ASCO Policy Change Creates Massive Avalanche of Pre-Meeting Data

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For a diverse spectrum of stakeholders, the annual American Society of Clinical Oncology (ASCO) meeting is one of the biggest, most significant events of the calendar year. Information disclosed at ASCO can move world financial markets, seriously affect the bottom lines of drug and biotech companies, capture the attention of government regulators, alter managed care company protocols and practice guidelines, change the way oncologists practice medicine, and offer new hope to struggling patients.

Thus, when ASCO decision-makers decided to revise the manner in which they disseminate eagerly anticipated clinical research data prior to this year’s recently adjourned 44th annual meeting held at the McCormick Place Convention Center in Chicago, from May 30 through July 3, 2008, the news made headlines and made reverberations that were felt throughout the worlds of oncology research, practice, finance, and investment.

In the past, ASCO members were granted an advance look at the data that were going to be presented at the upcoming annual meeting. Critics charged that ASCOs early disclosure policies enabled both ASCO members and well-positioned investors with ASCO membership contacts to leverage the advance information, thereby outmaneuvering their competitors and getting a valuable jump on the broader market. Over the past few years, for example, even casual market observers were able to ascertain which companies were going to release positive data and which companies were going to release negative data, simply by the watching the up or down movement of a given company’s share price in advance of the meeting.

In an effort to make the process of information access fairer and more uniform, ASCO has toughened its policy, eliminating the practice of early data disclosure to its membership. Instead of send- ing members a book of abstracts several weeks in advance, as it had done up until this year, ASCO made information available all at once, lifting its embargo at 9 o’clock P.M., Eastern Standard Time, on May 15, 2008, roughly two weeks before the commencement of its annual meeting on May 30.

The immediate result of ASCO’s new disclosure method was an almost overwhelming cascade of data from almost 5,000 clinical studies. Hidden within the tsunami of released data, are studies that will move the market, seemingly small details that could dramatically weight down or lift up per-share prices of large concerns, and endpoint results likely to determine the futures of several upstart, single-product biotechs.

Now that the smoke has settled and the gambles have been made, it is easier to determine the winners and losers of ASCO 2008. One effect of the ASCO policy change is that this year’s marketplace results, instead of being influenced by whispered nuggets of information between people ‘in-the-know,’ were based more on the actual clinical performance and quality of research produced. Measured by this yardstick, a mix of big industry players (such as Novartis, Amgen, and Genzyme) and smaller concerns (BioVex, Nektar) posted impressive accomplishments:

â–º Novartis

Novartis scored a major step forward in the realm of kidney cancer therapy. According to a phase III trial released with the rest of the ASCO data, product candidate RAD001 (everolimus) delayed progression of disease by a year, in nearly two-thirds of the study patients taking the oncedaily drug. This was a significantly better result than in those taking placebo (of whom 37% sustained disease-free progression for one year). The late-stage trial was stopped early because it met its main target.

Other RAD001 data were released at ASCO. In all, four oral sessions as well as several poster sessions featured RAD001.

Perhaps more impressive than any one positive study was the company’s overall commitment to the oncology sector as evidenced by the sheer scope and quantity of the research published by Novartis at the meeting. Novartis Oncology’s cancer therapies were the subject of more than 170 abstracts at ASCO. In addition, Novartis drugs were the subjects of seven oral presentations.

Also, the first efficacy results from the ABCSG-12 study, looking at the effect of Zometa (zoledronic acid) on disease-free survival in patients with early-stage breast cancer, were highlighted in a plenary session. Findings indicated that Zometa (zoledronic acid), prescribed to prevent fractures in breast cancer patients whose tumors have spread, may actually help slow the cancer itself. The study suggests the drug may be useful for more patients with breast cancer. According to researchers, 23% of women who received Zometa had tumor cells in the bone marrow after three months, compared with 36% of those who did not get the drug. “Tumor cells are continually being released from the primary tumor,” Rebecca Aft, MD, Barnes Jewish Hospital and Washington University, St. Louis, said in a statement. “It is thought that the bone marrow harbors these cells and that these cells are likely to evolve into metastatic disease. We think that zoledronic acid changes the bone marrow so that cancer cells are unable to lodge there.”

â–º Amgen

Amgen had a fair amount of good news to disseminate at ASCO. The company said that denosumab cut the risk of bone fractures in patients with cancer, outperforming Novartis' Zometa in an early stage trial.

Denosumab reduced the risk of skeletal related events in 64% of patients, compared with 37% of those taking Zometa, according to the newly released data. The trial of 111 people included mostly patients with breast and prostate tumors, two types that often spread to the bones as cancer worsens.

