Just days after the publication of promising data concerning its antibiotic drug candidate fidaxomicin, Optimer Pharmaceuticals Inc. has licensed the compound to Astellas Pharma Europe Ltd. to treat Clostridium difficile infections in Europe and additional territories.

Astellas paid Optimer $68 million upfront and has committed about $156 million in additional payments based on regulatory and commercial milestones if and when the drug is approved and marketed. In addition, Optimer will receive escalating royalty payments, which Optimer CEO Pedro Lichtinger pegged in the "high teens to low twenties" in terms of percentage during a Feb. 7 conference call.

The deal gives Astellas territorial rights to a drug that could receive U.S. approval by summertime. In a Feb. 7 research note, Robert W. Baird analyst Thomas J. Russo pegged U.S. sales of fidaxomicin at nearly $250 million annually by 2018, if approved.

The agreement comes during a period when antibiotic licensing or acquisition deals have ranged up to $500 million for worldwide rights (Also see "Antibiotic Firms Push Ahead With cSSSI Trials, Despite Lack Of FDA Guidance" - Pink Sheet, 23 November, 2009.). The terms are also right in line with an antiobiotic deal Astellas signed in 2005, when it paid Theravance Inc. $221 million, including $65 million upfront and $156 million in milestones, for worldwide rights for Vibativ (telavancin). The antibiotic for skin infections eventually reached the market after a series of delays (Also see "Theravance Gets To Market With Vibativ, But HAP Indication Could Be Pushed To 2010" - Pink Sheet, 14 September, 2009.).

C. difficile, a gram-positive bacterium that infects the gut and causes severe diarrhea, affects a growing number of patients in hospitals and other care facilities. Many infections occur after other antibiotics have been administered, affecting the balance of naturally occurring flora in the intestine and allowing C. diff to flourish.

Last week, the New England Journal of Medicine published data favorably comparing fidaxomicin to Vancocin (vancomycin), originally developed by Eli Lilly & Co. Inc. and licensed to ViroPharma Inc. in the U.S., the only drug currently approved to treat C. diff infections, or CDI. The new data, drawn from a North American Phase III trial, suggested comparable efficacy in treating the infections with substantially improved recurrence rates, relative to the standard-of-care drug. Some physicians also treat CDI with off-label prescriptions of metranidazole.

Orally administered fidaxomicin selectively inhibits a bacterial enzyme known as RNA polymerase, and appears to kill C. diff with relatively minimal interference to other bacteria that live in the gut. The drug is expected to improve on the observed relapse rate of 20% to 30% in patients treated with vancomycin or metranidazole, Optimer said.

In the conference call, Lichtinger said Optimer intends to position fidaxomicin as a first-line treatment for patients deemed to be at risk of recurrence, including the elderly, those taking other antibiotics concomitantly, those who have previously experienced a CDI episode, immune-compromised and renally-impaired patients. Those patients account for about 70% of CDI sufferers.

The company, which submitted a rolling New Drug Application in September 2010, has reason to believe that approval is coming soon. The FDA accepted its application and granted fidaxomicin a six-month priority review with a PDUFA date of May 30, potentially setting up the drug for approval and launch to market by summer 2011.

FDA recently said it is bringing the fidaxomicin application for review by its Anti-Infective Drugs Advisory Committee at its April 5 meeting. The agency commonly brings new molecular entities before advisory panels, and the fidaxomicin data so far haven't raised any issues that would trigger a committee review, so FDA is likely convening the meeting to better understand C. diff drug development. The NDA was based on two Phase III trials, which showed fidaxomicin to be non-inferior to vancomycin on the primary endpoint of clinical cure rate. It was also statistically superior to the older drug in reducing recurrences of C. diff infection and in global cure rate.

The data have been peer-reviewed; one of the trials was published in the Feb. 3 issue of the New England Journal of Medicine, although the data had been previously disclosed at medical meetings (Also see "Optimer Rides High After OPT-80 C. Diff Trial Success" - Pink Sheet, 12 November, 2008.). The rates of clinical cure in the modified intent-to-treat population were 88.2% on fidaxomicin (n=302) and 85.8% on vancomycin (n=327). The per-protocol analysis yielded rates of 92.1% and 89.8%, respectively. In the MITT population, 15.4% of patients taking fidaxomicin suffered a recurrence of their CDI, compared with 25.3% of the patients who took vancomycin; corresponding per-protocol rates were 13.3% and 24%.

A Hospitable Partner With Hospital Expertise

In the deal, Astellas will receive rights to develop and market fidaxomicin in Europe, selected countries in the Middle East and Africa, and the Commonwealth of Independent States. Optimer will retain rights in the U.S. and Asia, although it continues to explore partnership opportunities in Japan and China.

During its investor call, Optimer's Lichtinger said Astellas's existing presence in Europe and knowledge of the hospital market made it an ideal partner.. CFO John Prunty pointed to Astellas' experience marketing anti-infectious disease drugs in multiple geographies as well. Astellas currently markets Vibativ, the anti-fungal Mycamine (micafungin), and the fluoroquinolone antibiotic Avelox (moxifloxacin), the last via a co-promotional agreement in the UK with Bayer AG.

Prunty said Astellas' relevant sales team in Europe includes nearly 200 account managers. Astellas will shoulder all ongoing development, regulatory and commercialization costs in the territories it has licensed from Optimer.

Although Astellas is traditionally strong in Asia, Optimer has not tabbed it to partner in Japan or China yet. Lichtinger said the details of development programs and timelines for Asia have not yet been hammered out.

Optimer previously had a partnership deal for fidaxomicin with Par Pharmaceutical Companies Inc., which returned rights to Optimer in 2007. Optimer owes Par a 6.25% royalty on the newly partnered sales of the drug.

Financing a U.S. Launch, and Other Programs

Although Optimer's executives did not directly discuss how the partnership's proceeds would be earmarked, it's logical to assume some -if not all - of the proceeds will offset commercial expenses incurred if the drug gains approval mid-year. Optimer could hire anywhere between 60 and 125 staff to market the drug, at a cost of about $250,000 per representative, Lichtinger said. The company is still conducting market research and evaluating risk, he added.

The $68 million upfront payment alone is larger than Optimer's cash reserves of $58.7 million as of September 30, its most recent earnings report.

Publicly traded since 2007, Optimer conducted a secondary share offering in March 2010 that netted $51.5 million. Since that offering, priced at $11 per share, Optimer's share price dipped below $8 in the late summer before rebounding above $12 last month.

Optimer also has U.S. rights to Pruvel (prulifloxicin), another anti-diarrheal antibiotic it licensed from Nippon Shinyaku Co. Ltd. in 2004. Approved in Japan, Korea and multiple European countries to treat a variety of infections, Pruvel is a fluoroquinolone antibiotic that inhibits DNA replication. Optimer has Phase III data on Pruvel for infectious diarrhea, including traveler's diarrhea, and is working toward an NDA.

Elsewhere in its pipeline, Optimer has an oncology immunotherapy candidate intended to treat metastatic breast cancer, as well as an antibiotic candidate for community-acquired bacterial pneumonia and other macrolide and ketolide antibiotics thought to be effective streptococcus pneumoniae and other respiratory infections.

- Paul Bonanos ( p.bonanos@elsevier.com ). Mary Jo Laffler contributed to this story ( mlaffler@elsevier.com ).

Emboldened By Strong Data, Optimer Licenses Antibiotic Candidate To Astellas

More from Archive

More from Pink Sheet