The goal is to reformulate a drug and genuinely innovate at the same time.
When Linda Vahdat, MD, medical director of the Weill Cornell Breast Cancer Center, New York, heard about the FDA’s approval of Soltamox, a new liquid form of the breast cancer drug tamoxifen, she was thrilled. “I’m always looking for new products to treat my patients, but new formulations of old products are very useful, too,” says Vahdat. As many as 40% of adults have difficulty swallowing pills–a real handicap for women advised to take tamoxifen daily for years. “Soltamox really adds to the toolbox from a patient point of view.”
She wishes she’d had a similar liquid formulation to offer another patient. “I was dying to put her on oral chemotherapy with capecitabine, but she couldn’t swallow the pills, and there wasn’t another formula, so she’s now on an IV chemotherapy instead,” says Vahdat. “You’re always trying to expand your list of options for the patient, not shorten it.”
And that is what successful drug reformulations should be all about, experts say. “If you approach reformulation solely focused on patent protection, that’s not the right approach,” says Art Tipton, PhD, president and CEO of Brookwood Pharmaceuticals, Birmingham, Ala. “You need to be thinking about what you can do to improve the existing drug to make it a better product.”
With approval rates for new medications declining, research spending in 2005 reached an all-time high, but new chemical entity approvals were down 55%–many pharmaceutical companies are looking to the reformulation market as a smart, strategic way to balance their portfolios. A 2004 report on the US drug market from BCC Inc., projects that reformulations will grow from 62% of the market in 2003 to 79% in 2008.
Much of the discussion about reformulation is couched in the language of patent protection–when a drug is about to go off-patent, what can you do to protect the franchise? But successful reformulations take a far more strategic approach. “Extending the life of a brand should be driven by best principles and practices of good brand management. New formulations and new dosages should be about how they can add value to the end-user, for example, through added ease and convenience,” says Rebecca Robins, global marketing director for Interbrand Wood Healthcare, London, UK.
When thinking about reformulation strategies, the manufacturer should consider four players, Tipton says. “Is it valuable to the patient, valuable to the physician, valuable to the health providers–insurance companies and others–and is it valuable to the innovator of the drug? Ideally, you develop a reformulation strategy that works for all of those four.”
Improved delivery systems and options may be the biggest growth industry in reformulation. Moving beyond traditional categories, evolving possibilities include injectable
implants, inhalants, transdermal patches, and needleless reconstitution systems. “A classic candidate for new delivery systems is eye disease treatment,” Tipton says. “Systemically administered drugs don’t have a preference for getting to that site, so you need local injection, which is a lot more painful and stressful than an arm injection. So you want a system that will provide long durations of delivery–three months or longer–and will allow for very localized delivery.”
Elan uses its NanoCrystal technology to improve by as much as 600% the bioavailability of compounds that dissolve poorly in water. The drugs are still taken orally, but the difference in ease of use is dramatic, with lower required dosage, smaller and more convenient dosage forms, and faster rates of absorption.
One of the drugs they’ve reformulated this way is Bristol-Myers Squibb’s Megace, marketed for the treatment of wasting disease in people with AIDS. “The problem with the compound was that it came as a thick, viscous liquid. You had to swallow 20 ml, and you have to have eaten first,” says Breen. “We nanoized the compound and reduced the viscosity 16-fold, making it almost the same as water, and the patient just has to swallow a teaspoonful to get the same clinical effect.”
If you can’t reformulate the drug itself, sometimes you can reformulate the delivery system. “If liquid reformulation is not possible, the next best thing is to have the drug in a system that gives you the simplest method of reconstitution,” says Graham Reynolds, vice president of reconstitution and transfer systems for West Pharmaceutical Services, Lionville, Pa.
West’s solution: needleless reconstitution systems like MixJect and Clip’n’Ject. “These allow you to connect a syringe of a diluent to a vial with the lyophilized or dry powder drug, quickly and safely transferring between the vials and then transferring the reconstituted drug back into a syringe for administration,” says Reynolds.
About the Author
Shaw is a freelance writer based in Montclair, N.J.
This article was published in Drug Discovery & Development magazine: Vol. 10, No. 1, January, 2007, pp. 45-46.
Filed Under: Drug Discovery