Mid-Year Review: New Drug Approvals Stay on Track

By Patricia Van Arnum - DCAT Editorial Director

July 11, 2018

As we reach the mid-point of 2018, how are approvals of new molecular entities faring? As of the end of June, the FDA had approved 20 NMEs, a similar number as approved this time last year when the FDA had approved 23 NMEs by mid-year with an eventual total of 46 NMEs approved for 2017. Although the numbers are on par, how about the drugs themselves?

Small molecules are dominating thus far, with 15 small-molecule NME approvals and five biologic-based NME approvals. Only one third (35%) of the approvals are from the pharmaceutical majors with small to mid-sized companies showing the NME muscle thus far. DCAT Value Chain Insights takes an inside look.

Inside NME approvals thus far in 2018

As of June 30, 2018, The Center for Drug Evaluation and Research (CDER) of the US Food and Drug Administration (FDA) had approved 20 new molecular entities (NMEs), which is a similar pace set in 2017 when the FDA had approved 23 NMEs at the mid-point with an eventual total of 46 NME approvals in 2017. Although NME approvals do not necessarily follow a chronological track, the 20 NME approvals thus far set 2018 as a potential productive year for NME approvals.

The 46 NME approvals in 2017 was the second highest number of NME approved by FDA’s CDER, second only to the 53 NMEs approved in 1996. The uptick in NME approvals in 2017 resumes an upward trajectory beginning in 2011 (with the exception of 2013 and 2016) for NME approvals with 30 NMEs approved in 2011 and 39 in 2012. The exceptions were in 2013, which had a decline to 27 NMEs, and 2016, which had 22 NME approvals, but levels jumped again to 41 NMEs approved in 2014 and in 2015 when 45 NMEs were approved.

Table I at the end of the article enumerates the NME approvals thus far in 2018. Of the 20 NMEs approved thus far, small molecules are dominating thus far, with 15 small-molecule NME approvals and five-biologic-based NME approvals. Amgen’s Aimovig (erenumab-aooe), a drug to prevent migraine in adults, BioMarin Pharmaceutical’s Palynziq (pegvaliase-pqpz), a drug to treat phenylketonuria, an inherited disorder that increases the levels of phenylalanine in the blood, Merck & Co.’s and Sun Pharmaceutical's Ilumya (tildrakizumab) for treating moderate-to-severe plaque psoriasis, TaiMed Biologics USA’s Trogarzo (ibalizumab-uiyk) for treating HIV, and Ultragenyx Pharmaceutical’s Crysvita (burosumab-twza) for treating a rare, inherited form of rickets are the five biologics thus far approved in 2018 (see Table I at end of article). The five biologic-NME approvals thus far represent 25% of 2018 NME approvals thus far, which is slightly lower than previous full-year totals. In looking at the 46 NME approvals by FDA’s CDER, 34 or 74% were small molecules and 12 or 26% were biologics. The nearly quarter of NME approvals that were biologics were slightly down from the recent product mix for NME approvals. In 2016, 32% of the NME approvals were biologics, and in 2015 and 2014, 27% of NME approvals were biologics (see Table II at end of article).

Big Pharma and NME approvals

Of the 20 NME approvals thus far in 2018, seven or 35% were from the pharmaceutical majors (see Table I at end of article). Novartis, through its acquisition of Advanced Accelerator Applications in January 2018, added to its oncology portfolio with Lutathera (lutetium Lu 177 dotatate), a drug to treat gastroenteropancreatic neuroendocrine tumors, a type of cancer that affects the pancreas or gastrointestinal tract. As previously noted, Amgen received approval for Aimovig (erenumab-aooe), a drug to prevent migraines in adults, and Merck & Co. and Sun Pharmaceutical received approval for Ilumya (tildrakizumab) for treating moderate-to-severe plaque psoriasis. AstraZeneca gained FDA approval for Lokelma (sodium zirconium cyclosilicate, a drug to treat hyperkalemia (high potassium levels), and Eli Lilly and Company received approval for Olumiant (baricitinib) for treating moderately to severely active rheumatoid arthritis. Gilead Sciences gained an FDA nod with approval with a combination antiviral drug, Biktarvy (bictegravir, embitcitabine, and tenofovir alafenamide) for treating infection in adults who have no antiretroviral treatment history or to replace the current antiretroviral regimen. Johnson & Johnson’s Janssen Pharmaceutical received FDA approval for Erleada (apalutamid) for treating non-metastatic, castration-resistant prostate cancer.

