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January 19, 2010 - 06:01 pm Posted in Featured comments0 Comments

Cancer Highlights of 2009

1) Biggest Biotech Deal To-Date
After an eight-month battle, Roche finally gained control of its longtime U.S.-biotech partner Genentech in a $46.8 billion takeover deal to reinforce its leading position in cancer medicines. Genentech's board and shareholders ultimately accepted the Swiss drug maker’s offer of $95 a share for the 44 percent of the company it didn't already own; the buyout was completed in March and Roche will rebrand its U.S. medicines as Genentech, including non-biotech drugs. In addition, Roche will drop its long-standing membership in the PhRMA (Pharmaceutical Research and Manufacturers of America) trade group in favor of the Biotechnology Industry Organization (BIO).

2) USPSTF Breast Cancer Screening Recommendations Stir Controversy
Controversial new breast cancer screening guidelines issued in November by the U.S. Preventive Services Task Force (USPSTF) dropped widely-held guidance that women get routine annual mammograms starting at age 40. Instead, the guidelines now advise women ages 50 to 74 could be screened every other year, while those in their 40s should make an individual decision after talking with their doctors. The new guidelines shook up the clinical norm on breast cancer screening and ignited a public debate that dominated the news as 2009 came to a close. On the heels of the task force’s announcement, the American College of Obstetricians and Gynecologists (ACOG) announced revised recommendations for Pap tests, saying young women should begin getting the cervical-cancer screening test at a later age and at less frequent intervals than previously recommended.

3) Pricey Cancer Drugs—Here to Stay?
With Allos Therapeutics’ newly approved lymphoma drug Folotyn™ reported to cost $30,000 per month, and GlaxoSmithKline’s new drug Arzerra™, approved for chronic lymphocytic leukemia, reported to cost up to $98,000 for a six-month treatment course, cancer drug costs once again made major headlines. Drug makers have primarily defended the cost of these expensive drugs for rare cancers, and other high-priced cancer treatments, by saying that they fulfill an unmet need for patients who have either few or no treatment options. But critics say that the therapies don’t provide enough benefits to patients to merit the high prices. In the U.K. in November, the National Institute for Health and Clinical Excellence (NICE) issued draft guidance against recommending Nexavar® for advanced liver cancer for reimbursement on the National Health Service (NHS) saying the price being asked by the drug’s manufacturer Bayer was simply too high compared to “better value cancer treatments.” Although NICE indicated it had changed its approach to appraising high cost treatments—with more treatments which could extend life for terminally ill patients being recommended—the advisory body seemed to have held its ground on allowing coverage for a number of the more expensive cancer therapies during 2009. Late in the year, for example, it turned down the use of Avastin® for the treatment of metastatic colorectal cancer, saying that the drug “did not represent a cost-effective use of NHS resources.”

4) Health Care Reform’s Impact on Oncology
The future of the U.S. cancer care delivery system and access to high quality cancer care for patients was increasingly jeopardized in 2009 due to proposed cuts for CY2010 from the Centers for Medicare and Medicaid Services (CMS). But influential cancer groups including ASCO, COA, US Oncology, ASTRO and others voiced their concern with legislators and pulled off several key victories which should impact oncologists and cancer patients more positively than anticipated earlier in the year when a final health care bill is agreed upon by both the House and Senate in early 2010.

Health care reform legislation is estimated to spend between $850 billion and $1 trillion in the industry funded by new taxes, and cuts to insurers, PhRMA, hospitals and other providers, with lessened cuts to core businesses of medical oncology, radiation oncology, office-administered drugs and PET/PET-CT imaging.

The President signed the law that will create a short term patch to Medicare’s Sustainable Growth Rate (SGR) formula, averting the 21 percent cut to Medicare physician payments from taking place for two months. The patch runs through February 28, 2010. It is anticipated that future legislation will permanently eliminate or delay the built up Medicare physician payments cuts currently required by the Sustainable Growth Rate (SGR) formula.

The legislation expands the privately-insured patient population in need of cancer care, eliminating pre-existing condition exclusions and rescissions.

