After a flurry of activity in December, when the FDA approved seven new molecular entities (NMEs), the total of novel drugs that were given the green light this year reached 48, a number that ranks third behind the record 59 new medicines the agency approved last year and 53 in 1996. Over the past three decades, the FDA has approved 924 novel medicines, averaging out to approximately 30 per year.  The present decade yielded an above average of 38 NMEs compared to an average of 23 in the 2000-2009 decade and 31 average in the 1990-1999 period. The biopharma sector can point to the massive $400 billion invested into R&D during this decade, along with the evolution of new technologies, that has helped move the needle for new medicines approved. This is particularly evident in the past three years, during which 40% of the decade’s total of 378 NMEs were approved. 

Migraine treatments 

The high incidence of migraine, which the FDA said is three times more common in women than in men and affects more than 10% of people worldwide, has led to five new treatments in the past two years. The introduction of new therapies will be welcomed because no new therapies, either for acute treatment or prevention, had reached the market for almost a decade. According to Billy Dunn, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, “Migraine is an often-disabling condition that affects an estimated 37 million people in the U.S.” He was commenting in an announcement that Dublin-based drugmaker Allergan plc had received approval for its oral calcitonin gene-related peptide receptor (CGPR) antagonist, Ubrelvy (ubrogepant) for the acute treatment of migraine with or without aura in adults. The drug was licensed by Allergan with another CGRP receptor agonist from Merck & Co. Inc. in 2015. 

The migraine treatment followed an October approval of Eli Lilly and Co.’s Reyvow (lasmiditan) tablets for the same condition. The pharma gained the drug when it acquired Colucid Pharmaceuticals Inc. for nearly $1 billion in early 2017. 

Reyvow is the first FDA-approved medicine in a new class of acute migraine treatment (serotonin 5-HT1F receptor agonists) that binds to 5-HT1F receptors and expands Lilly's existing migraine franchise, which includes last year’s approval of Emgality (galcanezumab-gnlm) solution (300 mg) for injection for treating episodic cluster headache in adults. Also last September, the FDA approved, as preventive treatments of migraine, Teva Pharmaceutical Industries Ltd.'s Ajovy (fremanezumab-vfrm) and, in May 2018, Novartis AG and Amgen Inc.'s Aimovig (erenumab-aooe). 

SVB Leerink Research analyst Marc Goodman said he believes the approval of Ubrelvy, with a favorable label that has no black box warning for liver toxicity, “bodes well for the class and also for Biohaven’s rimegepant (another oral CGRP/calcitonin gene-related peptide), which is close behind on the approval decision docket (1Q20).” 

By the numbers 

It appears that innovative success, in terms of new medicines approved, continues to be skewed in favor of biotech companies. Last year, for example, biotechs gained 39 of the record 59 FDA NME approvals. 

It was the same situation this year, with less than half of the 2019 new medicines brought to market by big pharma companies. Novartis did well with five approvals, including Adakveo (crizanlizumab) to reduce the frequency of vaso-occlusive crises (VOCs), or pain crises, in adult and pediatric patients ages 16 and older with sickle cell disease (SCD). It was the first FDA-approved drug in SCD that binds to P-selectin, a cell adhesion protein that plays a key role in multicellular interactions that can lead to VOCs. 

Interestingly, less than two weeks after the go-ahead for Adakveo, the FDA cleared – well ahead of its Feb. 26, 2020, PDUFA date – Oxbryta (voxelotor), from Global Blood Therapeutics Inc., for SCD in adults and pediatric patients ages 12 and older. The drug is an inhibitor of deoxygenated sickle hemoglobin polymerization, the main abnormality in SCD. It makes cells less likely to bind together and form the distinctive sickle shape, leading to low hemoglobin levels due to red blood cell destruction.   

Several pharmas scored two approvals, including Abbvie Inc. with its oral rheumatoid arthritis (RA) drug, upadacitinib, which won U.S. approval following a priority review at the FDA. The potential blockbuster JAK1 inhibitor, to be marketed as Rinvoq, is indicated for adults with moderate to severe RA who have had an inadequate response or intolerance to methotrexate. 

Rinvoq is Abbvie’s second targeted immunomodulator after Skyrizi (risankizumab), a medicine that won FDA approval for adults with moderate to severe plaque psoriasis in April. The company paid Boehringer Ingelheim GmbH $595 million up front for rights to the anti-IL-23 therapy and another asset in 2016.  

Imaging agents, diagnostics and dyes 

Making the novel medicines list this year were several non-drug compounds used in the diagnosis of disease, including Gallium-68-DOTATOC injection. Following an NDA submitted by the University of Iowa Health, it was approved for use with positron emission tomography (PET) for localization of somatostatin receptor-positive neuroendocrine tumors in adult and pediatric patients. 

After more than seven years, the Fluorodopa F 18 PET scan used to diagnose Parkinsonian syndromes received the green light from the FDA. The Feinstein Institute for Medical Research first submitted an NDA for the scan back in 2012.  

IQ Medical Ventures received approval for Exem foam as a diagnostic agent used to assess fallopian tube patency in women with known or suspected infertility. 

Also receiving approval was Tissueblue (Brilliant Blue G ophthalmic solution) following an NDA submission by the Dutch Ophthalmic Research Center (DORC). The compound is indicated for selectively staining the internal limiting membrane (ILM) which forms the inner layer of the retina. Cellular proliferation on the ILM can lead to the formation of vision-impairing epiretinal membranes and macular holes. The transparent nature of the ILM makes it difficult to visualize and remove. DORC explained that Tissueblue ophthalmic solution is intended to be injected onto the inner retinal surface, enabling the ILM to be clearly stained and distinguished from unstained retina, thereby facilitating removal. 

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