Tracking blockbuster potential from 2018 NME approvals

Of the 20 NME approvals thus far, four have been slated by some analysts with blockbuster potential. A recent analysis by Clarivate Analytics, Drugs to Watch 2018 highlights 12 potential blockbusters entering the market in 2018. Of that list, four are NME approved this far. Gilead Sciences’ Biktarvy (tenofovir alafenamide + emtricitabine + bictegravir), Johnson & Johnson’s Erleada (apalutamide), Amgen’s and Novartis’ Aimovig (erenumab), and GW Pharmaceuticals’ Epidiolex (plant-derived cannabidiol).

Gilead Sciences’ Biktarvy (tenofovir alafenamide + emtricitabine + bictegravir) is a new single-tablet HIV treatment, which was approved by the FDA in February 2018. This once-daily tablet contains the new integrase inhibitor, bictegravir, plus the nucleoside reverse transcriptase inhibitor, tenofovir alafenamide and the nucleoside reverse transcriptase inhibitor, emtricitabine. A marketing-authorization application in the European Union was filed in July 2017.

Sales of $896 million are expected for Biktarvy in 2018, rising to blockbuster sales of $2.282 billion in 2019 and forecast to be $3.716 billion in 2022, according to the Clarivate report. The launch is expected to help Gilead gain market share from GlaxoSmithKline’s (GSK) HIV regimens based on the once-daily integrase inhibitor, Tivicay (dolutegravir), which includes GSK’s Triumeq (dolutegravir /lamivudine/ abacavir), which was launched in 2014.

Johnson & Johnson’s Erleada (apalutamide), which was approved by the FDA in February 2018, is the first FDA-approved treatment for nonmetastatic castration-resistant prostate cancer (CRPC). The CRPC market is dominated by oral next-generation anti-androgens, Johnson & Johnson’s Zytiga (iabraterone) and Pfizer’s and Astellas’ Xtandi (enzalutamide), which are both approved for CRPC that has metastasized. Clarivate projects blockbuster sales of Erleada in 2020 with sales of $1.200 billion. Sales are forecast to reach a $2.000 billion by 2022.

Amgen’s and Novartis’ Aimovig (erenumab), a drug to treat migraines, is expected to reach blockbuster status in 2022 with sales of $1.170 billion, according to Clarivate’s Drugs to Watch for 2018 report. It is one of several calcitonin gene-related peptide (CGRP) receptor inhibitors expected to enter the market over the next several years and has the potential to be the first-to-market CGRP inhibitor to market. CGRP, a neuropeptide, has been shown to be released during migraine attacks and may play a causative role in induction of migraine attacks, according to the report.

In August 2015, Amgen entered into a global collaboration with Novartis to jointly develop and commercialize treatments in the fields of migraine and Alzheimer's disease.The collaboration focuses on investigational Amgen drugs in the migraine field, including Aimovig. In April 2017, the collaboration was expanded to include co-commercialization of Aimovig in the US. For the migraine program, Amgen retains exclusive rights in Japan, and Novartis has exclusive rights in Europe, Canada, and the rest of the world.

