Novel strategies for drug delivery, as well as new twists on old approaches were among the topics of discussion at the annual Roth Capital Partners Conference, recently held in Dana Point, CA.
Citing drivers such as bioterrorism, natural disasters, and global travel, Una Ryan, Ph.D., president and CEO of Avant Immunotherapeutics (www.avantimmune.com), explained how her company’s needle-free oral vaccines are providing answers in a rapidly growing, multibillion-dollar market, especially in the area of public health threats.
Avant’s single-dose, oral typhoid fever vaccine candidate, Ty800, is currently in clinical trials sponsored by the NIH. The vaccine was developed using genetic techniques that delete specific genes known to be essential to the virulence of Salmonella typhi, the cause of typhoid fever, according to Dr. Ryan.
Using fermentation, Avant engineers organisms that are immunogenic but not toxic and develops a “Trojan horse“ into which antigens can be inserted.
The company also has conducted clinical trials on its single-dose, oral cholera vaccine, CholeraGarde.
Avant has partnered with GlaxoSmithKline (GSK; www.gsk.com) on its Rotarix two-dose oral vaccine that protects against rotavirus diarrhea. Approved in 25 countries, Rotarix is the first human rotavirus vaccine derived from a human virus strain. It can be co-administered with all major infant vaccines, including oral polio vaccine. AVANT in-licensed the vaccine to GSK Biologicals in 1997.
Also involved in drug delivery programs, especially those geared toward large molecule drugs, is Bentley Pharmaceuticals (www.bentleypharm.com), which recently signed a product licensing agreement with Biocon (www.biocon.com) for Bentley’s intranasal spray formulation for administering insulin. The intranasal format enhances permeability through membranes while being nontoxic, nonreactive, and nonirritating, notes John Sedor, president of Bentley. The company’s product, for which Phase II and III studies are planned, offers bioavailability of 15% with rapid onset of action, he said.
Bentley is also counting on the favorable demographics and market dynamics of an aging population to develop specialty generics. “Because public and private payers are pressuring the health care companies, generic utilization is promising,“ Sedor said. “In addition, 72 drugs with $67 billion in sales are losing their patent protection between now and 2009.“
Another company involved in “generic products with sustainable profitability“ is Taro Pharmaceutical Industries (www.taro.com),according to Kevin Connelly, CFO. The company, which was established in 1950 in Haifa, Israel, expanded into the U.S. in the 1990s and focuses on topical products for dermatology, pediatric, and neurological applications.
Taro Pharmaceuticals U.S.A. markets Ovide, a prescription product for the control of head lice. Future plans include a Phase III study for a new formulation that has a shorter application time and is easier to use, thus potentially improving compliance. Taro also has received FDA approval for topical preparations for impetigo, inflammatory skin conditions, and fungal conditions, as well as tentative approval for its ANDA for capsules used to treat epilepsy and post-therapeutic neuralgia.
Diaper dermatitis affects 8 million infants in the U.S., and only one product, Vusion from Barrier Therapeutics (www.barriertherapeutics.com), has FDA approval to treat it when it is complicated by an infection of the yeast Candida, says Geert Cauwenbergh, chairman and CEO. The steroid-free formulation contains the active ingredient miconazole nitrate at a concentration of 0.25% to treat the fungal infection.
Barrier also filed an NDA for another drug, Sebazole, a nonsteroidal, once-a-day treatment for seborrheic dermatitis, which affects between 8.5 and 14.3 million people in the U.S. Sebazole requires two weeks of treatment with once daily application to be effective, according to Cauwenbergh.
Other Barrier products under development include treatments for acne, psoriasis, and fungal infections. The company markets Solage, a topical solution for the treatment of solar lentigines, in the U.S. and Canada and distributes Vaniqa, a cream for the treatment of unwanted hair and Denvair for the treatment of cold sores in Canada.
CollaGenex Pharmaceuticals(www.collagenex.com) filed an NDA for Oracea, a systemic compound for the treatment of rosacea. In addition, it is in Phase II trials to evaluate Incyclinide for the treatment of acne.
CollaGenex is evaluating various chemically modified tetracyclines that inhibit multiple proteases and cytokines. It also acquired the Restoraderm technology, a proprietary topical foam dermal drug delivery system.
Focusing on dermatology since 2001, Connetics (www.connetics.com) was founded in 1993 as a spin-off with development-stage products from Genentech (www.gene.com) for connective tissue diseases.
Currently, the company is also marketing pediatric products for acne and allergy. FDA-approved products include Luxiq foam for the treatment of corticosteroid-responsive scalp dermatoses; 0.12%, Olux foam for short-term topical treatment of inflammatory and pruritic manifestations of corticosteroid-responsive scalp dermatoses and short-term topical treatment of mild-to-moderate plaque-type psoriasis of non-scalp regions; 0.05%, Evoclin foam, a topical clindamycin foam for the treatment of acne vulgaris; and 1%, Soriatane, 10 mg and 25 mg capsules, a once-a-day oral medication for initial and maintenance treatment of severe psoriasis in adults.
Connetics created an in-house Center for Skin Biology to connect the scientific understanding of skin diseases with better treatment options. Currently, the company offers a patented aerosol foam delivery system, VersaFoam, a thermolabile, quickly evaporating foam, which facilitates the movement of a medication across the skin’s protective barrier, explains a company spokesperson.
Connetics is developing Liquipatch, a patented, multi-polymer gel-matrix delivery system that applies to the skin like a normal gel and dries to form a thin, invisible, water-resistant film that enables a controlled release of the active agent.
Small Molecule Oncologicals
Array BioPharma (www.arraybiopharma.com) has a drug development pipeline centered on the treatment of cancer and inflammatory disease and includes clinical candidates designed to regulate therapeutically important targets, according to its CEO, Robert E. Conway.
Using the Array Discovery Platform, the company’s integrated suite of drug discovery technologies, Array has identified multiple drug candidates in its own programs and in collaborations with other drug companies. Its research has resulted in out-licensing three programs to AstraZeneca (www.astrazeneca.com) and Genentech.
Another small molecule drug firm, ArQule (www.arqule.com), is engaged in R&D of cancer therapeutics. It researches and develops cancer drugs with reduced toxicities, as compared to conventional cancer chemotherapeutics, explained a company spokesperson.
ArQule’s approach is intended to restore and activate cellular checkpoints through the use of small molecule drugs. Its Activated Checkpoint TherapySM platform is selective for cancer cells.
By activating checkpoint functions without damaging DNA, drug candidates based on the ACT platform are designed to cause the selective demise of cancer cells, while sparing normal cells. The objective is to create a less toxic class of drugs that will be more effective across multiple cancer types than chemotherapy.
Hythiam’s (www.hythiam.com) Prometa protocols are intended to normalize malformed GABA receptors in the brain, putting them back into equilibrium without causing anxiety.
The treatment, which is administered orally and intravenously, results in greater compliance, said Sanjay Sabnani, vp of strategic development.
Somaxon Pharmaceuticals (www.somaxon.com) has in-licensed three product candidates: Silenor (doxepin hydrochloride), which is in Phase III trials for the treatment of insomnia; nalmefene hydrochloride, currently in a Phase II/III for the treatment of pathological gambling; and a Phase II trial for smoking cessation.