Investors cooled on biopharma company equities, particularly in the final quarter of the year, with the BioWorld Biopharmaceutical Index slipping 11 percent in value during the period. While most companies will be glad to see the back of a turbulent year, some did manage to eke out respectable gains, mainly on achieving product approvals or signing lucrative partnership deals with big pharma companies. In this feature, we provide the top and bottom rankings from an analysis of the annual performances of all the public biopharma companies that are being tracked weekly by BioWorld. To be included in the study, a company's stock price had to be above $2 at the beginning of 2018.

Topping the gainers list was Dublin-based Amarin Corp. plc (NASDAQ:AMRN), whose 239 percent gain in its share value was earned mainly in September on news of its Vascepa cardiovascular (CV) outcomes trial. (See BioWorld, Sept. 25, 2018.)

Approved in 2012, the drug is an ethyl ester of eicosapentaenoic acid given as an adjunct to diet to cut back triglyceride (TG) levels in adult patients with severe hypertriglyceridemia. The global Reduce-It study in 8,179 statin-treated adults with elevated CV risk met its primary endpoint, yielding a 25 percent lower risk of major adverse CV events in the intent-to-treat patient population to a high degree of statistical significance (p<0.001).

The company presented full details of the primary results from the trial at the 2018 Scientific Sessions of the American Heart Association in Chicago in November. They confirmed a 25 percent relative risk reduction for the top-line primary endpoint result with multiple robust demonstrations of efficacy, including 20 percent reduction in cardiovascular death.

Cardiovascular benefits appeared not to be influenced significantly by TG levels at baseline (135 mg/dL to 499 mg/dL baseline range) or as achieved at one year, suggesting mechanisms at work with use of Vascepa that are independent of triglyceride reduction.

Blockbuster deal

A major deal helped the shares of Pasadena, Calif.-based Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR) gain 237 percent in the year, good for the second spot. (See Top 20 companies ranked by annual share price gain in 2018, below.)

The company's third-generation hepatitis B virus (HBV) candidate, ARO-HBV, designed to silence the entire HBV transcriptome, intervening upstream of the reverse transcription process that standard-of-care nucleotide and nucleoside analogues affect, attracted the attention of Janssen Pharmaceuticals Inc., a unit of Johnson & Johnson, of New Brunswick, N.J., which entered an exclusive license and collaboration deal with Arrowhead covering development and commercialization of ARO-HBV. (See BioWorld, Oct. 5, 2018.)

Arrowhead also agreed to a research collaboration and option arrangement for up to three additional RNAi therapeutics against targets selected by Janssen. The potential candidates will leverage Arrowhead's Targeted RNAi Molecule, or TRiM platform. In return, the company received $175 million up front plus a $75 million equity investment. The deal could be worth up to $3.7 billion factoring in the achievement of all the downstream milestones.

Regenerative medicine is hot

The heightened interest in companies working in regenerative medicine helped move the shares of Osiris Therapeutics Inc. (NASDAQ:OSIR), which gained the third spot in our rankings with a 125 percent annual increase in value.

Fate Therapeutics Inc. (NASDAQ:FATE) also saw its share value double in 2018. The company is developing programmed cellular immunotherapies for cancer and immune disorders, In November, it announced that the FDA had allowed its IND application for FT-500, a universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line. The trial of FT-500 is expected to be the first-ever clinical investigation in the U.S. of an iPSC-derived cell product, the company said.

Rare diseases

Shares of Ra Pharmaceuticals Inc. (NASDAQ:RARX), rose 114 percent in the year on the strength of positive results for its lead candidate in a midstage study for the treatment of myasthenia gravis (MG).

RA-101495 (more recently known as zilucoplan), self-administered subcutaneously once per day, is a synthetic, macrocyclic peptide discovered by the company. It binds complement component 5 (C5) with subnanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative or lectin pathways, the company said. Potentially adding to the benefit, by binding to a region of C5 corresponding to C5b, zilucoplan disrupts the interaction between C5b and C6 to prevent assembly of the membrane attack complex.

Cambridge, Mass.-based Ra finished dosing of the phase II study in generalized MG at the end of October, and the company said it was pleased with the 98 percent of enrolled patients (n=43/44) that converted from the 12-week phase II portion into the long-term extension study. The primary endpoint of the experiment is change from baseline in Quantitative Myasthenia Gravis test score at 12 weeks, with the secondary endpoint change in MG-Activities of Daily Living scale. (See BioWorld, Dec. 3, 2018.)