In preliminary results of another denosumab trial released yesterday by ASCO, denosumab helped shrink or slow growth of bone tumors in 13 of 15 patients. Amgen is moving forward with larger human trials. A preponderance of denosumab-related data were published at this year’s ASCO. Amgen also presented data featuring Vectibix (panitumumab), Aranesp (darbepoetin alfa), and emerging clinical data from seven studies on four investigational therapies for patients with advanced solid tumors, encompassing a range of positive outcomes, phases and cancer types, were presented.

â–º Genentech

Among the data Genentech released was a phase II trial comparing Avastin (bevacizumab), combined with irinotecan (Camptosar) chemotherapy, to Avastin alone in patients with relapsed glioblastoma multiforme (GBM), the most common and aggressive type of brain cancer. Genentech said results show median survival was 9.2 months in the Avastin-only arm and 8.7 months in the Avastin and irinotecan arm. As assessed by independent radiological review, 43% of GBM patients treated with Avastin alone and 50% of patients treated with Avastin in combination with chemotherapy lived without the disease advancing within six months.

“Avastin, both as a single agent and in combination with irinotecan chemotherapy, may improve survival compared to what would be normally expected for this devastating disease,” stated study investigator Timothy Cloughesy, MD, University of California, Los Angeles, in a statement. According to historical estimates, only 15% of patients with relapsed GBM would be expected to live without their cancer advancing within six months, he said. The drug, designed to combat tumors by cutting off their blood supply, is already approved to treat colon, lung, and breast cancer.

Genentech also announced that finalized results of a phase III trial of Avastin for early-stage colon cancer will be available sooner than previously thought, said Genentech, because of faster data collection and more enrollable patients with the disease. Data will be available in 2008—a full year earlier than previously planned. In addition, the company announced results from studies of several investigational agents targeting the biological cancer pathways of HER (human epidermal growth factor receptor) signaling, Hedgehog signaling and apoptosis (programmed cell death).

Other positive data presented by Genentech featured studies demonstrating Herceptin (trastuzumab) and Avastin efficacy in a variety of cancer types.

â–º BioVex

BioVex, Woburn, Massachusetts, touted data from a phase II trial of Oncovex (GM-CSF) which demonstrated an impressive rate and durability of response in patients with advanced metastatic melanoma. The trial, in which a single arm of 50 patients with unresectable stage IIIc and stage IV metastatic melanoma received treatment with Oncovex, was designed to measure overall objective response, which is defined as a complete response (CR), where disease is completely eliminated, or partial response (PR), where there is a greater than 30% reduction in disease burden. The target efficacy endpoint detailed in the phase II protocol and agreed upon with the FDA was to achieve two objective responses or stable disease for more than two months.

At the time of the abstract submission, 40 patients had been enrolled of whom 31 were evaluable; 81% had stage IV disease. With respect to systemic objective overall responses; three CRs, three PRs and two mixed responses (greater than or equal to PR of existing disease and greater than or equal to PR of lesions which became measurable after initiation of therapy) were reported. Two further patients had post-treatment objective responses and four patients had durable stable disease. All objective responses were ongoing at between four and 23 months following the patient’s first dose of Oncovex. Side effects were reported to be largely limited to mild flu-like symptoms, as expected from the phase I study.

â–º Nektar Therapeutics

Nektar Therapeutics, San Carlos, California, announced initial results from a phase I study of NKTR-102, Pegylated irinotecan. The data show significant antitumor activity in patients with refractory solid tumors. Tumor regression, antitumor activity or prolonged disease stabilization were observed in a number of cancer types, including non—small cell lung cancer, ovarian, small-cell lung cancer, cervical, adrenocortical, esophageal, and Hodgkin’s lymphoma. The study also demonstrates that Nektar’s small molecule Pegylation technology produced an increase in SN38 exposure that was up to six-fold higher than the exposure previously reported with irinotecan at equivalent doses. SN38, a topoisomerase I inhibitor, is the active metabolite of irinotecan.

The interim data reported at ASCO evaluated 27 of 32 patients in the first of three dose schedules from the phase I trial. Results for the first schedule (weekly x3 q4 wk) found antitumor activity in seven out of the total 32 patients evaluable for efficacy. Partial responses were confirmed in three patients, or 10% (greater than 30% tumor regression per RECIST), and other evidence of anti-tumor activity was confirmed in four patients, or 12% (tumor regression by more than 15% but less than 30% per RECIST, or significant biomarker evidence).

“This significant antitumor activity in a number of patients whose tumors have progressed on prior therapies makes NKTR-102 one of the most promising cancer drugs I have ever studied,” stated Daniel D. Von Hoff, MD, lead investigator, Translational Genomics Research Institute and Scottsdale Clinical Research Institute at Scottsdale Healthcare.