Both Eli Lilly’s galcanezumab (once-monthly dosing) and Teva’s fremanezumab (once-monthly or quarterly dosing) filed for US approval in October 2017. Alder’s intravenously administered monoclonal antibody, eptinezumab (quarterly dosing), is in Phase III development, and a regulatory filing is expected to be filed in 2018. Aimovig is anticipated to become the market leader in the CGRP class, with forecasts of $1.170 billion in 2022, followed by Teva’s fremanezumab at $999 million (which has preferable quarterly dosing), according to the Clarivate report. Sales for galcanezumab in 2022 are forecast at $546 million and eptinezumab at $368 million with the eptinezumab forecast expected to increase to $946 million in 2023. Other oral CGRP inhibitors of note include Allergan’s atogepant and Biohaven’s rimegepant, according to the report.

Epidiolex (plant-derived cannabidiol) by GW Pharmaceuticals, a Cambridge, UK-based pharmaceutical company, is slated for blockbuster status for treating two forms of epilepsy: Lennox-Gastaut syndrome, a form of severe epilepsy that is characterized by multiple types of seizures and intellectual disability, and Dravet syndrome, another severe form of epilepsy. Following a new drug application submission to the FDA in June 2017, GW Pharmaceuticals’ Epidiolex (plant-derived cannabidiol) has the potential to become the first cannabinoid-based anti-epileptic medication. The FDA has granted the drug priority review with a PDUFA review date in June 2018. A marketing-authorization application for the drug in the EU was also submitted in December 2017. Clarivate projects 2022 sales at $1.191 billion.

Table I: Approvals of New Molecular Entities, New Drug Applications (NDAs) and Original Biologics License Applications (BLAs) by the US Food and Drug Administration’s Center for Drug Evaluation and Research as of June 30, 2018.
Company Brand name (active ingredient); application type Indication
Advanced Accelerator Applications (Novartis company) Lutathera (lutetium Lu 177 dotatate); NDA Gastroenteropancreatic neuroendocrine tumors, a type of cancer that affects the pancreas or gastrointestinal tract
Achaogen Zemdri (plazomicin); NDA Adults with complicated urinary tract infections
AkaRx Doptelet (avatrombopag); NDA Low blood platelet count (thrombocytopenia) in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure
Amgen Aimovig (erenumab-aooe); BLA Preventive treatment of migraine in adults
Array BioPharma Braftovi (encorafenib); NDA Unresectable or metastatic melanoma
Array BioPharma Mektovi (binimetinib); NDA Unresectable or metastatic melanoma
AstraZeneca Lokelma (sodium zirconium cyclosilicate); NDA Hyperkalemia (high potassium levels)
BioMarin Pharmaceutical Palynziq (pegvaliase-pqpz); BLA Phenylketonuria (inherited disorder that increases the levels of phenylalanine in the blood)
Eli Lilly and Company Olumiant (baricitinib); NDA Moderately to severely active rheumatoid arthritis
Gilead Sciences Biktarvy (bictegravir, embitcitabine, and tenofovir alafenamide); NDA Infection in adults who have no antiretroviral treatment history or to replace the current antiretroviral regimen
GW Research Epidiolex (cannabidiol); NDA Seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome
Helsinn Healthcare Akynzeo (fosnetupitant and palonosetron); NDA To prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy
Janssen Pharmaceutical (Johnson & Johnson) Erleada (apalutamid); NDA Non-metastatic, castration-resistant prostate cancer
Medicines Development for Global Health Moxidectin (moxidectin); NDA Onchocerciasis due to Onchocerca volvulus in patients aged 12 years and older
Merck & Co. and Sun Pharmaceutical Ilumya (tildrakizumab); BLA Adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy
Rigel Pharmaceuticals Tavalisse (fostamatinib); NDA Thrombocytopenia (low blood platelet count) in adult patients with persistent or chronic immune thrombocytopenia
TaiMed Biologics USA Trogarzo (ibalizumab-uiyk); BLA HIV
Ultragenyx Pharmaceutical Crysvita (burosumab-twza); BLA To treat adults and children ages 1 year and older with x-linked hypophosphatemia, a rare, inherited form of rickets
US WorldMeds Lucemyra (lofexidine); NDA Non-opioid treatment for management of opioid withdrawal symptoms in adults
Vertex Pharmaceuticals Symdeko (tezacaftor and ivacaftor); NDA Cystic fibrosis in patients age 12 years and older

Novartis acquired Advanced Accelerator Applications in January 2018.

