Trends in new NMEs,
biologics In 2011, the US FDA approved many unique and new drugs for COPD, DVT
SLE, and epilepsy. In addition, several new biologicals were approved in the
past year for treatment of macular degeneration, acute lymphoblastic leukemia,
Hodgkin lymphoma, melanoma, chronic hepatitis C, and SLE. Category-wise
analysis indicate that eleven of the 30 NMEs were new drugs approved for orphan
diseases, while twelve are considered first-in-class drugs. It is expected that
these new drugs would bring substantial improvements in healthcare of many
patients. The US FDA has approved over 30 new drugs for marketing in the United States.
This list includes novel new drugs, known as NMEs, biologics and new
indications for drugs already approved.
Tracks for expediting new drug review and approval The US FDA has various tracks for expediting new drug review and approval
for marketing, including priority review, fast track and accelerated approval.
Twelve of the 30 NMEs approved in 2011 are considered first-in-class, referring
to drugs which use a new a unique mechanism of action for treatment of the
health condition (CDER, 2012). Fast track status is considered if the product
is intended for treatment of a serious or life-threatening condition and
addresses an unmet medical need. There are several high-impact milestones
in 2011. The foremost first-in-class product of 2011 is belimumab (Benlysta),
the first new drug approved to treat SLE in over 50 years. SLE is a serious and
potentially fatal autoimmune disease that attacks healthy tissues, including
the joints, skin, kidneys, lungs, heart, and brain. SLE flare-ups are treated
with NSAIDs, corticosteroids, immunosuppressants, and antimalarials. These
agents are not very effective in many patients. It is hoped that belimumab may offer
a better alternative for the treatment of SLE. Another noteworthy new drug is
brentuximab vedotin (Adcetris), the first new drug to treat Hodgkin Lymphoma in
over 30 years. Lingagliptin (Tradjenta), an antidiabetic agent, is another
major drug approved in 2011. It belongs to the gliptin class that affects
endogenous incretin hormones involved in regulation of glucose homeostasis.
Like sitagliptin, lingagliptin is a potent inhibitor of dipeptidyl peptidase-4
enzyme, which inactivates the incretins.New drugs of 2011 include two new
treatments for hepatitis C (telaprevir and boceprevir). Several anticancer
drugs were introduced in 2011 including crizotinib, brentuximab, abiratirone,
and vandetanib. Two new drugs--roflumilast (Daliresp) and
indacaterol (Arcapta Neohaler)--have been approved for COPD characterized by
the occurrence of chronic bronchitis or emphysema that leads to dyspnea. In the antibiotics field, fidaxomicin (Dificid) has been approved for the
treatment of Clostridium difficile-associated diarrhea. Ablifercept (Eylea) is
another important new drug of 2011 approved for preventing vision loss from
macular degeneration. Ticagrelor (Brilinta) is a cardiovascular agent approved
for preventing heart attack. Belatacept (Nulojix) is a new treatment to prevent
kidney transplant rejection. Vilazodone hydrochloride (Viibryd), a SSRI type
antidepressant similar to those of citalopram, escitalopram, fluvoxamine,
paroxetine, and sertraline, was approved in 2011 for major depressive disorder
(Hussar, 2011). Two high-profile drugs from big pharma companies in 2011
include ipilimumab (Yervoy, BMS) for melanoma and ticagrelor (Brilinta,
AstraZeneca) for cardiovascular conditions. In 2011, two new antiepileptics
(ezogabine and clobazam) were approved for the treatment of epilepsy, a common
neurological disorder characterized by the repeated occurrence of seizures. The
list of antiepileptics has expanded with the addition of these two new drugs.
