The biopharmaceutical sector limps into the New Year bidding farewell to periods of significant market turbulence and intense public, media and political pressure brought about by the perceived high price tags for drugs. Add in mixed financial performances, drug failures and a smaller number of new drugs being approved and it is no wonder that the sector's collective equities finished down 20 percent in value, closing its doors on what will go down as one of the sector's worst performing 12 months in the past several years.
Both the BioWorld Drug Developers Index and BioWorld Biopharmaceutical Index slipped in value in December, down 5 percent and 0.5 percent, respectively. For the year, the Drug Developers Index closed down 15 percent and the Biopharmaceutical Index recorded an 18.5 percent loss. In comparison, the general markets had a great year with the Dow Jones Industrial Average and the Nasdaq Composite index closing 2016 up 14 and 8.5 percent, respectively.
Despite the challenging year for the biopharmaceutical sector, five companies recorded a doubling or greater of their share prices. (See Top 20 companies by share price gain, right.)
Cambridge, Mass.-based Colucid Pharmaceuticals Inc. (NASDAQ:CLCD) took the top prize as the leading gainer with a massive 340 percent jump in its share price. Investors were impressed with the firm's top-line phase III migraine data with lasmiditan tablets, hitting the primary endpoint of two hours' freedom from headache in the study known as SAMURAI. The company said SAMURAI achieved the primary and key secondary efficacy endpoints with statistical significance (p < 0.001). (See BioWorld Today, Sept. 7, 2016.)
Lasmiditan is indicated for the acute treatment of migraine headaches in adults without the vasoconstrictor activity associated with previous generations of migraine therapies. It selectively targets 5-HT1F receptors expressed in the trigeminal pathway of the central nervous system.
The company has a second pivotal trial in progress – designated SPARTAN – in which more than 50 percent of the 2,968 migraine patients expected to enroll have now been randomized. The objective of the study is to evaluate the safety and efficacy of lasmiditan (50 mg, 100 mg and 200 mg) in comparison to placebo two hours after dosing on freedom from migraine headache pain, which is the primary endpoint, and on freedom from the most bothersome associated symptom of migraine (nausea, phonophobia or photophobia), which is the key secondary endpoint.
Last year's top gainer, Exelixis Inc., whose shares soared an incredible 297 percent, had another great year, seeing its shares (NASDAQ:EXEL) increase in value by 164 percent, enough to secure second spot in the top 20 list.
It was fueled in large part by the FDA approval of Cabometyx (cabozantinib) for advanced renal cell carcinoma patients who have received prior anti-angiogenic therapy. (See BioWorld Today, April 26, 2016.)
Cabometyx is a tyrosine kinase inhibitor designed to hit several targets, including MET, AXL and three VEGF receptors. The drug is partnered outside the U.S., Canada and Japan with Paris-based Ipsen SA, which paid $200 million up front in a potential $855 million deal involving all indications. (See BioWorld Today, March 2, 2016.)
Findings from the phase III NOVA trial of niraparib in women with recurrent ovarian cancer helped shares (NASDAQ:TSRO) of drug developer Tesaro Inc. reach the third spot in the top 20 list, with a 158 percent increase. Back in June the company reported the trial achieved its primary endpoint of statistically significant progression-free survival (PFS) compared to control across germline BRCA mutation (gBRCAmut) carriers and non-gBRCAmut carriers, including those with homologous recombination deficient (HRD) tumors. The HRD+ non-gBRCAmut carriers were identified by the Mychoice HRD companion diagnostic developed by Myriad Genetics Inc. (See BioWorld Today, June 30, 2016.)
Late in December, the Waltham, Mass.-based company reported that the FDA had granted priority review for the niraparib new drug application (NDA). Niraparib is a PARP inhibitor that is being evaluated as a potential new treatment option for patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer following response to platinum-based chemotherapy. The agency has established a PDUFA of June 30, 2017, and is not currently planning to hold an advisory committee meeting to discuss the application.
