The pharmaceutical industry is on a record-setting pace for approvals of new molecular entities (NMEs) in 2018. Through early November, the FDA had approved 48 NMEs, already outpacing 2017’s recent high of 46 NME approvals and nearing the high mark of 53 NME approvals set in 1996. So which companies have made the regulatory cut, and what is the mix between small molecules and biologics?
Small molecules are dominating thus far, with 35 small-molecule NME approvals and 13 biologic-based NME approvals. Approximately 40% 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 November 1, 2018, The Center for Drug Evaluation and Research (CDER) of the US Food and Drug Administration (FDA) had approved 48 NMEs (see Table I at the end of article), already surpassing the 46 NMEs approved in 2017, which was second only to the 53 NMEs approved in 1996. Although NME approvals do not necessarily follow a chronological track with more than one month remaining in calendar year 2018 and withadditional approvals often made at the end of year, 2018 has the potential to be a record-setting year for NME approvals.
The uptick in NME approvals in 2017 and now again in 2018 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. Small molecules are dominating thus far, with 35-small molecule NME approvals and 13 biologic-based NME approvals, which includes one antibody drug conjugate (ADC). This product mix in 2018 is consistent with NME approvals in 2017. The 35 small molecules approved thus far in 2018 represents 73% of NME approvals; in 2017, small-molecule NME approvals accounted for 75% of new drug approvals (see Table II at end of article). Biologic-based drugs have accounted for 17% of NMEs approvals thus far in 2018 compared to 15% for all of 2017.
The large pharmaceutical companies with biologic-based drug approvals thus far in 2018 include: Amgen’s Aimovig (erenumab-aooe), a drug to prevent migraines in adults; AstraZeneca’s Lumoxiti (moxetumomab pasudotox-tdfk), an ADC for treating hairy cell leukemia; Eli Lilly and Company’s Emgality (galcanezumab-gnlm) for the preventive treatment of migraine in adults; Merck & Co.’s and Sun Pharmaceutical’s Ilumya (tildrakizumab) for treating moderate-to-severe plaque psoriasis; and Teva Pharmaceutical Industries’ Ajovy (fremanezumab-vfrm) for the preventive treatment of migraine in adults. Table I at the end of the article summarizes all biologic and small-molecule NME approvals thus far in 2018.
Big Pharma and NME approvals
Of the 48 NME approvals thus far in 2018, 19, or 40%, were from the pharmaceutical majors (see Table I). Pfizer led all companies with three NME approvals. AstraZeneca, Eli Lilly and Company, Merck & Co., and Shionogi each had two NME approvals. AbbVie, Allergan, Amgen, Gilead Sciences, GlaxoSmithKline, Johnson & Johnson’s Janssen Pharmaceutical, Novartis (through its acquisition of Advanced Accelerator Applications in January 2018), and Teva each had one (see Table I).
|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 November 2, 2018.|
|Company||Brand name (active ingredient); application type||Indication|
|AbbVie||Orilissa (elagolix sodium); NDA||Moderate-to-severe pain associated with endometriosis|
|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|
|Agios Pharmaceuticals||Tibsovo (ivosidenib); NDA||Relapsed or refractory acute myeloid leukemia|
|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|
|Allergan||Seysara (sarecycline); NDA||Inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older|
|Alnylam Pharmaceuticals||Onpattro (patisiran); NDA||Polyneuropathy of hereditary transthyretin-mediated amyloidosis in adult patients|
|Amgen||Aimovig (erenumab-aooe); BLA||Preventive treatment of migraines in adults|
|Amicus Therapeutics||Galafold (migalastat); NDA||Adults with Fabry disease|
|Array BioPharma||Braftovi (encorafenib); NDA||Unresectable or metastatic melanoma|
|Array BioPharma||Mektovi (binimetinib); NDA||Unresectable or metastatic melanoma|
