Competitive combination strategies
Pharmaceutical companies have leveraged combination products in a variety of ways to gain competitive advantages and enhance
Roche/Her2+ combination products. Roche has been masterful in designing and executing winning drug combination strategies as exemplified by its fixed-dosed,
free, and drug-conjugate combinations targeting patients with HER2+ breast cancer. For over a decade, Roche's monoclonal antibody
Herceptin combined with chemotherapy has been the mainstay of treatment for HER2+ metastatic breast cancer (mBC). Last year,
the company launched Perjeta, a first-in-class HER dimerization inhibitor to be used in combination with Herceptin for mBC.
Early this year, Roche launched Kadcyla, the first antibody-drug conjugate (ADC) for the treatment of HER2+ mBC. Roche is
positioning Kadcyla—which contains Herceptin—to eventually replace Herceptin as a first-line mBC agent in combination with
Perjeta and become the monotherapy of choice for second-line treatment of mBC. "Kadcyla is an antibody-drug conjugate representing
a completely new way to treat HER2-positive metastatic breast cancer, and it helped people in the EMILIA study live nearly
six months longer," said Hal Barron, MD, Roche's chief medical officer and head, global product development. "We currently
have more than 25 antibody-drug conjugates in our pipeline and hope this promising approach will help us deliver more medicines
to fight other cancers in the future."
Gilead Sciences/HCV combinations. Gilead is using a similar drug combination strategy to win in the HCV infection space as it did in HIV. Data presented in
March demonstrated that a triple regimen of the HCV sofosbuvir, ledipasvir, and ribavirin produced a 100 percent response
rate after 12 treatment weeks for HCV genotype 1 patients. In June, the FDA granted priority review for Gilead Sciences new
drug application for sofosbuvir, a once-daily oral nucleotide analogue inhibitor for the treatment of HCV infection in combination
with ribavirin (RBV) as an all-oral therapy for HCV-infected patients with genotypes 2 and 3 and in combination with ribovarin
and pegylated interferon for treatment-naïve patients with genotypes 1, 4, 5, and 6. Gilead is developing a sofosbuvir-ledipasvir
coformulation that is being tested with and without ribavirin. FactSet Research Systems estimates that annual sales of sofosbuvir
and its combinations will exceed $6 billion and become the company's biggest selling product by 2017.
Teva/combination strategy. Teva Pharmaceuticals, the world's largest generic manufacturer, has announced that combination drugs and products represent
an integral part of its new competitive strategy. Teva is pursuing "new therapeutic entities," new formulations or combinations
of older drugs, which would leverage Teva's competitive advantages in generics, innovative specialty CNS drugs, and product
formulation. For instance, Teva recently acquired Alexza Pharmaceuticals and its Staccato aerosol delivery system to serve
as the platform for many new product combinations using already-approved drugs. In January, the FDA approved Alexza's first
product Adasuve, which combines the nearly 40-year-old anti-psychotic drug loxapine with the company's new inhalation delivery
Scientific, clinical, regulatory, and commercial factors will continue to stimulate the development and utilization of drug
combinations and shape the competitive landscape. Progressive companies will seek to preempt rivals by evaluating and developing
their in-house drug candidates, identifying external drug and product combinations and partners, and by preparing insightful
competitive strategies to win the drug combination competition.
Stan Bernard, MD, MBA, is President of Bernard Associates, LLC, a global pharmaceutical industry competition consulting firm, and a member of Pharm Exec's Editorial Advisory Board. He can be reached at SBernardMD@BernardAssociatesLLC.com