The Class of 2016: New Molecular Entities

The US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) has approved 16 new molecular entities (NMEs) thus far in 2016, off from the pace in 2015 and 2014 when 22 NMEs had been approved through the end of August 2015 and 26 NMEs had been approved through August 2014. So which drugs have made the cut thus far?

Although NME approvals do not follow a chronological path, the number of NME approvals are down thus far in 2016, following two strong years of NME approvals in 2015 and 2014 when 45 and 41 NMEs were respectively approved for those full calendar years. DCAT Value Chain Insights takes an inside look.

Trends in NME approvals
Last year was a banner year for approval of NMEs with 45 NMEs approved by FDA’s CDER. Of the 45 NMEs approved, 32 were small molecules (new drug applications (NDAs)), one was an insulin analogue approved as a NDA, and 12 were biologics (biologics license applications (BLAs). So how did the 45 NMEs approved in 2015 compare with previous years?

The FDA’s CDER approved 41 NMEs in 2014, 30 NDAs (i.e., small molecules) and 11 BLAs (i.e., biologics), an uptick from 2013 and  on par with 2012. FDA’s CDER approved 27 NMEs in 2013 and 39 NMEs in 2012. From 2005 to 2013, CDER averaged 25 NME approvals per year, which was bolstered by approval levels in 2004 (36 NMEs approved), 2011 (30 NMEs approved), 2012 (39 NMEs approved), and 2013 (27 NMEs approved). The period of 2005 to 2010 was a slower period for NME approvals. In 2005, 20 NMEs were approved, 22 in 2006, 18 in 2007, 24 in 2008, 26 in 2009, and 21 in 2010. Table I summarizes NME approvals for small molecules and biologic over the past five years (2010 to 2015).

Table I: Small Molecule and Biologics New Molecular Entities Approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research, 2010 to 2015.
Year Number of New Molecular Entities (NMEs) Approved Number of NME NDAs approved (small molecules) and NME BLAs approved (biologics)
2010 21 NMEs approved 15 NDAs (small molecules) and 6 BLAs (biologics)
2011 30 NMEs approved 24 NDAs (small molecules) and 6 BLAs (biologics)
2012 39 NMEs approved 33 NDAs (small molecules) and 6 BLAs (biologics)
2013 27 NMEs approved 24 NDAs (small molecules) and 3 BLAs (biologics)
2014 41 NMEs approved 30 NDAs (small molecules) and 11 BLAs (biologics)
2015     45 NMEs approved 33 NDAs (32 small molecules and one insulin analog*), 12 BLAs (biologics)
Note: Novo Nordisk’s Tresiba (insulin degludec injection) is a long-acting basal human insulin analog produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification. It was approved as a new drug application not as a biologics license application. Source: US Food and Drug Administration’s Center for Drug Evaluation and Research


The NME Class of 2016 thus far
So what are the NMEs approved thus far in 2016? As of the end of August 2016, the FDA’s CDER had approved 16 NMEs, which included 12 NDAs (which included two diagnostic imaging agents) and five biologics (see Table I at the end of the article).

Four of the five biologics approvals are from the large pharmaceutical companies. Biogen received FDA approval for its multiple sclerosis drug, Zinbryta (daclizumab). Eli Lilly and Company received FDA approval for Taltz (ixekizumab) for treating adults with moderate-to-severe plaque psoriasis. Roche gained approved for its immuno-oncology drug, Tecentriq (atezolizumab), for treating advanced bladder cancer, and Teva Pharmaceuticals gained the nod for Cinqair (reslizumab) for treating severe asthma. The final biologic, Elusys Therapeutics’ Anthim (obiltoxaximab), is a niche drug for treating inhalational anthrax in combination with appropriate antibacterial drugs.

On the small-molecule side, key drug approvals by the large pharmaceutical companies include AbbVie’s and Roche’s Venclexta (venetoclax) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have a chromosomal abnormality called 17p deletion and who have been treated with at least one prior therapy. Venclexta is the first FDA-approved treatment that targets the B-cell lymphoma 2 (BCL-2) protein, which supports cancer cell growth and is overexpressed in many patients with CLL. Venclexta is indicated for daily use after detection of 17p deletion is confirmed through the use of the FDA-approved companion diagnostic, the Vysis CLL FISH probe kit. Venclexta is manufactured by AbbVie and marketed by AbbVie and Roche’s Genentech with the drug jointly commercialized by AbbVie and Genentech in the US and commercialized by AbbVie outside of the US. The Vysis CLL FISH probe kit is manufactured by Abbott Molecular.