Despite the availability of over two dozen antiepileptics, many patients (up to
30%) exhibit seizures that are intractable to current drug therapy.For patients
with acute lymphoblastic leukemia (ALL), who have developed an allergy
(hypersensitivity) to E. coli derived asparaginase and pegapargase chemotherapy
drugs used to treat acute lymphoblastic leukemia. Intrvitreal injection It is
an enzyme that catalyzes the hydrolysis of asparagine to aspartic acid and thus
deprives the leukemic cell of circulating asparagine. Leukemic cells are unable
to synthesize asparagine.Certain patients with late-stage (locally advanced or
metastatic), non-small cell lung cancers who express the abnormal anaplastic
lymphoma kinase gene.
Conclusion New drug development and approval has
several hurdles. The main hurdle is to demonstrate superior
therapeutic efficacy of the new drug without undue adverse effects that affects
the patient’s quality of life. Novel drug approval appears to remain
steady or decline during the past decade (Figure 1). In the 10-year period
between 2002 and 2011, the FDA approved 235 NMEs including one-third
first-in-class drugs (Swinney and Anthony, 2011; CDER, 2012). Thirty NMEs were
approved in 2011, representing the second highest total in the past ten years.
In 2004, there were 36 NMEs approved, the highest in the past ten years.
Analysis of the trends during the past 10 years suggests an average 24 NME
approvals per year. However, the overall number of NMEs approved over the past
10 years has not been encouraging, with declining trends. While harsh economic
econditions continue to force large parmaceutical companies and biotech firms
to focus on the bottom line and scale back R&D budgets, the new drugs of
2011 would certainly represent a turnaround to some companies pursuing
high-risk, high-reward drug development programs. Research innovation is once
gain beginning to pay off. Introduction of 30 NMEs in 2001 underscores a robust
success rate relative to the past seven years. The drug approvals in 2011
reveal a unique new trend in drug discovery in the face of stiff competition
from generic products and declining revenues. In the existing climate of
reduced pipeline for NMEs, the future and survival of big companies rests
heavily on their unique niche products and biologics with relatively less
competition from generic manufacturers. Drug repositioning or new indication
(e.g. gabapentin for restless legs syndrome) is a strategy focusing on new
indications not necessarily related to the original disease focus. However, the
competition for biosimilars is growing by the hour and therefore, crafting
innovative generic biologicals is vital for generic biotech companies.
Nevertheless, the new drug approval list unveils unique and emerging trends in
drug discovery especially in the current generics era.There is huge decline in
pharmaceutical R&D efficiency (Scannell et al., 2012). Despite the large
investments made in drug discovery in the past decade, there is still a dearth
of new blockbuster drugs with annual sales of over $1 billion. This highlights
the persistence of a model of drug development that has not adapted to changes
in science or the marketplace. The phenotype screening model is escalating in
cost due to lack of mechanistic rationale. The strategy of merger, pursued by
many companies to compensate for the failure to develop new drugs, has
compounded the problem on an already inefficient process. This reduced effort
reflects rather a change in business model. The productivity decline is scary
and reversing it will be important to the big pharma’s survival (Scannel et al.,
2012). However, there are unique trends that are emerging to drive the current
new drug discovery. The two issues impacting on the revenue from innovative
brands include patent cliff and generics pressure. There are new opportunities
to address the current challenges in this field. Major obstacles can be
successfully overcome by adapting a “mechanism-based” (target-based) drug
discovery that may reduce costs and accelerate drug development (Reddy and
Woodward, 2004). Selection of a reliable target is vital for the success of
this strategy (Mullard, 2011). In the United States, academic institutes
and the NIH have been scaling up early drug discovery efforts. Armed with new
ideas, targets and magnificent capabilities, they are now able to take projects
much beyond target identification and optimize compounds that “chemically
validate” a target and thereby jump-start the process of translational
research. As new partnerships between academia and industry are established,
institutes armed with high-throughput translational research are well-placed to
play a central role in the newly emerging model for drug discovery and
biomarker research. (The author is Editor-in-Chief, International Journal of
Pharmaceutical Sciences and Nanotechnology, and associate prof, Dept of
Neuroscience and Experimental Therapeutics, Texas
A&M University
System Health
Science Center,
College of Medicine,
Bryan, Texas,
USA)
