The FDA approved The Medicines Co.'s antibiotic Orbactiv (oritavancin) after the market close Wednesday, making the acute care specialist the latest player to market a product to treat acute bacterial skin and skin structure infections (ABSSSIs) outside hospitals, where multi-day stays can lead to big bills for both patients and payers.

The therapy is approved to treat ABSSSIs caused by gram-positive microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Its label includes a warning regarding interference with coagulation tests and interaction with warfarin, a drug used to prevent blood clots.

"The approval of several new antibacterial drugs this year demonstrates that we are making progress in increasing the availability of treatment options for patients and physicians," said Edward Cox, director of the FDA's Office of Antimicrobial Products. "However, more work is needed in this area, and the FDA remains a committed partner to help promote the development of antibacterial drugs."

With the FDA's favor, Orbactiv becomes the second long-acting antibiotic approved to treat ABSSSI following the FDA's May 23 approval of Dalvance (dalbavancin), developed by Durata Therapeutics Inc., and the third qualified infectious disease product (QIDP) to win approval following Cubist's Sivextro (tedizolid phosphate) in June. (See BioWorld Today, May 27, 2014, and June 24, 2014.)

Medicines CEO Clive Meanwell told investors July 23 that manufacturing and supply chain resources for Orbactiv are in place, but that it might take some time to drive adoption of the product, conceding that after numerous hospital launches during his career, "it is probably best not to assume speed at the beginning."

The company has yet to set pricing for Orbactiv, but Meanwell noted on the company's July 23 earnings call that his company is paying close attention to Cubist and Durata's strategies. Dalvance is priced at a premium to Cubicin, while Sivextro is priced roughly in line with Pfizer Inc.'s oxazolidinone drug Zyvox (linezolid), noted Bank of America analyst Steve Byrne. Picking the right price for Orbactiv will take a little time, Meanwell said.

"As a general rule, we like to look at the value of the products that we launch in absolute terms for the hospital," Meanwell said. "Before we really can comment on our pricing strategy, I think we would really like to see the outcome of the FDA process and make sure we know what is on the label, so that we can do the right thing for our customers."

Orbactiv was approved based on data from two trials, which showed that a single 1,200-mg dose of Orbactiv was non-inferior to twice-daily intravenous dosing of vancomycin given for seven to 10 days in patients with acute bacterial skin and skin structure infections caused or suspected to be caused by such gram-positive bacteria including MRSA.

BIG NEED, CROWDED MARKET

Medicines, of Parsippany, N.J., added Orbactiv to its portfolio in February 2009 when it acquired Targanta Therapeutics Corp. for about $42 million. At the time, Medicines cited 2007 data pegging the U.S. hospital market for gram-positive infections at $1.1 billion and growing.

An estimated 5.2 million patients in the U.S. and Western Europe are admitted to hospitals with ABSSSIs annually, Medicines found. Patients often receive intravenous therapies that require hospital admission and multi-day dosing, according to Pharmerit International researchers who joined colleagues in evaluating recent trends in U.S. hospital admissions.

Given the need and opportunity, Medicines' efforts put it in good company. In addition to Dalvance and Sivextro, it will be facing down Cubist's Cubicin (daptomycin); quinupristin/dalfopristin; Theravance Inc.'s Vibativ (telavancin); Sanofi-Aventis' teicoplanin, ceftaroline, which is marketed by Forest, Astrazeneca plc and Dainippon Sumitomo Pharma Co. Ltd.; and Pfizer Inc.'s tigecycline.

Despite the crowded field, Medicines' expects that Orbactiv's single 1,200-mg dose regimen will give it an edge, by helping "eliminate the need for daily infusions and potentially reduce the need for patient hospitalization, outpatient infusion services or central intravenous access," it noted in a recent regulatory filing. By contrast, Dalvance is given in a two-dose regimen, first in a 1,000-mg injection followed one week later by 500-mg injection. Sivextro is administered once daily for six days.

In addition, thanks to its November 2013 QIDP designation, Medicines has an additional five years of marketing exclusivity in the U.S., protecting it until at least 2025.

A PAYOFF TO COME

Under the terms of its acqusition of Targanta, Medicines was on the hook for up to $90.4 million in the aggregate milestone payments. Since certain milestones were missed, that obligation has fallen.

But Medicines will still owe former Targanta shareholders $49.4 million should aggregate net sales of Orbactiv reach or exceed $400 million in four consecutive calendar quarters ending on or before the end of 2021. It will also owe $40 million in additional payments to other unnamed third parties.

WHAT'S NEXT

While Medicines developed Orbactiv for the treatment of ABSSSI, it's also exploring the antibiotic's application in other indications, including for the treatment of Clostridium difficile, prosthetic joint infections, anthrax and other gram-positive bacterial infections.

Beyond Orbactiv, Medicines has three remaining products in line for potential approval during the next 12 to 18 months. With its purchase of Rempex Pharmaceuticals Inc., it acquired Carbavance, also known as RPX-7009, an experimental therapy for gram-negative bacterial infections.

A re-filing of the intravenous antiplatelet agent cangrelor for the reduction of thrombotic cardiovascular events also is in the works following an FDA complete response letter earlier this year. Meanwhile, Fibrocaps, a dry powder topical formulation of fibrinogen and thrombin, has a Jan. 31, 2015, PDUFA date. (See BioWorld Today, Aug. 7, 2013, and May 2, 2014.)

It's too early to say whether Orbactiv and the other potential approvals will be enough to make up for revenue lost to Angiomax (bivalirudin) generics when they begin to appear on the market between 2015 and 2019, noted Adnan Butt, an analyst at RBC Capital Markets LLC. But with high expectations for the potential of Medicines pipeline, he gave the company an "outperform" rating on July 23.

The FDA's decision came after Wednesday's market close, when MDCO shares finished the day at $23.79, for a gain of 13 cents. In after hours trading, the stock edged up 9.5 percent on the news.