SHANGHAI – Sciclone Pharmaceuticals Inc., a Foster City, Calif.-based company that brings specialty therapeutics to the China market, has secured a deal for China (including Hong Kong, Macau, Taiwan and Vietnam) with Theravance Biopharma Inc., for Vibativ (telavancin), a lipoglycopeptide antibiotic that addresses difficult-to-treat hospital-acquired infections and ventilator-assisted infections.

Around the world, there is an increase in multidrug-resistant gram-positive clinical pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) infections. The first line of attack in China is vancomycin, an antibiotic used to treat serious infections, initially isolated by Eli Lilly and Co. in the 1950s. But for those patients who develop a resistance to vancomycin in China, there are few to no alternatives. When that happens, it can lead to a serious medical emergency, although the prevalence of that condition in China is not well understood. “Vibativ is one of the few, if not the only, antibiotics proven to work against MRSA infection. Once vancomycin does not work any more . . . and there are cases of resistance in China, then Vibativ is the only drug that would be available,” said Friedhelm Blobel, president and CEO of Sciclone.

“Antibiotic resistance is an important situation in any country,” Blobel explained. “The population treated with vancomycin where it is not working any longer is a small segment, but a segment that has no alternatives.”

The smaller size of the population is perhaps reflected in the size of the deal. It totals a potential $6 million for Theravance in up-front and regulatory milestone payments. But that does not mean there is not potentially a much larger issue regarding antimicrobial resistance lurking around the corner.

“About 10 percent of the islets that we see in global studies have intermediate level of resistance to vancomycin,” Theravance CEO Rick Winningham told BioWorld Asia. “That means to us that globally the bugs are becoming less susceptible to vancomycin; thus, there is an opportunity to use Vibativ in those types of infections.”

Beyond the U.S., Vibativ has already secured deals for Europe, Canada, the Middle East, North Africa, Israel and Russia.

There is also the possibility for the addition of indications such as complicated skin and skin structure infections, and potentially bacteremia.

Vibativ is a bactericidal, once-daily, injectable. It has in vitro potency with a dual mechanism of action, inhibiting bacterial cell wall synthesis and disrupting bacterial cell membrane function. As a bactericidal, it is highly potent, Winningham said.

Sciclone is always on the hunt for good candidates to bring into its portfolio, and Vibativ’s ability to meet an unmet need in China is one important consideration in its favor. The other is that it has already been studied in 64 Chinese patients during a global phase III multicenter trial, the results of which led to Vibativ’s approval in the U.S.

Describing the clinical study experience in China, Winningham said, “The quality of the clinical work that was done in China was excellent; we worked with very good investigators.” He added that Theravance had good feedback from key opinion leaders about the potential to treat MRSA infections found in those hospitals.

POSSIBILITY FOR AN ACCELERATED PATHWAY

But China has strict requirements for imported drugs, the pathway that Vibativ would have to take before it would be available here.

A standard phase III study would require 200 to 300 Chinese patients, but given Vibativ’s importance and the data that already exist from Chinese patients, Sciclone hopes it will have a case for discussing the possibilities of an accelerated approval with local authorities that would permit forgoing a full-blown phase III study in favor of other options, such as a postmarketing study.

Yet the Chinese drug review system is notoriously understaffed and backlogged. It takes a minimum of 18 to 24 months of queuing before a clinical trial approval (CTA) application is even reviewed, let alone approved. (See BioWorld Today, April 1, 2015, and May 27, 2015.)

Blobel said he is “cautiously optimistic” the system will change for the better. In the meantime, he is prepared to go the full class III imported drug license route if an accelerated option is not possible.

“That is part of the playing ground if you are active in China,” he said. “It is not easy. We are convinced that differentiated drugs that have positive outcomes for patients will in the end be successful. If it takes longer, it might take longer for everybody.”

When the time comes for the drug to hit the market in China, Sciclone is planning on building synergies, given its sales force has extensive experience selling products like Zadaxin, an anti-infective product that generates some $100 million per year and has been approved in various countries, though not the U.S., for the treatment of hepatitis B, hepatitis C and certain cancers, and as a vaccine adjuvant.

“We know that space. It will certainly be a great addition to have Vibativ,” Blobel said.

“Sciclone is a company that understands the antibiotic market in China. They are a company that can work with us through the regulatory process and, of course, they currently market an anti-infective product,” added Theravance’s Winningham.

This is not Theravance’s initial foray in China; it has a long history in sourcing product. But when it came to finding a commercial partner, the company chose Sciclone, a firm that has significantly bolstered its anticorruption and compliance efforts since it found itself the target of an FCPA-related investigation that has yet to be concluded. It is that enhanced compliance culture that Blobel said makes Sciclone so attractive to listed companies coming into China.

In the meantime, Sciclone is prepared for the regulatory long haul.

Thankfully, it has some time on the clock for Vibativ’s intellectual property. The composition-of-matter patent in China does not expire until 2021,and the patent for the active ingredient that is specifically used in Vibativ does not expire until 2024. Blobel said he is counting on nine to 10 years of patent protection in China.

That might not be enough to stop the competition, however. There is, he has found, a generics maker that is going after the same active ingredient and has already filed for a CTA. But according to Blobel, without any data in patients, that firm has several hurdles to overcome to catch up to Vibativ.