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Biopharma gets groove back as Q1 approval of NMEs grows

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By Peter Winter
BioWorld Insight Editor

It looks as though the biopharmaceutical industry is back on track to make up for its poor return on research investments last year when only 22 new molecular entities (NMEs) received the FDA's green light, the fewest number for five years. In the first quarter of this year, 12 NMEs were approved, outperforming comparable periods since 2013. (See First quarter FDA approvals of new molecular entities, below.)

At that pace, the industry could be on target to beat the record total of 45 new medicines that were approved in 2015. (See BioWorld Insight, Dec. 27, 2016.)

The second quarter also got off to a good start with Teva Pharmaceutical Industries Ltd. gaining FDA approval for its Austedo (deutetrabenazine) as a treatment for chorea – involuntary, random and sudden, twisting and/or writhing movements – associated with Huntington's disease. The green light from the agency came approximately 10 months after the company had received an FDA complete response letter (CRL) for the drug's NDA. (See BioWorld Today, April 5, 2017.)

The vesicular monoamine transporter 2 (VMAT2) inhibitor was part of La Jolla, Calif.-based Auspex Pharmaceuticals Inc.'s drug portfolio, which Teva brought in-house following a $3.2 billion acquisition of the company in 2015.

That approval was quickly followed by Neurocrine Biosciences Inc.'s own VMAT2 inhibitor, Ingrezza (valbenazine), to treat adults with tardive dyskinesia, which was approved for marketing last week. (See BioWorld Today, April 13, 2017.)

According to the FDA, the efficacy of Ingrezza was shown in a clinical trial of 234 participants that compared Ingrezza to placebo. After six weeks, participants who received Ingrezza had improvement in the severity of abnormal involuntary movements compared to those who received placebo.

Several drugs targeting the central nervous system (CNS) were approved in the first quarter. (See New molecular entities approved in the U.S. in Q1:2017, below.)

For example, Newron Pharmaceuticals SpA received approval to market its Parkinson's disease (PD) drug, Xadago (safinamide), for patients who are currently taking levodopa/carbidopa and experiencing "off" episodes, or periods in which their medications are not working well, causing an increase in PD symptoms.

The company also had to respond to a CRL, which it received last March, in which the agency asked it to conduct a clinical evaluation of the potential abuse liability and dependence or withdrawal effects for the drug. (See BioWorld Today, March 31, 2016.)

Genentech, a unit of Roche Holding AG, of Basel, Switzerland, won FDA approval for Ocrevus (ocrelizumab) as the first disease-modifying drug for relapsing as well as primary progressive multiple sclerosis, the two forms most prevalent among patients at the time of diagnosis.

Two drugs indicated for constipation were also approved in the crop of first-quarter approvals. The market for that condition is large, with an estimated 42 million people affected, according to estimates from the NIH. Synergy Pharmaceuticals Inc.'s Trulance (plecanatide) received approval for the treatment of chronic idiopathic constipation in adult patients, and Shionogi Inc. and Purdue Pharma LP gained approval for Symproic (naldemedine) 0.2 mg tablets C-II as a once-daily oral peripherally acting mu-opioid receptor antagonist medication for the treatment of opioid-induced constipation in adult patients with chronic noncancer pain. Osaka, Japan-based Shionogi indicated that it has submitted a petition for the descheduling of Symproic to the U.S. Drug Enforcement Administration since the compound is currently a schedule II controlled substance being structurally related to naltrexone.

Among the cancer indications that were approved was Kisqali (ribociclib) in combination with an aromatase inhibitor as initial endocrine-based therapy for treatment of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor-2 negative advanced or metastatic breast cancer.

The oral cyclin-dependent kinase 4/6 pathway inhibitor, formerly known as LEE-011, was developed by the Novartis Institutes for Biomedical Research under a research collaboration with Astex Pharmaceuticals Inc., now part of Japan's Otsuka Pharmaceutical Co. Ltd.

The approval was based on a first-line phase III trial that met its primary endpoint early, demonstrating statistically significant improvement in progression-free survival compared to letrozole alone. (See BioWorld Today, March 14, 2017.)

PDUFA dates

In addition to the two NME's already across the goal line so far in the second quarter, the next few months could see as many as six more approvals based on the agency's scheduled PDUFA dates.

Eli Lilly and Co. and Incyte Corp. received a decision for baricitinib, their once-daily oral medication for the treatment of moderate to severe rheumatoid arthritis Friday and not the one they were hoping for. The FDA had extended the action date to allow time to review additional data analyses. Now the agency issued a CRL for the NDA. It indicates, the companies said, that additional clinical data are needed to determine the most appropriate doses. It also stated that additional data are necessary to further characterize safety concerns across treatment arms. (See BioWorld Today, April 17, 2017.)

Baricitinib is a once-daily oral JAK inhibitor currently in clinical studies for inflammatory and autoimmune diseases.

On the FDA PDUFA calendar, San Rafael, Calif.-based BioMarin Pharmaceutical Inc. is next up. The firm is expecting a decision on Brineura (cerliponase alfa), a recombinant human tripeptidyl peptidase 1 to treat children with CLN2 disease, a form of Batten disease. The action date is April 27, representing a delay of three months set by the agency, which requested an updated efficacy data cut from the company's ongoing extension study.

Investors are also anxiously waiting on Kenilworth, N.J.-based Merck & Co. Inc.'s supplemental biologics license application for Keytruda (pembrolizumab), its anti-PD-1 therapy, plus chemotherapy (pemetrexed plus carboplatin) for the first-line treatment of patients with metastatic or advanced nonsquamous non-small-cell lung cancer regardless of PD-L1 expression and with no EGFR or ALK genomic tumor aberrations. The combo therapy has been granted priority review by the FDA with a PDUFA date of May 10.

According to Leerink Partners LLC analyst Seamus Fernandez, "assuming MRK's chemo combo is approved with a broad label (as we expect) it should be well positioned to deliver low-double-digit EPS growth from 4Q:17 to mid-2018."

Radius Health Inc.'s abaloparatide-SC for postmenopausal osteoporosis was also hit by a delay when the FDA pushed the PDUFA date from March 30 to June 30. (See BioWorld Today, March 13, 2017.)

Nicox SA, of Sophia Antipolis, France, has a pending PDUFA date of Sept. 8 for a decision on its NDA for Zerviate (cetirizine ophthalmic solution) 0.24 percent, an eye drop formulation for the treatment of ocular itching associated with allergic conjunctivitis.