ASCO 2011: the swirling maelstrom of news, views and innovation
Ian Hicks, Gordon Gochenauer, Thierry Devevey and Stephanie Hawthorne
The American Society of Clinical Oncology (ASCO) conference is regarded by many as the premier event on the oncology calendar. With some 30,000 attendees representing a plethora of professional functions and capabilities, one might wonder, “What makes ASCO so important?” Simply thinking through some of the rationale is confusing enough, as one considers the multiplicity of topics, be they scientific advancements, biomarkers, personalized medicine, clinical trial results and announcements, patient information, or cost or market access issues — and this is only the beginning of the areas covered. Consider then the different interests that are present in the form of practicing oncologists, hematologists, surgeons, radiologists, researchers, corporate R&,D, marketers and consultants, agencies, market researchers, news media, analysts…the list goes on. As for the economics of the meeting, when one considers all of the investments, could this almost equate to the annual budget of a small country?
Impact of news releases during ASCO greatly affects emerging companies
Larger companies might envisage ASCO as important but as only one route for information dissemination, whereas smaller, emerging companies might see the meeting as the vital venue for an announcement. This seems to be exemplified by the comment made by Spiro Rombotis, CEO of Cyclacel Pharmaceuticals Inc.: “We live or die by the ASCO timetable,” (quoted by Arlene Weintraub in Xconomy, May 31, 2011). On June 6, interim results from an ongoing multicenter Phase I / II clinical trial of Cyclacel’s sapacitabine were reported in a poster session. “Based on the interim results reported at ASCO, the sequential administration of sapacitabine (CYC682) and decitabine (Dacogen®, Eisai) appears safe and active in elderly patients with newly diagnosed AML [acute myelogenous leukemia],” said Hagop Kantarjian, MD, Chairman and Professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center and principal investigator for the study (Cyclacel press release, June 6, 2011).
“These announcements at ASCO quite often have a huge effect on stock prices, particularly those of emerging companies.”
These announcements at ASCO quite often have a huge effect on stock prices, particularly those of emerging companies. One example of a small company benefitting from positive news at ASCO is Ariad Pharmaceuticals, whose investigational mTOR inhibitor, oral ridaforolimus (AP23573), is being studied in patients with metastatic soft tissue or osteosarcomas. The positive results of the Phase III SUCCEED trial were presented in an oral abstract session at ASCO on June 6, accompanied by a combined press release by Merck and Ariad (by Meg Tirrell – June 6, 2011, 1:30 PM PT). On this news, Ariad’s share price jumped more than 18% over three days. See Exhibit 1 below.
The Ariad example is positive, however, in some cases, analysts and stockholders may not always see results in the same light. Examples of other company share price changes as a potential consequence of ASCO are provided below. (Note: We have not entered into any detailed analysis as to why a stock price may have either risen or fallen, and any link with presentations at the ASCO meeting may be coincidental):
Company economics aside, ASCO is possibly the single most important event each year for the field of oncology for multiple other reasons, not the least important of which is clinical advances. How does it all come together, and what is the primary message? The President of ASCO 2010-2011, George W. Sledge, MD, possibly said it best with his selection of the theme “Patients. Pathways. Progress.” This theme was well-represented at ASCO 2011.
“ASCO is possibly the single most important event each year for the field of oncology for multiple other reasons, not the least important of which is clinical advances.”
Between the Plenary presentations of pivotal trials for Yervoy® (ipilimumab, Bristol-Myers Squibb) and vemurafenib (Roche/Daiichi-Sankyo), outgoing ASCO President Sledge referred to 2011 as the “year of melanoma.” In a disease where no drug has been approved in over 20 years, 2011 was witness to two successful Phase III trials in treatment-naïve metastatic melanoma patients. Yervoy, a CTLA-4 antibody approved in the United States in March 2011 and recommended for approval in Europe in May 2011, was shown at ASCO 2010 to improve survival in previously treated metastatic melanoma. At ASCO 2011, Yervoy was shown to improve survival in treatment-naïve patients in combination with chemotherapy. Patients who respond to Yervoy typically have durable responses in excess of 1 year, with a large subpopulation (nearly 20%) enjoying prolonged overall survival. With the possibility of using Yervoy in other solid tumors, the $2.4 billion investment that BMS made in acquiring Medarex, the original developer of Yervoy, appears to be beginning to pay off.
Vemurafenib, a BRAF-targeted tyrosine kinase inhibitor, improved survival versus chemotherapy in metastatic melanoma patients with an activating BRAF mutation that is responsible for the tumor growth. Approximately 50-70% of metastatic melanoma patients have a BRAF mutation. Responses to vemurafenib are quick and dramatic, however, patients ultimately develop progressive disease presumably due to a resistance mechanism to the drug. Plexxikon, the original developer of vemurafenib, entered into a commercialization agreement with Roche in 2006. Before Roche sealed full rights to the drug, Daiichi Sankyo acquired Plexxikon for an upfront fee of $805 million in February 2011 with potential for an additional $130 million in milestones upon approval. In unprecedented fashion, rivals Roche and BMS announced at ASCO that they intend to jointly fund research in the combination of vemurafenib and Yervoy. The hope with this combination is that patients with a BRAF mutation can enjoy the quick and dramatic tumor shrinkage from vemurafenib and allow Yervoy to maintain this response to prolong survival beyond the expectation of either drug alone.
