As a continuation of the collaboration between OBR and MDoutlook, we will be presenting you with a series of detailed post-ASH and post-SABCS trends research into the immediate clinical impact and integration of research presented at both meetings. The trends research is based on a series of Quick Polls across the MDoutlook platform of 47,000 cancer treaters globally. Feedback was collected within one week of each meeting and from more than 500 cancer treaters (approx 40% of respondents were attendees). No financial incentives were provided to participants.
The first report covers B-cell Lymphomas.
52nd ASH Annual Meeting and Exposition was held in Orlando. December 4-7, 2010.
ASH quick poll data were finalized on December 19th and included responses from 23 countries (~2/3 of responses from USA).
Quick polls are a fast way of measuring expected acceptance of clinical data post major medical meetings, and perhaps can be used to make some assumptions about adoption amongst providers. In today’s information hungry environment, the speed at which these polls can be conducted and analyzed can be advantageous for market planning and “pressure testing” acceptance of data amongst key stakeholders.
Submitted by Jan Heybroek, President, The Arcas Group
At the beginning of every year we like to recap the biggest oncology stories from the previous year. We follow the media all year long – the clinical successes, the clinical failures, the political and legislative storm, and all the highs and lows throughout the year. This year’s list contains those highs and lows too, and hopefully will remind you of what an important, dynamic, and intriguing industry cancer is. Here are the top stories of the year as we see it.
1) AVASTIN IS LIKELY TO LOSE ITS BREAST CANCER INDICATION
On July 20, an ODAC panel voted 12 to 1 recommending that the FDA revoke its accelerated approval of Genentech’s Avastin® as a treatment for metastatic breast cancer (mBC). The panel unanimously said that two follow-up studies, AVADO and RIBBON 1, failed to demonstrate enough clinically meaningful benefit to warrant its indication in women with mBC given its risks. In a blow to the Avastin franchise, the FDA announced on December 16 that it was recommending the removal of the breast cancer indication from the drug’s label and gave Genentech 15 days in which to respond to its Notice of Opportunity for a Hearing. In a letter to the FDA dated December 23, Genentech subsequently requested a public hearing to present its case as to why Avastin should continue to be marketed for the indication and said it would supply supporting documentation for the hearing by January 18, 2011.
2) PROVENGE WINS APPROVAL FOR PROSTATE CANCER—AND A NATIONAL COVERAGE DETERMINATION AWAITS
Dendreon’s prostate cancer vaccine Provenge® won approval on April 29 as the first-FDA approved autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic, castrate-resistant (hormone-refractory) prostate cancer (CRPC). The immunotherapy showed an increase in overall survival of 4.1 months—the median survival for patients receiving Provenge was 25.8 months, as compared to 21.7 months for a placebo. The cost? A hefty $93K per patient. Although the CMS rarely issues NCDs for cancer drugs, on July 1 it said it had begun evaluating Provenge to make a National Coverage Determination (NCD). In mid-November, Provenge won the support of a Medicare panel advising the US government on whether to pay for the treatment after experts reviewed the vaccine’s clinical impact on the health outcomes of patients with advanced prostate cancer. A proposed NCD will be issued by March 30, 2011. A final ruling on coverage from the CMS is expected by June 30, 2011.
3) 2010’S HEADLINE-MAKING CANCER DRUGS
A few of the biggest newsmakers of 2010 in the oncology pipeline included Roche/Plexxikon’s PLX4032, Bristol-Myers Squibb’s ipilimumab, Onyx’s carfilzomib, and Pfizer’s crizotinib.
Clinical advances were made in advanced melanoma—the novel gene-targeted therapy PLX4032 caused tumors to shrink in a majority of patients with the BRAF gene mutation in an early-stage trial, while BMS’s monoclonal antibody ipilimumab was found to improve survival in patients with the same difficult-to-treat cancer. Onyx reported full results at ASH from a mid-stage trial of carfilzomib showing that it shrank the tumors of one-third of study patients with multiple myeloma. Additionally, in patients with a rare form of lung cancer and a defect in the ALK gene, Pfizer’s crizotinib, reduced tumor size in 57% and data showed the drug also stopped the progression of the disease in 87% of patients.
Amgen’s most important new product, denosumab, showed superiority in head-to-head trials with Novartis’s Zometa® in breast cancer and prostate cancer for preventing and/or reducing skeletal-related problems. In one study, denosumab was better than Zometa at delaying fractures and other skeletal events in men with advanced prostate cancer. After a priority review by the FDA, Xgeva® (D-mab’s trade name for its cancer-related indications) was approved on November 18 as the first and only RANK Ligand inhibitor for the prevention of skeletal-related events in patients with bone metastases from solid tumors. And in top-line results from the pivotal Phase 3 ‘147 study, reported in late 2010, Xgeva significantly improved bone metastasis-free survival in men with prostate cancer by 4.2 months compared with placebo. The data showed Xgeva to be the first bone-targeted therapy to delay the onset of bone metastases in prostate cancer, Amgen said.