Regulatory success also helped double the value of Achaogen Inc.'s shares. Its NDA filing with the FDA is expected in the second half of 2017, after the phase III EPIC (Evaluating plazomicin in cUTI) registration trial of lead candidate plazomicin met the agency's objective of noninferiority compared to meropenem in patients with complicated urinary tract infections and acute pyelonephritis. The trial also showed superiority in the EMA's primary efficacy endpoints of microbiological eradication at the test-of-cure visit in both the microbiological modified intent-to-treat population and in the microbiologically evaluable (ME) population, with a marketing authorization application filing in the EU expected in 2018. (See BioWorld Today, Dec. 13, 2016.)
Plazomicin is an aminoglycoside designed to overcome most clinically relevant aminoglycoside resistance mechanisms, enabling the treatment of serious bacterial infections due to multidrug-resistant Enterobacteriaceae, including carbapenem-resistant Enterobacteriaceae.
Shares of Array Biopharma Inc. (NASDAQ:ARRY) doubled over the year, helped by news that the first part of its phase III COLUMBUS trial in BRAF-mutant melanoma met its primary endpoint. The statistically significant median PFS benefit for patients treated with a combination of two of the company's drugs, the MEK inhibitor binimetinib and the BRAF inhibitor encorafenib, was 14.9 months vs. 7.3 months for Roche Holding AG's Zelboraf (vemurafenib) alone. Global regulatory submissions for the new combination are planned to take place this year.
An illustration of the tough year experienced by public biopharma companies listed on U.S. stock exchanges is evidenced by the fact that 75 percent of them saw their shares decline in value. The group of leading decliners, for the most part, either came up short in late-stage clinical trials or received complete response letters (CRLs) from the FDA. (See Leading decliners in 2016, right.)
New York-based Ophthotech Corp., for example, saw its shares (NASDAQ:OPHT) plummet 86.4 percent in just one day last month on news that the pre-specified primary endpoint of mean change in visual acuity at 12 months, measured as best corrected visual acuity in terms of additional letter gains, was not achieved in its two pivotal phase III trials investigating the superiority of Fovista (pegpleranib) anti-PDGF therapy in combination with Lucentis (ranibizumab) anti-VEGF therapy compared to Lucentis monotherapy for the treatment of wet age-related macular degeneration. (See BioWorld Today, Dec. 13, 2016.)
It has been a tough couple of months for Chapel Hill, N.C.-based Cempra Inc., whose share value (NASDAQ:CEMP) has slipped 91 percent. In November, its shares got hit when the FDA released its briefing documents ahead of an advisory committee meeting on its oral and I.V. formulations of lead candidate Solithera (solithromycin). The documents flagged the potential for liver injury with its use. A month later the company reported it had received a CRL from the agency relating to its NDAs for oral and I.V. solithromycin for the treatment of community-acquired bacterial pneumonia (CABP) in adults.
The CRL noted that additional clinical safety information and the satisfactory resolution of manufacturing facility inspection deficiencies are required before the applications may be approved.
The FDA determined the risk of hepatotoxicity had not been adequately characterized and recommended a comparative study of approximately 9,000 patients to evaluate the safety of solithromycin in patients with CABP. (See BioWorld Today, Nov. 3, 2016, and Dec. 30, 2016.)
During the June ASCO meeting, shares of Pronai Therapeutics Inc., of Vancouver, British Columbia, were hit hard following disappointing interim results from its Wolverine phase II trial of PNT2258 for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Although modest efficacy was observed, the company's president and CEO, Nick Glover, said at the time that "we do not view these results as robust enough to justify continued development of the drug in DLBCL."
Biopharma companies certainly have to deal with binary events as they progress their product pipelines. Investors have not been kind to those that have reported negative news in 2016. Recovery for those companies will depend on a number of factors, among them being the depth of their pipelines and the cash they have in the bank to drive those programs forward.
Editor's note: In next week's issue, we will be providing an in-depth analysis on the financial performance of the sector for 2016 and looking ahead at the industry's prospects for the next 12 months.