In August 2015, Amgen entered into a global collaboration with Novartis to jointly develop and commercialize treatments in the fields of migraine and Alzheimer's disease. The collaboration focuses on investigational Amgen drugs in the migraine field, including Aimovig. In April 2017, the collaboration was expanded to include co-commercialization of Aimovig in the US. For the migraine program, Amgen retains exclusive rights in Japan, and Novartis has exclusive rights in Europe, Canada, and rest of world

Array BioPharma has exclusive rights to Braftovi (encorafenib) and Mektovi (binimetinib) in the US and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea and Pierre Fabre exclusive rights to commercialize both products in all other countries, including in Europe, Asia, and Latin America.

Sun Pharmaceutical Industries Ltd.'s wholly owned subsidiary licensed worldwide rights to Ilumya (tildrakizumab) from a subsidiary of Merck & Co., Inc. in 2014. Funded by a Sun Pharma subsidiary, Merck & Co., Inc. was responsible for the completion of Phase-III trials and submission of a biologics license application to the US Food and Drug Administration (FDA) as well as manufacturing finished goods to support Sun Pharma's initial product launch. Sun Pharma is responsible for all post-approval regulatory activities, including subsequent submissions, pharmacovigilance, post approval studies, manufacturing, and commercialization of the approved product. Sun Pharma is also responsible for all regulatory, pharmacovigilance, post approval studies, manufacturing, and commercialization of approved products for all non-U.S. markets. Merck & Co is eligible to receive milestone payments and royalties on sales of Ilumya.

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

Table II: Small Molecule and Biologics New Molecular Entities Approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research, 2010 to 2017.
Year Number of New Molecular Entities (NMEs) Approved Percentage relative to total NME approvals and number of small molecules and biologics approved as NMEs
2010 21 NMEs approved 71% small molecules (15 NMEs)
29% biologics (6 NMEs)
2011 30 NMEs approved 77% small molecules (23 NMEs)
20% biologics (6 NMEs)
Plus 1 NME radioactive diagnostic imaging agent*
2012 39 NMEs approved

79% small molecules (31 NMEs)
15% biologics (6 NMEs)
Plus 2 NME radioactive diagnostic imaging agents**

2013 27 NMEs approved 81% small molecules (22 NMEs)
11% biologics (3 NMEs)
Plus 2 NME radioactive imaging agents***
2014 41 NMEs approved 71% small molecules (29 NMEs)
27% biologics (11 NMEs)
Plus 1 NME radioactive diagnostic imaging agent****
2015 45 NMEs approved* 71% small molecules (32 NMEs) and 1 insulin analog NME approved as a new drug application*****
27% biologics (12 NMEs)
2016 22 NMEs approved** 59% small molecules (13 NMEs)
32% biologics (7 NMEs)
Plus 2 NME radioactive diagnostic imaging agents******
2017 46 NMEs approved 74% small molecules (34 NMEs)
26% biologics (12 NMEs)

*In 2011, 23 small-molecule drugs and 1 radioactive diagnostic imaging were approved as new drug applications (NDAs).

**In 2012, 31 small-molecule drugs and 2 radioactive diagnostic imaging agents were approved as NDAs

***In 2013, 22 small-molecule drugs and 2 radioactive diagnostic imaging agents were approved as NDAs

T****In 2014, 29 small-molecule drugs and 1 radioactive diagnostic imaging agent were approved as NDAs .

*****In 2015, 32 small-molecule drugs were approved as NDAs and one insulin analog, Novo Nordisk's Tresiba (insulin degludec injection), a long-acting basal human insulin analog produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification was approved as a NDA, not as a biologics license application.

******In 2016, 13 small-molecule drugs and 2 diagnostic imaging agents were approved as NDAs.

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