Cellulite is the bane of women everywhere. Caused by the irregular tightening of connective fibers between the muscle and skin, cellulite mars the rump and thighs with uneven dimples and bulges, as if a layer of cottage cheese lies just below the skin. Cosmetic creams and lotions can make the skin look smoother by inducing swelling to mask the dimples, but there is no lasting solution.
In the parlance of drug discovery, that creates an unmet need and a potentially lucrative market, given the millions of dollars women spend on marginally effective remedies each year. Men are seldom affected by the cosmetic condition.
Sensing opportunity, San Diego-based Halozyme Therapeutics (NASDAQ: HALO) is working on a treatment that attacks cellulite at its source. The experimental remedy is an enzyme—recombinant human lysosomal proteinase—that digests collagen, the main protein of connective tissue.
When injected into a dimple, the enzyme “snips” the connective fibers tugging on the skin. Once the fibers are snipped, the dimple is released and the contour of the skin is smoother.
Although the enzyme isn’t ready for human tests, it has shown promise in animal studies, CFO Kurt Gustafson says. “We have the smoothest, most beautiful looking pigs you have ever seen,” he told me recently. One worry, of course, is that Halozyme’s enzyme will destroy more collagen than necessary and the skin will become flaccid as it loses its connectivity to underlying tissue. Halozyme addresses this problem by leveraging the enzyme’s inherent affinity for acidic environments.
Lysomal proteinase is normally found in lysosomes, digestive structures within cells. The pH inside lysosomes is 5-6, more acidic than the normal body pH of around 7. The enzyme is very sensitive to pH and is active only at the levels found in lysosomes.
Gustafson said the enzyme could be administered in the following manner: Before injecting the enzyme, a physician would increase the acidity of the target area by administering an anesthetic such as lidocaine, which has a pH of about 5. As the anesthetic wore off and the pH returned to normal, the enzyme would stop working-a process that takes about 20 minutes. At that point, the enzyme becomes an inactive protein in the body.
Gustafson said this procedure would allow the enzyme to target cellulite and minimize unwanted affects on other tissue. “By making it conditionally active, we can make it very safe,” he said.
Halozyme developed the enzyme, known as HTI-501, entirely in-house, so if it is successful in people-a big if at this point-the enzyme could be a very profitable product for the 12-year-old company.
Halozyme had expected to begin human tests of its enzyme in 2009 but the company delayed those studies in order to evaluate a second enzyme, matrix metalloproteinase 1, which also snips collagen but is activated by temperature. This enzyme would be injected at room temperature, its active state, and then would become deactivated by the higher temperature within the body.
In theory, “you could cool the area you are treating with an ice pack ahead of the injection and keep it cool for as long as you want the [enzyme] to degrade the collagen,” spokesman Robert Uhl tells me. He says the company is in the process of determining which enzyme looks best for various conditions, including cellulite, fibrosis and scarring, and which to move forward.
Gustafson said he couldn’t put date on when the company would begin human studies. “We are working to get the right formulation and have that put in place this year,” he said.
Clearly, the cellulite program is at an early stage compared to Halozyme’s programs in diabetes and cancer; important questions about safety and efficacy need to be answered. But if the cellulite shots work as well in people as they seem to in pigs, Halozyme may have a hit on its hands. This is a story we’ll be tracking.