Issue Date: March 10, 2008
Keeping Baby Home
WHEREAS BIG drug companies have the financial mettle to support losing molecules in their search for a winner, most biotech firms do not have that luxury. Clinical trials are expensive, and small biotechs often can't afford to fund multiple products through the later stages of development.
As a result, many small companies have no choice but to throw the bulk of their resources behind that one drug they think can make it to market. When putting all your eggs in one basket, as Ella Fitzgerald and Louis Armstrong sang, "Lord help you if that baby don't come through."
With such high stakes, every decision along the drug development path, from choosing a candidate to designing trials to finding the best suppliers, can be make or break. For Anthera Pharmaceuticals, a privately held biopharmaceutical company based in San Mateo, Calif., it was therefore critical to find the right manufacturing partner for its lead drug candidate, varespladib. The company didn't have to look far; it turned to Albemarle's fine chemicals unit to help get its baby to market.
Anthera has three promising products in the pipeline. But varespladib, a pill for treating atherosclerosis, is its most important asset. Heart disease affects a vast patient population, and the drug could have blockbuster sales if it makes it to market.
Eli Lilly & Co. and the Japanese firm Shionogi discovered varespladib. The drug blocks a calcium-dependent enzyme called secretory phospholipase A2 (sPLA2), which plays a role in the inflammatory cascade. Lilly considered the drug for indications such as sepsis, rheumatoid arthritis, and ulcerative colitis but halted development in 2000 after weak results in Phase II clinical trials for those diseases.
Anthera's management, made up of former employees of Lilly and Peninsula Pharmaceuticals, which had a partnership with Shionogi, caught wind of the outlicensing opportunity. They thought the drug could be useful in treating atherosclerosis, a disease in which cholesterol-based plaque builds up on the lining of arteries.
According to Anthera, sPLA2 remodels both the "good" and "bad" cholesterol carrying lipoproteins. This results in small, dense LDL particles that carry the bad cholesterol and renders the good HDL particles less effective at scavenging cholesterol. That same process of lipoprotein modification also causes more cholesterol-carrying LDL particles to glom onto the inside of vessel walls as part of atherosclerotic plaques. Anthera believes varespladib could find new life as an agent that lowers plaque-causing cholesterol because it blocks sPLA2.
Varespladib would not replace statins, which dominate the lipid-lowering category of drugs; rather, it would be used in combination with them, says Debra Odink, Anthera's vice president of pharmaceutical research and development. Given the size of the cholesterol-lowering market and that no other company is developing oral drugs that inhibit sPLA2, Anthera believes the drug could be a billion-dollar seller.
ALL THIS meant it was critical to find the right manufacturing partner, one that would deliver a quality product on time. Anthera already had solid knowledge of the molecule's synthesis based on Lilly's experience. Lilly had sold roughly a ton of the active pharmaceutical ingredient (API) to Anthera as part of its licensing pact. That quantity got Anthera through Phase II trials.
The biotech's aggressive timelines presented challenges for prospective manufacturing partners. The company's concern out of the gate was finding a manufacturer that could both demonstrate the process chemistry and build a very strong analytical package, says Scott Chadwick, Anthera's director of chemical and pharmaceutical operations.
Anthera enlisted the Syracuse, N.Y.-based consulting group Rondaxe Pharma to help find a contract manufacturer. In addition to demanding a tight timetable, Anthera sought a manufacturer with "top-notch talent" and the capacity to make lab-scale and commercial quantities. And preferably one based in the U.S.
The matchmaker solicited bids from several firms and returned to Anthera with a handful of options. Albemarle was the best fit. Anthera hired the company to improve the production process for the API and then to manufacture the API to current Good Manufacturing Practice standards for Phase III trials. Their agreement also includes an option for future commercial-scale manufacturing of the drug. That option would be a boon for Albemarle if the market for the product turns out to be as vast as Anthera is predicting.
Anthera says it picked Albemarle because, in addition to meeting its basic requirements, a few bonuses made the manufacturer stand out. One attractive feature, Chadwick says, is an internal program at Albemarle that trains manufacturing engineers across multiple disciplines. Engineers with broad experience may "come up with ideas that a pharmaceutical engineer might not think of," he says.
Furthermore, as a broad-expertise manufacturer rather than a contract manufacturing specialist, Albemarle was financially stable and able to weather a downturn in any one of its businesses.
Albemarle was also cost competitive. "We certainly could have saved a few nickels by going offshore," Chadwick acknowledges. "But I'm confident we would not be where we are today" if Anthera had taken that route. For a small biotech firm with a project this critical to its future, the ability to make frequent visits to its supplier is critical, he says. For future manufacturing projects, he adds, Anthera will consider offshore suppliers.
FOR ITS PART, Albemarle is in tune with how vital one product can be to a small biotech. "These companies may have only one or two products, so each one is life or death," says David Clary, vice president of fine chemistry services. Biotech firms don't want to worry that their project will be pushed down a contractor's to-do list if an opportunity with a big pharma company comes along. "They want to know that they're important to us and that we're not just going to produce the material but give them the services they need."
To that end, Albemarle's fine chemicals services unit has recently started offering customers a project manager, the point person who can quickly handle all inquiries from a partner. "We always had project leaders internally, but now they are more visible to the customer," says Matthew Hancock, the project manager handling the Anthera contract.
The strategy is working so far. To date, Albemarle has hit all of Anthera's deadlines, and the companies have even started moving up targets. After initial work at its process development center in Baton Rouge, La., Albemarle shifted the project to its South Haven, Mich., plant for large-scale manufacturing. "We went from lab-scale quantities, around 25 g, to 125 kg in six months," Chadwick notes. "It was a tough challenge, but they put the resources behind it to get it done."
Anthera recently met with the Food & Drug Administration to discuss the results of its Phase II trials and expects to start enrolling patients for Phase III studies this quarter. If everything goes according to plan, Anthera will be on track to submit a New Drug Application to FDA by the second quarter of 2010.
Under an optimistic timeline, varespladib could gain approval in 2011, otherwise known as the year that Pfizer's cholesterol-lowering drug Lipitor goes off patent. It's just a few short years before Anthera executives find out whether their baby has come through.
- Chemical & Engineering News
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