When most people think of transdermal patches they think of the nicotine patch that became popular in the 1990s for chronic smokers struggling to kick the tobacco habit. More recently, patches have been marketed as a simple less-prone-to-forgetfulness means of contraception. And there are more on the way. Although no one is predicting that the traditional means of administering much needed drugs via teaspoonful or in pill form are going the way of the horseless carriage or the VCR, transdermal patches are certainly here to stay.
This is good news for Suresh Borsadia, founder and CEO of the Forrestal Village-based Abeille Pharmaceuticals. "There are a number of benefits to using transdermal patches," says Borsadia. He focuses on markets that include drugs used to treat oncology-related discomforts, diabetes and metabolic disorders. "We are looking to continue doing the work that is necessary in order to get them on the market as quickly and safely as possible."
Incorporated in Delaware in 2003, the company signed an agreement last month that grants it worldwide, exclusive rights to a chemical patented for use in transdermal applications. Borsadia would not disclose financial terms. Initially funded for $1 million, the firm has had two private rounds of financing and is in the midst of another round, due to be closed in September.
How its transdermal patches work: A medicated adhesive patch is placed on the skin to deliver a time-released dose of medication through the skin and into the bloodstream.
While the development of transdermal patches can be a slow and tedious process, with a number of daunting obstacles, Borsadia believes they represent the wave of the future. They are being developed for everything from birth control to anti-depressants to painkillers because they solve the traditional problem: What to do about overcoming the simple equation of "patient is ill, patient is given medicine, patient takes medicine, patient feels better, patient stops taking medicine, patient gets sicker."
The obvious advantage of dispensing drugs into the body via transdermal patch is that medication can be accurately administered for more than a day and as much as a week without the inevitable lapses by pill-taking patients.
But Borsadia cites other benefits. Many drugs tend to lose much of their usefulness when they are given to patients orally because portions biodegrade in the stomach or metabolize into the liver. By delivering these medications through the skin, it is possible to bypass these gastrointestinal effects, so a smaller amount of drug can be effective. This can help reduce side effects as well as lessen the frequency of dosage.
Abeille seeks to bridge the gap between big pharmaceuticals and drug delivery companies. Big pharmas often prefer to in-license finished products or products in late stages of development rather than partner for a technology-based product at an early stage of development. This reduces the pharma’s risk. But the drug delivery companies also want to limit their risk. They are more inclined to seek partners at an early stage of development.
Such opposite priorities have created an opportunity for companies such as Abeille, says Borsadia.
Currently Abeille is working on a patch for emesis (nausea and vomiting), and it recently completed a Phase I study under a U. S. Investigational New Drug Application for the transdermal anti-emetic product, AB-1001. After a preliminary review of the data, the company has begun activities for a Phase II study, which is expected to be completed this August.
Abeille’s plans call for initiating pivotal Phase III efficacy studies in the fall. "Most of the cancer drugs for people undergoing chemotherapy cause a lot of nausea and vomiting. This product is aimed at helping them avoid those negative effects," says Borsadia.
But as one might expect, Abeille operates in a very competitive environment. One rival, less than five miles away, is Borsadia’s former employer, Lavipharm, with a 50,000 square-foot R&D facility on Princeton-Hightstown Road. A firm with offices in Minneapolis and Basel, Switzerland, Antares Pharma, has just moved into Princeton Crossroads Corporate Center in Ewing (see sidebar, page 41). In East Windsor on Lake Drive, Core-Tech has a 10,000 square-foot manufacturing facility with 15 full-time and part-time consultants. (Core-Tech’s founder, Kirti Valia, is Borsadia’s former boss at Lavipharm, and is ready to file several new drug applications.) Another patch company, LTS, is in West Caldwell. Other rivals are working in Florida, California, Utah, and Ohio.
Borsadia believes his company has an edge because it is small, just two employees, and because its business model depends heavily on outsourcing. "We work with many different kinds of people in order to get things done," says Borsadia. "This allows us the flexibility to move products quickly through the development phase. We have not had to spend time on building an infrastructure because we are utilizing the capabilities that already exist." Instead of spending 18 months to build an infrastructure, he focuses directly on the product. "So now, in just a little over two years we have a product that is in Phase II and will be in Phase III by the end of the year."
But this is one technology that is not being outsourced to Asia. "For patches, there isn’t much know-how or capability in India," says Borsadia.
