To enhance the safety and efficacy profile of its probable future blockbuster cancer drug, "Palbociclib," Pfizer (PFE) collaborated with GlaxoSmithKline (GSK). The company will evaluate Palbociclib in combination with GlaxoSmithKline's MEK inhibitor "Mekinist," also known as "Trametinib," under Phase I and Phase II trials, for treating patients suffering with advanced or metastatic melanoma. These trials are designed to test the effects of this combination on tumor biomarkers. It will also demonstrate the safety profile and anti-cancer activity in patients with BRAFV600, which is responsible for developing cancerous cells, including the NRAS mutations.
With its previous experience of developing BRAF inhibitor, "Tafinlar," or "dabrafenib," which was approved by the FDA in May 2013, GlaxoSmithKline will be responsible for conducting this combinational study.
Mekinist is one of the four drugs that was approved by the FDA in the last couple of years for treating melanoma patients. This combinational therapy of Mekinist and Palbociclib has to compete with present melanoma drugs like Bristol-Myers Squibb's (BMY) melanoma drug "Yervoy" and another BRAF-targeting drug, "Zelboraf," which is co-developed by Daiichi Sankyo (OTCPK:DSKYF) and Roche holding (OTCQX:RHHBY). Both Yervoy and Zelboraf are on their way to achieve the blockbuster status.
I think this combinational therapy will be successful not just because of the two big brand names but because of its superior efficacy in treating the current indications and the positive results from their previous combinations.
Palbociclib's efficacy in previous combinations
Palbociclib is an experimental drug that mainly targets advance and metastatic breast cancer and it is currently in its Phase III trial for treating women suffering from advanced breast cancer. Palbociclib also helps block two enzymes known as cyclin dependent kinases, or CDK 4 and CDK 6. CDK is a protein that regulates the cell growth cycle.
Pfizer, in an early stage study, evaluated the efficacy and safety of Palbociclib in combination with Novartis's (NVS) metastatic breast cancer drug, "Femara." In this study, Palbociclib achieved the primary endpoint related to progression-free survival, or PFS, of 26.1 months compared to 7.5 months for Femara alone, and Palbociclib alone was able to attain the PFS of 18 months in this Phase II trial. Looking at these superior results, Pfizer initiated the Phase III trial in the same combination as the first-line treatment of estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer in post-menopausal women.
After evaluating the efficacy and safety profile of Palbociclib in the trial phases, the FDA granted the breakthrough designation for the treatment of breast cancer patients. The breakthrough treatment is intended to expedite the development and review of drugs that can be used alone or in combination to treat fatal diseases.
Pfizer, in collaboration with AstraZeneca (AZN), also initiated the Phase III trial of Palbociclib in combination with AstraZeneca's "fulvestrant." In this trial, women suffering with HER2 negative metastatic breast-cancer, whose disease has progressed after the previous endocrine therapy, will be enrolled. The company will evaluate the efficacy or superiority of this combinational therapy compared to fulvestrant alone in prolonging PFS in these women.
Probable opportunity for Palbociclib
According to the American Cancer Society, breast cancer is the most common tumor found in women. It is expected that almost 230,000 women in the U.S. will be diagnosed with breast cancer this year and more than 39,900 will die from it. This number is expected to grow in the future.
Palbociclib, with its safety and efficacy demonstrated in the trial phases, enhances the tolerability of cells to limit the development of tumor cells. If Palbociclib is able to report higher efficacy in its late-stage trial, which is the most important requirement in treating early stage breast cancer, then it has a strong chance of deepening its foothold in the breast cancer drug market. Further, according to the company, it is expected to extend the Palbociclib drug to benefit around 200,000 women suffering from metastatic breast cancer. If Palbociclib is able to receive approval for treating multiple cancer indications, then it is expected to enhance its footprint in the cancer drugs market, which is estimated to reach around $84 billion by 2017.
Pfizer is optimistic on the success of this drug in late-stage studies and some of the pharmaceutical analysts expect Palbociclib will be the next blockbuster drug for the company. Palbociclib may generate revenue of $5 billion for the company during its peak sales period and around $3 billion revenue from treating metastatic cancer alone.
On the other hand, GlaxoSmithKline's new melanoma drugs "Tafinlar" and "Mekinist" are expected to generate strong competition for Bristol-Myers Squibb's Yervoy and Roche's Zelboraf. The company is evaluating the combinational therapy of both its drugs to treat adults with unresectable or metastatic melanoma, who also have BRAF V600E or BRAF V600K mutations. In September 2013, the FDA granted the priority review status for this combination of "Tafinlar" and "Mekinist" for treating metastatic melanoma.
GlaxoSmithKline has also filed an application for this combinational therapy and Mekinist as monotherapy, with the European regulatory earlier this year and both are under review. The FDA approved both drugs earlier this year and their combination is expected for review in early January 2014. Some of the analysts have predicted that this combination could surpass Zelboraf and claim the second position in the market behind Yervoy.
Novartis as its strong competitor
Novartis is developing its new type of breast-cancer drug, "LEE011," which is used for the same indications as Palbociclib. The company is expected to initiate the late-stage Phase III trials of LEE011 next month by enrolling around 500 women. In Phase III trial, Novartis will evaluate the efficacy of LEE-011 in combination with Femara (letrozole) in postmenopausal women undergoing treatment for advanced or metastatic breast cancer. It is expected that this trial will complete in November 2016.
Further, in another ongoing Phase I study on pediatric cancers, LEE011 is being tested as a single agent in neuroblastoma and malignant rhabdoid tumors. Novartis has identified unique indications and combinations of drugs with LEE011, in which LEE011 has demonstrated superior results in anti-tumor activities. With this initiative by Novartis, Pfizer could face the competition sooner than its expectation. However, LEE011 sales are not yet estimated as the company hasn't revealed the mid-stage clinical trial data for LEE011.
Pfizer's oncology segment showed strong sales growth of 24% to $407 million in the third quarter of 2013, and by looking at its performance and its continuous effects in developing more efficient cancer-fighting drugs, I expect it will perform even stronger in the coming quarters also. The superior efficacy and safety profile of Palbociclib will help it receive regulatory approval comfortably. If approved, it is expected to generate a multi-billion opportunity for the company. This will be an optimistic sign for investors after the approval of Palbociclib as a monotherapy or its combinational therapies, Pfizer will have enough time to deepen its foothold in this drug market before its competitors launch their drugs.