Two new drugs to treat hepatitis C virus (HCV) infection are combination therapies, Gilead Sciences’ Epclusa (sofosbuvir and velpatasvir) and Merck & Co.’s Zepatier (elbasvir and grazoprevir). Epclusa (sofosbuvir 400 mg/velpatasvir 100 mg) is an all-oral, pan-genotypic, single tablet regimen for the treatment of adults with genotype 1-6 chronic (HCV) infection. It is a combination therapy using one of the company’s key active ingredients, sofosbuvir, the active ingredient in the company’s HCV treatment, Sovaldi, which posted 2015 sales of $5.3 billion. Gilead’s combination HCV therapy, Harvoni (ledipasvir and sofosbuvir), posted 2015 sales of $13.9 billion. Merck & Co. also received approval for Zepatier (elbasvir and grazoprevir) for treating chronic HCV genotypes 1 and 4 infections in adult patients.

Sanofi received FDA approval for Adlyxin (lixisenatide) to improve glycemic control (blood sugar levels) in adults with Type 2 diabetes. Diabetes is an important product franchise for Sanofi, accounting for 2015 revenues of EUR 7.58 billion ($8.48 billion). New diabetes drugs is an important part of Sanofi’s product strategy in diabetes as it faces generic competition for Lantus (insulin glargine), its top-selling product in 2015 with sales of EUR 6.39 billion ($7.22 billion).

Shire received approval for Xiidra (lifitegrast ophthalmic solution) to treat dry-eye disease. Xiidra is the first medication in a new class of drugs, called lymphocyte function-associated antigen 1 (LFA-1) antagonists, approved by the FDA for dry-eye disease.

Table II: 2016 New Molecular Entities (New Drug Applications (NDAs) and Original Biologics License Applications (BLAs) Approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research as of August 2016.
Company Property name (active ingredient); application type Indication
AbbVie and Roche* Venclexta (venetoclax); NDA Chronic lymphocytic leukemia in patients with a specific chromosomal abnormality
Acadia Pharmaceuticals Nuplazid (pimavanserin); NDA Hallucinations and delusions associated with psychosis experienced by some people with Parkinson’s disease
Advanced Accelerator Applications Netspot (gallium Ga 68 dotatate injection); NDA A diagnostic imaging agent to detect rare neuroendocrine tumors
Blue Earth Axumin (fluciclovine F 18); NDA Diagnostic imaging agent to detect recurrent prostate cancer
Biogen Zinbryta (daclizumab); BLA Multiple sclerosis
Eli Lilly and Company Taltz (ixekizumab); BLA Adults with moderate-to-severe plaque psoriasis
Elusys Therapeutics Anthim (obiltoxaximab); BLA Inhalational anthrax in combination with appropriate antibacterial drugs
Gilead Sciences Epclusa (sofosbuvir and velpatasvir); NDA All six major forms of hepatitis C virus
Intercept Pharmaceuticals Ocaliva (obeticholic acid); NDA Rare, chronic liver disease
Jazz Pharmaceuticals** Defitelio (defibrotide sodium); NDA Adults and children who develop hepatic veno-occlusive disease with additional kidney or lung abnormalities after they receive a stem-cell transplant from blood or bone marrow called hematopoietic stem cell transplantation
Merck & Co. Zepatier (elbasvir and grazoprevir); NDA Chronic hepatitis C virus genotypes 1 and 4 infections in adult patients.
Roche Tecentriq (atezolizumab) BLA Urothelial carcinoma, the most common type of bladder cancer
Sanofi Adlyxin (lixisenatide); NDA Improve glycemic control (blood sugar levels) in adults with Type 2 diabetes
Shire Xiidra (lifitegrast ophthalmic solution); NDA Dry eye disease
Teva Pharmaceuticals Cinqair (reslizumab); BLA Severe asthma
UCB Briviact (brivaracetam); NDA Partial onset seizures in patients age 16 years and older with epilepsy

* Venclexta (venetoclax) is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the US and commercialized by AbbVie outside of the US. **Jazz Pharmaceuticals acquired Gentium in 2014 and with it, Defitelio (defibrotide sodium) 

Source: US Food and Drug Administration’s Center for Drug Evaluation and Research and company information.


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