Borsadia is from Kujarat, in western India, where he attended Karnataka University, graduating in 1984. He spent six years working on his PhD at the University of Utah and started his professional career in 1991 at TheraTech Inc., (now Watson Pharmaceuticals) in Salt Lake City and Bertek Inc., (now Mylan Technologies, a division of Mylan Labs). Borsadia worked for seven years at Lavipharm, where he played a leading role in the company’s R&D, in-licensing, and out-licensing activities. He left Lavipharm in 2003 to start Abeille with Kalpana Patel, now an Abeille employee, and Vin Bhalani, co-founder of Sidmak Laboratories in East Hanover.
The name of the company came from the French word for honey-bee. "Like a honey-bee goes from flower to flower to collect nectar and create honey, we also seek to incorporate the best from various sources to create unique products," says Borsadia. "We also seek to inculcate a corporate culture that espouses hard work and a team spirit just like honey-bees."
Maryland-based GloboMax ICON is Abeille’s favored choice for clinical trials. A Florida firm manufactures its patch products, and a firm in Maryland manufactures another category of products, oral drugs for diabetes. Nicholas C. Maida on Princeton-Hightstown Road is the accountant, and the attorney is David Sorin of Morgan Lewis & Bockius at the Carnegie Center, with Arthur Jackson, formerly of Dechert, as the patent attorney.
A resident of Plainsboro, Borsadia has two children, a 12-year-old son and a daughter who begins kindergarten in the fall. His wife, to whom he has been married for 13 years, works at Bristol-Myers Squibb in New Brunswick.
While transdermal patches have been in existence for over two decades, their use has always been limited because many medications are just not conducive to its application. There are currently only about 10 drugs that have been commercialized for the transdermal patch, including those for smoking cessation, pain management, and hormone patches for women undergoing menopause and for contraception.
"It is difficult because the skin is designed to keep things from going into it," says Borsadia. "There is a limitation as to the size of the molecule that can go into the skin and the amount of a drug that can be delivered at one time. Typically, if the dose is more than two milligrams in a day, it becomes a challenge."
There are additional complications in developing transdermal patches. Over time, some drugs may cause an allergic reaction in patients. "A drug that is delivered through the skin may be seen as a foreign object by the body’s immune response system," says Borsadia. "The next time you give the drug, you will have the same sort of reaction you have with poison ivy. It is not what you want."
Despite the fact that drug delivery systems are now one of hottest areas of pharmaceutical research and development, the use of transdermal patches has also drawn its share of questions about safety and appropriateness. Several medications utilizing this method have been linked to a number of serious adverse reactions.
The Federal Drug Administration (FDA) has recently acknowledged a study that indicates women using a birth-control patch have an elevated risk of developing blood clots. In addition these women were said to have a significantly greater risk of stroke and death than woman who use other forms of oral contraceptives.
The nicotine patch is still one of the most popular forms of transdermal patch in use. Put on the market in 1992 as a prescription-only drug, it became available over-the-counter beginning in 1996. But it has been accused of having a number of problems associated with it, including disrupting sleep and causing vivid dreams in its users.
One of the most problematic transdermal patches has been the one containing the powerful painkiller fentanyl. In 2005, the FDA announced that it was investigating claims that the patch was responsible for some 120 deaths.
Designed to provide up to 72 hours of relief from severe chronic pain associated with such conditions as bone cancer, fentanyl is a dangerous drug and an overdose of the narcotic (100 times more potent than morphine) can induce a coma and shut down breathing. Improper administration of the drug or problems with the patch itself can have fatal consequences if either causes too rapid a release of the medication into the bloodstream.
But despite the challenges, transdermal patches are here to stay. They are convenient, ensure compliance with a drug regimen for people with problems remembering their medication schedule, and are particularly useful with drugs that require only low dosages.
This is something that Borsadia is counting on. Licensing the chemical will give his company its own platform on which to base future products. "Up to now," he says, "we have been creating our intellectual property on a product-by-product basis. Now we will have something that is proprietary, something that we can use for future products."
Abeille Pharmaceuticals Inc., 116 Village Boulevard, Princeton Forrestal Village, Suite 200, Princeton 08540; 609-951-2204; fax, 609-520-1702. Suresh Borsadia. www.abeillepharma.com
– Jack Florek
Implants, Alternative to Patches
Like transdermal patches, hydrogel implants offer automatic delivery, advantageous for those with chronic diseases, or for those with Alzheimer’s or arthritis or psychotic disorders who don’t remember to take their medication.
Hydrogels are a type of plastic – or polymer – with the advantages of both liquids and solids. They can function in a gel state but, like liquids, transport large molecules. They can have controlled thicknesses, and they can control distribution through filters and screens.
Like patches, hydrogel implants can be a silver lining for pharma companies with drugs that are about to go "off patent" and be sold as generic products. Put that drug in a hydrogel implant – using a material similar to that found in contact lenses – and not only does it represent a new revenue stream, but it has real advantages to the patient.