|AstraZeneca||Lumoxiti (moxetumomab pasudotox-tdfk); BLA||Hairy cell leukemia|
|AstraZeneca||Lokelma (sodium zirconium cyclosilicate); NDA||Hyperkalemia (high potassium levels)|
|Biocodex SA||Diacomit (stiripentol); NDA||Seizures associated with Dravet syndrome in patients 2 years of age and older taking clobazam|
|BioMarin Pharmaceutical||Palynziq (pegvaliase-pqpz); BLA||Phenylketonuria (inherited disorder that increases the levels of phenylalanine in the blood)|
|Dompe Farmaceutici||Oxervate (cenegermin-bkbj); BLA||Neurotrophic keratitis|
|Dyax Corp.||Takhzyro (lanadelumab); BLA||Types I and II hereditary angioedema|
|Eli Lilly and Company||Emgality (galcanezumab-gnlm); BLA||For the preventive treatment of migraines in adults|
|Eli Lilly and Company||Olumiant (baricitinib); NDA||Moderately to severely active rheumatoid arthritis|
|Fresenius Kabi||Omegaven (fish oil triglycerides); NDA||A source of calories and fatty acids in pediatric patients with parenteral nutrition-associated cholestasis|
|Gilead Sciences||Biktarvy (bictegravir, embitcitabine, and tenofovir alafenamide); NDA||HIV-1 infection in adults who have no antiretroviral treatment history or to replace the current antiretroviral regimen|
|GlaxoSmithKline||Krintafel (tafenoquine); NDA||Radical cure (prevention of relapse) of Plasmodium vivax malaria|
|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|
|Ionis Pharmaceuticals||Tegsedi (inotersen); NDA||Polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults|
|Janssen Pharmaceutical (Johnson & Johnson)||Erleada (apalutamid); NDA||Non-metastatic, castration-resistant prostate cancer|
|Kyowa Kirin||Poteligeo (mogamulizumab-kpkc); BLA||Two rare types of non-Hodgkin lymphoma|
|Leadiant Biosciences||Revcovi (elapegademase-lvlr); BLA||Adenosine deaminase-severe combined immunodeficiency (ADA-SCID)|
|Medicines Development for Global Health||Moxidectin (moxidectin); NDA||Onchocerciasis due to Onchocerca volvulus in patients aged 12 years and older|
|Merck & Co.||Pifeltro (doravirine); NDA||HIV-1 infection in adult patients|
|Merck & Co. and Sun Pharmaceutical||Ilumya (tildrakizumab); BLA||Adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy|
|Paratek Pharmaceuticals||Nuzyra (omadacycline); NDA||Community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections|
|Pfizer||Lorbrena (loratinib); NDA||Patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer|
|Pfizer||Talzenna (talazoparib); NDA||Locally advanced or metastatic breast cancer patients with a germline BRCA mutation|
|Pfizer||Vizimpro (dacomitinib); NDA||Metastatic non-small-cell lung cancer|
|Regeneron Pharmaceuticals||Libtayo (cemiplimab-rwlc); BLA||Cutaneous squamous cell carcinoma|
|Rigel Pharmaceuticals||Tavalisse (fostamatinib); NDA||Thrombocytopenia (low blood platelet count) in adult patients with persistent or chronic immune thrombocytopenia|
|Shionogi||Mulpleta (lusutrombopag); NDA||Thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure|
|Shionogi||Xofluza (baloxavir marboxil); NDA||Acute uncomplicated influenza in patients who have been symptomatic for no more than 48 hours|
|Siga Technologies||Tpoxx(tecovirimat); NDA||Smallpox|
|TaiMed Biologics USA||Trogarzo (ibalizumab-uiyk); BLA||HIV|
|Tetraphase Pharmaceuticals||Xerava (eravacycline); NDA||Complicated intra-abdominal infections in patients 18 years of age and older|
|Teva Pharmaceutical Industries||Ajovy (fremanezumab-vfrm); BLA||For the preventive treatment of migraines in adults|
|TherapeuticsMD||Annovera (segesterone acetate and ethinyl estradiol vaginal system); NDA||New vaginal ring used to prevent pregnancy for an entire year|
|Verastem||Copiktra (duvelisib); NDA||Relapsed or refractory chronic lymphocytic leukemia, small lymphocytic lymphoma and follicular lymphoma|
|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 the 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.
****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.
A Product Manager with expertise in pharma marketing and sales operations