A few months ago, Pfizer (NYSE:PFE) announced that its CDK inhibitor palbociclib (Ibrance) received FDA approval for the treatment of breast cancer, when given in combination with fulvestrant, an estrogen receptor modulator. The expanded label now provides a new treatment option for a wider range of women.
The long story short: women with hormone-positive breast cancer have a generally very good prognosis with surgery and antihormone therapy. In fact, many will be able to live their normal lives and will not die of cancer. However, a certain portion of patients will develop metastatic disease, which is considered incurable. Moreover, the outlook for these patients is quite grim, which necessitates further research into effective treatment options in the metastatic setting.
Ibrance was developed to capitalize on the tendency for tumors to rev up their growth to out-of-control levels. Cancer cells can accomplish this by dysregulating cell cycle control, such as that controlled by cyclin-dependent kinases (CDKs). By blocking certain CDKs, Ibrance is able to stall proliferation in tumor cells, and that's what led to its exploration as a therapy for cancer.
Original Approval: Confirmed by PALOMA-2
What's the difference in the expanded label? Originally, Ibrance was indicated for post-menopausal women in combination with letrozole, an aromatase inhibitor. Their tumor had to be hormone receptor positive and HER2 negative.
This approval was based on the results of PALOMA-1, a randomized Phase 2 trial that led to an accelerated regulatory pathway for women with breast cancer. However, it is important to note that accelerated approval is based on surrogate endpoints. These are clinical trial endpoints designed to predict what the overall benefit for patients will be.
Addition of Ibrance to letrozole significantly improved progression-free survival in the PALOMA-1 study, leading to its accelerated approval. This past week, Pfizer announced confirmatory results from PALOMA-2. The full findings are expected to be presented at ASCO this May/June. However, it can be reasonably assumed that the researchers in this study have identified an overall survival benefit for Ibrance. And Pfizer expects to use these data to convert the accelerated approval into a full approval in combination with letrozole.
Now, the investor is likely asking himself or herself "Why should I care about a confirmatory trial?" Recall, in order for the drug to be successful in the marketplace, it must be not only approved, but also accepted by clinicians who will prescribe it. In the case of Ibrance, Pfizer is operating in a crowded field of therapeutic options, and clinicians often struggle to remain updated with the latest findings. When a trial comes along to confirm the benefit of the drug, then its use starts to become best practice, and it will be prescribed more often in the right patients.
New Indication for Ibrance
Speaking of the "right patients," Pfizer has also recently expanded the potential beneficiaries of Ibrance. In PALOMA-3, Ibrance was combined with fulvestrant, an anti-estrogen agent with a different mechanism of action.
One major difference in the PALOMA-3 and prior PALOMA studies was the population receiving therapy. In PALOMA-3, women were enrolled regardless of their menopausal status. If she had hormone receptor-positive disease, she was eligible. And while premenopausal women are not as numerous among breast cancer victims, women under the age of 50 make up nearly 20% of all new invasive breast cancer diagnoses. So this expansion into premenopausal status represents a significant widening of the potential patient base for Ibrance.
What were the results of PALOMA-3? Addition of Ibrance to fulvestrant improved progression-free survival from 4.6 months to 9.5 months. The response rate to therapy was also more than doubled. These results are impressive considering the women in question had failed prior hormone-based therapy. On the basis of this study, Ibrance has now been approved for management of hormone-positive breast cancer, regardless of menopausal status, in combination with fulvestrant for women who failed prior hormonal therapy.
Future Direction for Ibrance
So what's the bottom line for Pfizer? In 2015, the company saw total revenue just north of $700 million worldwide for this agent. Pfizer has been rapidly expanding its use into other countries, and it is anticipated that worldwide revenues will continue to expand, reaching above $2 billion by 2021.
Other clinical studies are testing the benefit of Ibrance in different clinical settings, such as early breast cancer, as well as combinations with different anti-hormone therapies like exemestane. Of course, while Ibrance is the first CDK inhibitor to reach marketing approval for breast cancer, there is competition. Eli Lilly's (NYSE:LLY) abemaciclib was recently granted breakthrough therapy designation for heavily pretreated patients. This signals potential crowding in this emerging targeted therapy market.
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