For instance, the previous treatment for prostate cancer involved painful monthly or quarterly injections in the stomach. In 2003 Valera Pharmaceuticals (formerly Hydro Med Sciences) began to market Vantas, a hydrogel polymer implant for prostate cancer.
Vantas, a 12-month hormone suppression therapy for advanced prostate cancer, contains the testosterone-reducing medication called histrelin. Vantas is a small, flexible cylinder that is placed under the skin of the upper inner arm. It remains in the arm to release histrelin continuously for a whole year. The histrelin reduces PSA – a prostate-specific antigen – a blood chemical associated with prostate cancer.
Valera is ready to begin Phase I/II clinical trials for a new narcotic addiction treatment that involves implanting a device under the skin of those addicted to pain-relieving drugs. The drug used, naltrexone, blocks euphoria-inducing chemicals produced by heroin and prescription pain killers such as morphine, hydrocodone, and oxycodone. It is approved for oral medication.
Valera has also filed a new drug application with the Food and Drug Administration to treat central precocious puberty, the premature development of secondary sexual characteristics in young children. Left untreated, the disorder can stunt a child’s growth.
The drug, Supprelin-LA, provides suppression of normal hormone production. The synthetic hormone used, histrelin, is approved for daily injection, but the new drug is a 12-month implant. The hydrogel technology dates back to the 1960s, when more than 100 scientists at Prague’s Academy of Sciences were laboring on polymer research projects. In the 1990s, so many Czech scientists moved to the Route 1 corridor, that it was dubbed "Hydrogel Valley."
– Barbara Fox
Valera Pharmaceuticals, 7 and 8 Clarke Drive, Cedar Brook Corporate Center, Cranbury 08512; 609-409-9010; fax, 609-409-1650. David Tierney, CEO. www.valerapharma.com
Transdermal Gel Move-In
Another transdermal drug delivery firm has come to Princeton. Antares Pharma CEO Jack E. Stover moved his six-person headquarters from suburban Philadelphia (Exton, Pennsylvania) to Princeton Crossroads Corporate Center during the second week in August.
A publicly held firm that trades on the American Stock Exchange, Antares Pharma develops drug delivery systems, such as transdermal systems, and injectable devices.
With R&D and manufacturing facilities in Minneapolis, Minnesota, and Basel, Switzerland, it has 29 patents and more than 100 applications pending in the U.S. and other countries.
With its partner firms, Antares is developing therapies for such conditions as diabetes, growth disorders, obesity, pain management, incontinence, female sexual dysfunction, and other hormonal problems.
In addition to its transdermal delivery system, it has an oral fast-melt technology, a disposable mini-needle injection device, and a reusable needle-free injection device. The needle-free injector systems are used in more than 30 countries, and Antares’ licensees use the transdermal system for an ibuprofen gel that is marketed in Europe.
The transdermal system employs a clear and cosmetically acceptable drug delivery gel. "Within a few minutes of application to the skin, an invisible depot is formed within the epidermis from which the drug is slowly absorbed into systemic circulation.
The gel contraceptive products developed under this agreement are expected to be generally safer than most oral contraceptives, convenient to use, and attractive to women who have problems taking oral contraceptives.
They will be under the complete control of the user and will be able to deliver multiple active ingredients simultaneously," according to company literature.
Stover, who lives in Bucks County, came to Antares in 2004. A graduate of Lehigh University, Class of 1975, he had been the partner in charge of the lifesciences practice of Coopers & Lybrand and CFO and CIO for Braun Medical.
In Princeton he was executive vice president of Gynetics, the privately held women’s healthcare company that developed the "morning after" pill. His most recent job was as executive vice president and CFO of Sicor Inc., the largest publicly-held vertically integrated specialty, injectable pharmaceutical firm. Sicor was recently sold to Teva Pharmaceuticals for more than $3.4 billion.
The CEO is Roger G. Harrison and James E. Hattersley is vice president of corporate development. Mark Bennison of Trillium Realty negotiated the lease, says Stephanie Baldwin, who is in charge of investor relations.
Baldwin cites reasons for the move: to be in the pharmaceutical corridor, to be close to Manhattan ("We go to New York at least a couple of times a month"), and to be closer to Newark Airport.
Says Stover: "We are an international company, and when visitors came in through Newark, it was such a journey to Exton."
– Barbara Fox
Antares Pharma Inc. (AIS), 250 Phillips Boulevard, Princeton Crossroads Corporate Center, Suite 290, Ewing 0868; 609-359-3020; fax, 609-359-3015. Jack E. Stover, president & CEO. www.antarespharma.com