Update 1/11/11: One of our friends (and an OBR subscriber) at sanofi-aventis brought to our attention the fact that we overlooked adding sanofi’s recently approved prostate cancer drug, Jevtana® (cabazitaxel) Injection, as a “2010 headline-making cancer drug” in our blog. In our defense, we focused mainly on oncology drugs still in the pipeline for proposed indications.
Jevtana was approved by the FDA in June 2010 less than three months after being granted a priority review in April 2010. Results from the pivotal Phase 3 TROPIC study, the basis for Jevtana’s approval, were the first to demonstrate an overall survival advantage in patients with metastatic hormone refractory prostate cancer (mHRPC) whose disease had progressed following treatment with a docetaxel-containing treatment regimen. In combination with prednisone, Jevtana reduced the risk of death by 30% in men with mHRPC. The FDA approval filled a critical gap among patients with the most advanced stage of prostate cancer, according to sanofi-aventis.
4) HEALTHCARE REFORM IMPACTS CANCER CARE
The historic Patient Protection and Affordable Health Care Act, signed into law on March 26, will have a largely positive impact for patients with cancer. On September 23, legislation was passed eliminating the lifetime cap on what health insurance companies will pay if consumers face an expensive illness like cancer. Seniors who can’t afford expensive cancer drugs and pediatric cancer patients will both benefit from healthcare reform—by 2020 Medicare will cover 75% of drug costs in the “doughnut hole” for Medicare patients and insurers will no longer be able to exclude children with pre-existing conditions from being covered by their family policy.
President Obama also signed into law legislation preventing Medicare physician reimbursement cuts of 25% through the end of 2011. Oncologists were eager to see a permanent repeal of the flawed sustainable growth rate (SGR) formula used to set physician payments for Medicare, but they at least got a longer-term reprieve than the rest of 2010’s previous short-term fixes.
As of 2014, the new healthcare law will require health plans to pay for routine care costs for patients who participate in clinical trials for the prevention, detection and treatment of cancer and other life-threatening diseases and conditions. The new law covers care in all 4 phases of clinical trials. In addition to helping individuals get potentially lifesaving treatment, advocates hope the new law will encourage broader participation in clinical trials.
5) CANCER DRUG SHORTAGE: A PERFECT STORM
Local media in towns from Alaska to Florida reported on how community oncology practices were trying to manage patient care while coping with a lack of vital cancer therapies. ASCO reported severe and worsening shortages of many critical therapies used in cancer treatment, including but not limited to doxorubicin, leucovorin, cisplatin, etoposide, nitrogen mustard, vincristine, propofol, and morphine. Dr. Michael Link, ASCO’s incoming president-elect, said the shortage was the worst seen in 30 years and described it as “a perfect storm” with “no good explanation.” An FDA spokesperson said in October that 40% of the overall drug shortages were attributable to manufacturing problems, 20% because a manufacturer just stopped making a particular drug, and 20% because of production delays. But the underlying cause, the FDA said, was that the drugs in limited supply were not as profitable as other newer ones. Sen. Amy Klobuchar, D-Minn. announced at a December 29 press conference that she would introduce legislation to require drug manufacturers to warn the FDA of impending shortages and to ease rules on importing drugs from Canada and other countries in order to address the prescription drugs shortage, including cancer medicines.
6) NICE REJECTS VITAL CANCER DRUGS; OKAYS EMERGENCY CANCER DRUG FUND
The UK’s National Institute for Health and Clinical Excellence (NICE) approved an emergency fund of £50m starting in October 2010, to give very sick patients with cancer faster access to drugs not already approved by NICE. In the past, NICE has not been able to fund treatments that for the average patient extend life by 3 months or less.
In final guidance, NICE rejected Roche’s Avastin in combination with chemotherapy (oxaliplatin and either fluorouracil or capecitabine) for treating metastatic colorectal cancer; and also said it wouldn’t recommend Avastin in combination with a taxane as a treatment option for metastatic breast cancer on the grounds that it offers limited and uncertain benefit for patients compared with existing treatments.
In preliminary draft guidance, NICE is rejecting GlaxoSmithKline’s Tykerb® or Roche’s Herceptin® in combination with aromatase inhibitors for treating patients with hormone-receptor, HER2-positive breast cancer based on cost-effectiveness. The view is open to public consultation until January 19, 2011. In other negative recommendations issued in 2010 based on cost-effectiveness, NICE rejected GSK’s Arzerra® as a second-line treatment for patients with chronic lymphocytic leukemia (CLL). The drug rationing body also refused to back Novartis’s kidney cancer drug Afinitor® as a second-line treatment, but it hasn’t yet issued final guidance, and Novartis, which cut the price of the drug, said it would appeal the verdict.
NICE issued positive draft guidance on December 24 for GSK’s Votrient® for patients with advanced renal cell carcinoma after its manufacturer GSK agreed to lower the price. A “partial rebate” will also go to the NHS if a trial comparing Votrient to Pfizer’s Sutent®, now the standard treatment, doesn’t show comparable effectiveness with Sutent.
