabegron), a new drug for weight-loss, one agent used in a test to rule out Alzheimer’s disease (florbetapir F18), a new agent for reducing intraocular pressure in patients with glaucoma or ocular hypertension (tafluprost), and a drug for chronic management of bronchospasm in COPD, a disease of the lungs in which the airways narrow over time and this limits airflow to and from the lungs, causing shortness of breath (dyspnea). Linaclotide (Linzess) has been approved for irritable bowel syndrome with consitition (IBS), a intestinal condition characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits such as diarrhea or constipation.
The 2012 list also includes teriflunomide (Augagio), a new drug for relapsing forms of multiple sclerosis (MS), an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. MS takes several forms, with new symptoms occurring either in discrete attacks (relapsing forms) or accumulating over time (progressive forms).
In 2012, there were only four companies (Forest Labs, Roche-Genentech, Sanofi, and Pfizer) that got more than one drug approved out of the 39. Pfizer reived a total five of the 39 approvals, a record number for this industry leader.
Research innovation is once gain beginning to pay off. The introduction of 39 new drugs in 2012 underscores an efficient regulatory process. The list includes a total of 10 drugs for cancer treatment and 9 products with orphan drug status. The notable breakthroughs are ivacaftor (cystic fibrosis), vasmodegib (skin cancer), HPC-C (human cord blood product), ruxolitinib (myelofibrosis) and a new combination drug to treat HIV. Many unique agents were approved for the treatment of macular degeneration, chronic weight management, overactive bladder, actinic keratosis, erectile dysfunction, glaucoma, respiratory distress syndrome, and COPD.
Ruxolitinib (Jakafi) is the first drug to be approved for patients with myelofibrosis, a cancer that affects bone marrow. Myelofibrosis is a rare disease in which the bone marrow is replaced by scar tissue, forcing blood cells to be made in the liver or spleen rather than in the bone marrow. This causes enlarged spleens, pain, anemia, fatigue and other symptoms.
The PDUFA, which helps the FDA in collecting fees for reviewing NDAs and ANDAs, has certainly provided accelerated approval time. The average length of approval has decreased substantially since the advent of PDUFA in 1992 from 19 months in to 9.9 months in 2011.
The robust rate of new drug approvals in 2012 unveils unique and emerging trends in drug discovery especially in the field of rare diseases or orphan drug indications. Almost half (45 per cent) of NMEs approved in 2012 are the first in their class. Four out of five (81per cent) NMEs approved in 2012 were first approved in the U.S., suggesting that the U.S. continues to lead the world in first approval of new drug products. This is thought to benefit U.S. patients from early access to such innovative treatments. According to reports, the new drug research and development paradigm is shifting rapidly from traditional big pharma to venture capital backed small companies. The exciting news is that many such companies are successfully bringing innovative new products to market.
Overall, the year 2012 witnessed a record approval of 39 new drugs including several orphan drugs developed for treating rare diseases. However, there is bleak scope for reaping big revenue because most of these drugs are approved for narrow-spectrum indications with limited market potential. With the exception of a few agents, many new drugs are certainly not expected to become blockbusters. It reaffirms the new trends adopted by big drug makers staying away from super-hit blockbusters into more specific or personalized drugs to maintain a steady revenue in the current generics era. Nevertheless, the new drug approval list unveils unique and reemerging trends indicating that the pharma companies are poised for big growth from new brands approved for marketing.The business experts also forecasts a good year for drug makers in 2013.
(The author is Editor-in-Chief, International Journal of Pharmaceutical Sciences and Nanotechnology and Professor of Texas A&M University College of Medicine, Bryan, Texas, USA)