Based on its improving share value, the company was able to price an underwritten public offering in December that is expected to gross approximately $130 million, excluding any exercise of the underwriters' option to purchase additional shares.

It intends to use the net proceeds from the offering, in addition to its existing cash resources, to fund the clinical development of zilucoplan, including the phase III program in MG and the advancement of other pipeline programs, and for working capital and other general corporate expenses.

Challenging year

The group of leading decliners, for the most part, either came up short in their clinical trials programs, received complete response letters (CRLs) from the FDA, or got caught up in the general market's downturn with investors shying away from small and medium-sized biopharma companies. (See Leading decliners in 2018, below.)

In the fourth quarter of 2017, New Haven, Conn.-based Melinta Therapeutics Inc. (NASDAQ:MLNT) completed its reverse merger with Cempra Inc. to become a publicly traded company. Immediately following the quarter, it acquired the infectious disease business of The Medicines Co., including products Vabomere (meropenem and vaborbactam), Orbactiv (oritavancin) and Minocin (minocycline) for injection, and as a result became a pure-play antibiotics company with the products adding to its own Baxdela (delafloxacin), indicated in adults for treatment of acute bacterial skin and skin structure infections caused by susceptible bacteria, which received FDA approval in June 2017. At the beginning of 2018, the company's shares were trading at $15.80 but since then they have steadily slipped to close out the year down 95 percent.

Shares of Gtx Inc. (NASDAQ:GTXI) dropped dramatically after a phase II trial found two doses of its sole clinical candidate, a selective androgen receptor modulator, failed to separate from placebo in helping postmenopausal women reduce stress urinary incontinence. The candidate, enobosarm, has been evaluated in 27 trials to date. Barring a compelling finding in the full data, the program will likely be wound down, the company said. (See BioWorld, Sept. 24, 2018.)

In November, Watertown, Mass.-based Aileron Therapeutics Inc. (NASDAQ:ALRN) entered a clinical trial collaboration with Pfizer Inc. to evaluate the combination of its ALRN-6924 and the pharma's Ibrance (palbociclib) in MDM2-amplified cancers. The company expects the phase Ib trial to start enrolling patients with solid tumors in the first quarter. ALRN-6924 is a first-in-class, stabilized cell-permeating peptide that mimics the p53 tumor suppressor protein to disrupt the interaction with both its endogenous inhibitors, MDMX and MDM2. Despite that news, the company's share value did not get much of an uptick. During the year, the share value dropped 92 percent.

Flex Pharma Inc., whose shares (NASDAQ:FLKS) fell about 90 percent in the year, announced last week that it was planning to merge with Salarius Pharmaceuticals LLC, a clinical-stage oncology company targeting the epigenetic causes of cancers.

Salarius reported it had completed a $6.4 million private placement, which combined with cash from Flex Pharma, is expected to fund the combined company to mid-2020, allowing it to report early cohort data from an ongoing phase I Ewing sarcoma trial. The merged company will be renamed Salarius Pharmaceuticals Inc.

Salarius' lead compound, seclidemstat, a differentiated, reversible inhibitor of the lysine-specific demethylase 1 enzyme, targets the epigenetic dysregulation underlying Ewing sarcoma.

Gemphire Therapeutics Inc., of Livonia, Mich., which is focused on developing and commercializing therapies for cardiometabolic disorders, including dyslipidemia and nonalcoholic steatohepatitis, said in December it was conducting a review of a range of strategic alternatives focused on maximizing stockholder value. The company's share value (NASDAQ:GEMP) has dropped 90 percent since the beginning of 2018.

In August, the company's gemcabene, which had previously been given to about 1,200 adult patients in 25 phase I and phase II trials for up to 12 weeks without any drug-related severe adverse events, hit a snag as the data and safety monitoring board overseeing a phase IIa study in pediatric subjects recommended the study be stopped because patients apparently were getting sicker. (See BioWorld, Aug. 13, 2018.)

Also, with additional preclinical data on gemcabene now being required by the FDA, the company said its planned phase III programs, initially focused in hypertriglyceridemia, are expected to start later than originally planned.

The company added that it continues to make progress with the ongoing preclinical studies with the goal of providing the FDA with the data it requires to lift the partial clinical hold on gemcabene. Results are expected to be provided to the agency in the second half of this year.