Horizon Lines: A Yearly Review of NDAs - 2015

• Tara Innovations LLC

For decades, the regulation and control of new drugs in the United States has been based on the New Drug Application (NDA). Since 1938, every new drug has been the subject of an approved NDA before U.S. commercialization. This column summarizes details on all the NDAs approved in the year 2015. A total of 154 NDAs were approved in 2015 which is ~15.8% more as compared to 2014.¹ The details on individual NDAs can be obtained from earlier columns.^2-6 NDAs 505 b(1) and 505 b(2) are considered in this summary. Figure 1 depicts NDAs approved for old (previously approved drug molecules) and new drug molecules. Old molecules in particular refer to NDA approvals for already approved molecules where certain changes such as an alteration of patient population, an approval of new indication etc. were completed.

 Figure 1. Month-wise comparison of approvals for old and new drug molecules in 2015

A month-wise distribution of all the NDA’s and its respective comparison with previous year provides a better insight in the trend for appr als.

Figure 2 shows the comparison of NDAs approved in 2014 and 2015 over the months. In the beginning of 2015, the number of NDA approvals was more compared to 2014. It is interesting to note that during the months of May and June, fewer NDAs were approved in both years. In the last quarter of the year, more NDAs were approved in both years.

 Figure 2. Comparison of NDAs approved month-to-month during 2015 and 2015

A dosage form can be a critical parameter for any product. Liquids as a category represents injections (intravenous, subcutaneous, intramuscular etc.), oral liquids (solutions, suspensions, emulsions etc.), electrolyte replacement solutions, ophthalmic, nasal or otic drops etc. Tablets and capsules contribute to a majority of solid dosage forms.

 Figure 3. Number of formulations approved in the year 2015 based on dosage forms.

Figure 3 shows the number of dosage forms approved in the year 2015. In the year 2015, the highest numbers of NDAs were approved for liquids. The next popular dosage forms were tablets and capsules. Some other dosage forms such as powder, topical gel, foam, intrauterine device, buccal films, granules, were approved in fewer numbers. An overall look at the trend for 2015 shows an increasing trend towards developing novel dosage forms like gels, foam or films in the future.

 Figure 4. Proportion of large versus small molecules in NDAs

In recent years, there has been an increased interest in large molecules owing to advanced research for diseases like cancer. For the purpose of this article, large molecules were defined as those with molecular weights over 1000 Daltons. Approximately 30% of total NDA’s approved in this year were large molecules while the remaining 70% were small molecules (Figure 4). A considerable number of large molecules (~30%) were monoclonal antibodies and other biomolecules, which were primarily used for treating cancers and hormonal disorders. The percent of NDAs approved for large molecules in 2014 were 39.9%, slightly higher than in 2015. The majority of large molecules are used to treat cancer, diabetes and blood related disease conditions.

It was observed that many big companies applied for a number of NDA’s and obtained approvals. Figure 5 represents the companies with three or more NDA approvals. It is interesting to note that big pharmaceutical companies like Pfizer and Genentech received only four and three NDA approvals, respectively. Novartis ranked top among all the pharmaceutical companies with ten approvals. Bristol-Myers Squibb and Boehringer Ingelheim Pharmaceuticals, Inc. ranked second with seven NDA approvals each. Some other big companies like Teva, Celgene Corporation, Regeneron Pharmaceuticals Inc., Allergen etc. received approvals for less than three NDAs.

 Figure 5. List of companies with 3 or more NDA approval in 2015

Another important scenario to review is the number of NDAs reported for different disease condition. Figure 6 depicts a bar-chart listing the number of NDAs approved for various medical conditions. The majority of NDAs were approved for various cancers (lymphoma, leukemia, melanoma, lung cancer, neuroblastoma, breast cancer, thyroid cancer etc.), which was about 20% of total NDAs approved in the year. Management of schizophrenia, seizures, Parkinson's, epilepsy, depression, opiate dependence and overdose, multiple sclerosis and some CNS stimulants were classified as CNS disorders. Approximately 15% of the total NDAs were for the management of CNS disorder. A considerable amount of NDAs was approved for other major disease conditions like blood related disorders, cardiac disorders and infectious diseases. Blood related disorders include anemia, hemostasis, thromboembolism, deep vein thrombosis, chronic iron overload, hemophilia etc. Ischemic stroke prophylaxis, management of chronic heart failure, high cholesterol, hypertension, acute coronary syndrome etc., were classified as cardiac disorders. Infectious diseases include viral, bacterial and fungal infections.

 Figure 6. List of NDAs approved for various medical conditions in 2015

Cancer, blood-related disorders, CNS disorders, infectious diseases and cardiac disorders were the top five diseases for which NDA approvals were received.

There were few NDAs, which were approved for the first time for a particular disease. Drug molecules for novel medical conditions for which NDA approval were received for the very first time are listed in Table 1.

Table 1. Some unique NDAs approved in 2015

Conclusion

This review summarizes various trends observed for approved NDAs in 2015. It will be important to conduct such an analysis every year to understand year-to-year trends. Liquid products were the most popular dosage form in 2015. The key trend was – a remarkable interest in large molecules as monoclonal antibodies for cancer and blood related disorder. It is interesting to note that some new companies are in the list to obtain more than three NDAs approved. Products for cancer, cardiac disorder and blood related disorder contributed major numbers in NDAs approval.

References

1. Horizon Lines: A Yearly Review of NDAs – 2014, Harshada Sant, Rucha Kelkar and Hemant Joshi, Pharmaceutical Outsourcing, July-August, Volume 16, Issue 4, 2015, www.pharmoutsourcing.com.
2. A review of NDAs : January – February, 2015, Harshada Sant and Hemant Joshi, Pharmaceutical Outsourcing, September-October, Volume 16, Issue 5, 2015, www.pharmoutsourcing.com.
3. Horizon Lines: A Review of NDAs – March – April, 2015, Sonal Pathak, Harshada Sant and Hemant Joshi, Pharmaceutical Outsourcing, November-December, Volume 16, Issue 7, 2015, www.pharmoutsourcing.com.
4. Horizon Lines: A Quarterly Review of NDAs – May - July, 2015, Sonal Pathak, Harshada Sant and Hemant Joshi, Pharmaceutical Outsourcing, January-February issue, Volume 17, Issue 1 2016, www.pharmoutsourcing.com.
5. Horizon Lines: A Quarterly Review of NDAs – 3Q15, 2015, Sonal Pathak, Harshada Sant and Hemant Joshi, Pharmaceutical Outsourcing, March-April, Volume 17, Issue 2, 2016, www.pharmoutsourcing.com.
6. Horizon Lines: A Quarterly Review of NDAs – 4Q15, 2015, Sonal Pathak, Harshada Sant and Hemant Joshi, Pharmaceutical Outsourcing, May-June, Volume 17, Issue 3, 2016, www.pharmoutsourcing.com
7. Food and Drug Administration, www.fda.gov.