7) THE CHALLENGE OF CANCER GENERICS & BIOSIMILARS
The health care overhaul law signed by President Obama earlier this year permits U.S. regulators to approve copies of biological medicines like Rituxan®, creating a new market and stirring up competition. The Israeli generics company Teva Pharmaceuticals has targeted Roche’s $5 billion cancer drug in a biosimilar trial. The drug copies could save Americans $6.6 billion over 10 years, with most of the savings coming after 2013.
The FDA asked Hospira, Inc. for labeling changes to the generic version of sanofi-aventis’ breast cancer drug Taxotere® (docetaxel) in late November, delaying its approval. In July, a federal appeals court upheld a ruling that invalidated a patent on Eli Lilly’s Gemzar®, which generates $750M in US sales each year—a generic version of Gemzar was launched later in November. A federal court judge upheld a patent protecting Lilly’s Alimta®, used for both non-small lung cancer and mesothelioma. Teva had challenged the patent, which protects Alimta until July 2016. And Sun Pharma was ordered to stop selling its generic version of sanofi-aventis’ Eloxatin® (oxaliplatin) by a U.S. District Court as of June 30, 2010 until August 9, 2012, at which time the generic manufacturers would be authorized to sell generic oxaliplatin products under a license, before expiry of the patents at issue.
The FDA approved the sale of a new generic version of AstraZeneca’s Arimidex®, used to treat breast cancer and ovarian cancer in post-menopausal women, in June. In terms of cost, the FDA’s action was hailed by one oncologist as a “big deal.” APP Pharmaceuticals Inc. received FDA approval in November to market topotecan for injection—the therapeutic equivalent of GSK’s Hycamtin® indicated for both small-cell lung cancer and cervical cancer.
Celgene faces a generic challenge from Natco Pharma in India, and from Watson Pharmaceuticals in the U.S. to sell a copycat version of Revlimid® before its patent protection expires. Celgene recently raised the price for the blood cancer drug by 4.5% in the U.S., bringing its cost to about $85,000 per year.
Update 1/6/11: Spectrum Pharmaceuticals just announced a deal on Jan. 5 with Viropro Inc. to develop a biosimilar version of Rituxan, ahead of its U.S. patent expiration in 2015.
Update 1/10/11: A third drug company is now in the race to produce a biosimilar of rituximab—in addition to Teva and Spectrum Pharmaceuticals (the latter company just announced a deal on 1/5/11 to develop a Rituxan biosimilar), Novartis’ Sandoz unit announced today, 1/10/11, that it is starting Phase 2 trials of the monoclonal antibody in rheumatoid arthritis and plans to also develop a biosimilar of the blockbuster drug.
8) RADIATION DANGERS AND CANCER RISKS
The danger to consumers/patients from radiation exposure from medical diagnostic tests was increasingly publicized in 2010. Two breast screening studies published in August in Radiology highlighted the issue and The New York Times ran a series of articles documenting the sometimes crippling effects of radiation overdoses that resulted, in part, from the inability of regulators and the medical community to keep pace with rapid technological advances in the industry. The FDA announced in April that it was taking steps to reduce overdoses, under-doses and other errors in radiation therapy by strengthening the agency’s approval process for new radiotherapy equipment after an analysis revealed extensive errors in using the devices over a 10-year period.
9) A LUNG CANCER SCREENING TEST THAT CAN SAVES LIVES
A significant 8-year study funded by the National Cancer Institute showed that screening current and former heavy smokers with low-dose computed tomography scans resulted in 20% fewer deaths from lung cancer compared with a standard chest X-ray. It is the first time that a clear benefit had been shown for any form of lung-cancer screening. The study, called the National Lung Screening Trial, involved more than 53,000 people ages 55 to 74 with a smoking history of at least 30 “pack years.” The study made news because lung cancer, mainly linked to smoking, is typically caught late, once the cancer has already spread, making it the #1 cancer killer.
10) END-OF-LIFE CANCER CARE
Under a new policy outlined in a Medicare regulation, starting on January 1, 2011 the government will pay doctors who advise patients on options for end-of-life care, which may include advance directives to forgo aggressive life-sustaining treatment. The new rule allows annual discussions as a part of yearly wellness visits or physical examinations which are covered by Medicare and were signed into law with final healthcare legislation last March.
A study published in the September 13 issue of the Journal of Clinical Oncology found that patients with cancer who died in a hospital or intensive care unit had a worse quality of life than those who died at home with hospice, and their bereaved caregivers were at increased risk for developing a psychiatric illness. The findings came just a month after a landmark New England Journal of Medicine study showing that receiving early palliative care—which focuses on relieving distress in patients and caregivers alike—actually helps patients live longer. Another major study from researchers at the Dartmouth Atlas of Health Care found that one in three patients with advanced cancer spend their final days in hospitals receiving costly, aggressive treatments they might not want. Dr. David Goodman said the study had the potential to spark meaningful conversations about end-of-life care, but it could also fuel concern about rationing healthcare.
Update 1/5/11: The administration announced on 1/4/11 that they were reversing course and revising the Medicare regulation to delete references to end-of-life planning as part of annual physical examinations covered under the new health care law (see OBR daily’s Jan. 4 edition for a link to the complete article from the New York Times under our Healthcare & Pharma News Headlines).
Feel free to comment if you feel we missed anything.
by Nancy Ciancaglini