Again, in the theme of personalized medicine, ASCO 2011 was witness to further follow-up of data from crizotinib (Pfizer) in non-small cell lung cancer (NSCLC) patients with an EML4-ALK rearrangement. This biomarker spurs cancer growth in NSCLC much like the BRAF mutation in melanoma or an epidermal growth factor receptor (EGFR) mutation in NSCLC. The EML4-ALK translocation occurs in only 4% of NSCLC, but the drug is exquisitely sensitive in these patients, allowing for a long duration of therapy.
“Both agents represent examples of accelerated drug development that can be achieved with a predefined biomarker.”
By clearly understanding the molecular pathways that are driving tumor growth in individual patients, significant advancements are made in patient care that are exemplified by vemurafenib and crizotinib. Not only does such progress improve outcomes for these select patients, but it also spares patients unlikely to respond from the toxicities of an ineffective treatment as well as the emotional toxicity associated with non-response to therapy.
Vemurafenib and crizotinib are also examples of the progress that can be made in pharmaceutical research and development. Both agents represent examples of accelerated drug development that can be achieved with a predefined biomarker. Vemurafenib entered Phase I in late 2006. Roche filed for approval simultaneously in the United States and Europe in May 2011. With accelerated approval in the United States likely, the drug could progress from IND to market entry in five years. Crizotinib has followed a similar path. It entered Phase I in 2007 and Pfizer filed simultaneously for approval in the United States and Japan in March 2011. Both situations represent best practices in oncology — accelerating development time to increase the revenue-generating life of the agents. However, both agents are not cures for these respective populations, representing additional opportunities for other agents.
Patients: affordability continues to be a hot issue
With all the potential success being evident regarding the treatment of patients with cancer, there remains a tough aspect for consideration — affordability. Many patients experience tremendous challenges when it comes to paying the medical costs of treating their cancer. In a presentation “A randomized phase II study to compare the efficacy of panitumumab plus mFOLFOX6 to bevacizumab plus mFOLFOX6 in patients (pts) with previously untreated, unresectable metastatic colorectal cancer (mCRC) expressing wild-type KRAS,” oncologist Dr. Lee Schwartzberg commented that “there is a growing awareness that the cost of cancer treatment is unsustainable.” Part of the issue is that oncologic agents are expensive and often administered over lengthy periods of time. Added to this, incoming ASCO President Dr. Michael Link was quoted by Reuters as saying, “We’re thrilled with what we consider to be breakthroughs and wonderful new therapies… yet the barriers for some patients to get them is insurmountable.” The article went on to note that the National Cancer Institute (NCI) estimates the costs of cancer care in 2010 in the U.S. will top $124 billion and could reach at least $158 billion by 2020. (Reuters: By Debra Sherman CHICAGO | Mon Jun 6, 2011 2:13pm EDT).
“Ultimately, despite being a challenge, research and policy initiatives need to better help patients cope with the cost of cancer care.”
Jeffrey Peppercorn, MD, MPH, presented on different aspects of the cost of cancer care. He noted the shifting of costs onto the patients in the form of higher premiums, co-payments and deductibles, in a setting in which costs are being driven higher due partly to innovation and the ability to do more for the patients. He added that even with financial assistance programs, one-third of patients with cancer report having trouble paying their bills and up to 25% report having exhausted their savings. (The Kaiser Family Foundation. National Survey of Households Affected by Cancer (Publication #7591)). It is difficult for practicing oncologists to advise regarding the cost of oral medications and out-of-pocket expenses owing to the tremendous diversity in coverage plans’ deductions and co-payment requirements. Ultimately, despite being a challenge, research and policy initiatives need to better help patients cope with the cost of cancer care.
In a maelstrom of information, progress is paramount
Outgoing ASCO President Sledge emphasized in his presidential address that physicians need to maintain compassion for fellow human beings and remain the primary source of information for those devoted to oncology. In a world of new therapeutic advancements, encouraging results with new agents such as crizotinib and vemurafenib are demonstrating improved outcomes for selected patients. However, careful review of the various components over time leads one to picture progress in which patients are increasingly able to look forward to personalized medicine and hopefully at a manageable cost, with compassion and under humane conditions.
About the authors:
Ian Hicks (firstname.lastname@example.org), Senior Vice President, Gordon Gochenauer (email@example.com), Director, Thierry Devevey (firstname.lastname@example.org), Director, Europe, Reviewing editor: Stephanie Hawthorne (email@example.com), Director
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