BioWorld Insight Contributing Writer

It seems big pharma may be coming back to antibiotics, a treatment area they previously left for dead.

Last month, Rib-X Pharmaceuticals Inc. inked a discovery deal with Sanofi SA to develop at least four antibiotics to treat resistant Gram-positive and resistant Gram-negative pathogens.

Sanofi paid $19 million last month with the potential for development and regulatory milestones of up to $86 million and commercial milestones potentially exceeding $100 million for each product. (See BioWorld Today, July 7, 2011.)

Later in the month, Trius Therapeutics Inc. snagged Bayer Pharma AG as a development partner for its Phase III antibiotic torezolid phosphate.

Bayer gains rights to the antibiotic in countries in Asia, Africa, Latin America and the Middle East, excluding North and South Korea, in exchange for $25 million up front and footing the bill for approximately 25 percent of future development costs required for global approval in acute bacterial skin and skin structure infections (ABSSSI) and pneumonia.

Prabhavathi Fernandes, president and CEO of Cempra Pharmaceuticals Inc., isn't convinced the recent deals are an absolute sign that pharma is returning to antibiotics, but she's confident large companies will return eventually. "This is the way it has been for a very long time. Companies get in and get out," Fernandes said.

This time around, Fernandes sees pharma's motivation as a simple need for additional revenue.

"It's all product-driven," Fernandes said.

Renewing Market

Pharma's exit from the antibiotic space was predicated on its push toward blockbuster drugs. It's more difficult to achieve blockbuster status with a drug that treats acute conditions, like an antibiotic, than with one for chronic indications.

However, higher prices fetched by new drugs such as Optimer Pharmaceuticals Inc.'s Dificid (fidaxomicin) have proven that it's possible to make money in the antibiotic space.

While Optimer just launched Dificid last month and has yet to report revenues, analysts say the drug's price of $2,800 for a 10-day course of treatment will translate into healthy sales, perhaps in the quarter-of-a-billion-dollar range.

"You probably will not make $8 billion to $10 billion, but you will certainly have the size of a small cancer market," Fernandes said. "As long as the antibiotics can be allowed to price higher so you can recoup the costs of development, then [pharma] will get in."

Another key factor attracting big pharma to antibiotics: Competition with generic versions of first-to-market drugs is a problem for latecomers in many treatment areas, but drug resistant bacteria help sustain the antibiotic market.

"Once drugs go generic they've already made an impact on the presence of resistant strains," said Jeff Stein, president and CEO of Trius.

Given the life-threatening nature of some bacterial infections, doctors will use newer drugs even if most infections can be cleared with older, cheaper medications.

"For the most serious infections, you don't have a second chance. It's not like if your cholesterol is not lower this week you can try a new cholesterol-lowering drug. In this case, if you have pneumonia and it's resistant, you're not going to have a second chance," Fernandes said.

Risk and Reward

Clarity of FDA regulations could also help drive potential partners back into the space. Companies are expecting final FDA guidance on ABSSSI and community-acquired bacterial pneumonia (CABP) shortly, and draft guidances have already helped establish the endpoints required for a successful trial.

Clearing up regulatory ambiguities could help potential licensors avoid the fate of Advanced Life Science Holdings Inc., which got stuck between changing requirements for its antibiotic Restanza (cethromycin). The biotech recently suspended operations and terminated its staff after running out of cash. Arpida A/S's iclaprim and Replidyne Inc.'s faropenem also became casualties of regulatory uncertainty. (See BioWorld Insight, May 16, 2011.)

Several antibiotic drug developers previously waylaid by the FDA's shifting requirements have gotten their development programs back on track. In Phase III are Durata Therapeutics Inc.'s dalbavancin, Johnson & Johnson's Doribax (doripenem), The Medicines Co.'s oritavancin, and others.

Yet the regulatory minefield is not completely clear. Companies are still waiting on guidances for other indications, and Fernandes predicted many FDA decisions about clinical trial requirements will be "compound by compound."

Niche Licensing

Different pharmas are looking for different types of antibiotic products.

Bayer's license of torezolid, for instance, centered around the emerging markets. "The deal serves as an indicator of the growing importance of China and the Asia Pacific as a market for anti-infectives," said Trius' Stein.

Trius plans to out-license the EU rights to torezolid separately after Phase III data are reported in the first quarter of next year.

Optimer licensed the rights for its Clostridium difficile-associated diarrhea (CDAD) treatment Dificid in Europe, the Middle East and Africa to Astellas Pharma Inc. earlier this year. Astellas has a substantial presence in the anti-infective market, having also partnered with Theravance Inc. to market its antibiotic Vibativ (telavancin). (See BioWorld Today, Feb. 8, 2011.)

In the U.S., Optimer decided it could build out its own infrastructure. "The U.S. hospital market is very efficient. We can cover 70 percent of the CDAD cases with 100 sales reps," said John Prunty, CFO of Optimer.

But Prunty said Optimer wanted a little extra boost during the "critical time at the launch of the product," so the biotech signed up fellow anti-infective specialist Cubist Pharmaceuticals Inc. to help promote the drug. The two-year co-promotion agreement will allow the combined sales force to cover 90 percent of the CDAD cases.

Cempra has a macrolide called solithromycin to treat CABP, which is in a Phase II trial for the oral version and a Phase I trial for the I.V. formulation. The biotech is searching for partners now to push the drugs through the final phase of development.

If Cempra can't find a partner, Fernandes said the biotech's backup plan is to fund the program through an initial public offering (IPO) that it's working on simultaneously. Considering the current IPO market, however, the firm had best hope pharma's interest in the antibiotic space is indeed coming back.