The removal of prompt pay discounts of up to 2 percent from the Average Sales Price (ASP) calculation, not included in either the House or Senate health care bills, is unlikely to be included in final legislation. But oncologists' felt they had made progress with legislators on the issue.

In the final rule issued in October, CMS eliminated consultation codes entirely, in both the inpatient and outpatient/office setting. According to ASCO, eliminating consultation codes will disadvantage physicians, like most oncologists—a recent analysis suggests that medical oncologists will experience a decrease of 28 percent in Medicare reimbursement as a result. ASCO supported an amendment to the Senate bill which would delay the elimination of consultation codes for one year. The amendment could come up again when the House and Senate bills are reconciled.

It's likely that a provision requiring insurance companies to cover routine care costs associated with a clinical trial will be a part of the final legislation crafted.

Although the House passed a bill including a new Medicare benefit that will pay physicians to have advance care planning/end-of-life counseling discussions with patients, the Senate's version of the bill did not. It's uncertain if the provision will be included in the final bill.

Within health care reform legislation, oncology practices are likely to benefit from the creation of pilot Accountable Care Organization (ACO) programs for Medicare and Medicaid providers. A provision was included in the House bill that will allow oncologists to form ACOs and share in savings that accrue to Medicare through the use of evidence-based pathways, disease management and advance care planning. US Oncology, for one, is working to ensure that the provision remains in the final health care legislation enacted in 2010.

5) Personalized Medicine Makes Strides
In big clinical findings at ASCO, a Phase 3 study of Herceptin® significantly prolonged the lives of patients with HER2-positive advanced stomach cancer when combined with standard chemotherapy. In advanced melanoma patients with a mutated BRAF gene, patients showed significant tumor shrinkage when given an experimental drug being co-developed by Roche and Plexxikon known as PLX4032. Data from a small, early-stage study indicated that the drug prevents progression of the disease for six months. In other news, Genomic Health’s Oncotype DX® colon-cancer test, based on an analysis of seven different genes found in colon-cancer tumors, indicates whether patients are at low, intermediate or high risk of having the disease return after it is surgically removed. And in March of 2009, cancer doctors at Massachusetts General Hospital announced that genetic testing would become a commonplace aspect of treatment for nearly all new cancer patients within a year. Doctors plan to screen for 110 abnormalities, carried o
n 13 major cancer genes, that predict whether drugs on the market or in development might thwart a patient’s tumor.

6) 2009 Clinical Trial Successes & Failures

Successes:

  • A pivotal Phase 2 study of T-DM1 showed that the experimental drug shrank tumors in 33 percent of critically ill breast cancer patients whose disease no longer responded to treatment with either Herceptin or GlaxoSmithKline's Tykerb® and patients went an average of 7.3 months before their tumors began to grow again.
  • In advanced head and neck cancer, Erbitux® increased survival by 20 percent when added to initial chemotherapy, compared with chemotherapy alone. Researchers also saw a 46 percent increase in progression-free survival.
  • Data from a Phase 3 study of Provenge™ demonstrated that the prostate cancer vaccine extended the average survival of patients by four months compared with a placebo, nearly twice as long as the best available chemotherapy, and increased three year survival by 38 percent. The FDA is scheduled to make an approval decision on the drug on May 1, 2010.
  • OncoGenex Pharmaceuticals’ new cancer drug, OGX-011, extended the survival of patients with advanced prostate cancer by almost seven months when combined with Taxotere®, based on results from a Phase 2 study.
  • Eli Lilly’s Alimta® increased overall survival after standard chemotherapy by 50 percent for advanced lung cancer patients in a large, international trial, establishing the drug as a new standard of care in maintenance therapy for advanced nonsquamous non-small cell lung cancer.
  • Onyx's carfilzomib significantly reduced multiple myeloma in 45 percent of patients who didn’t respond to as many as three previous therapies in a Phase 2b study.
  • Sanofi-aventis/BiPar’s investigational PARP1 inhibitor, BSI-201, improved median overall survival from 7.7 months to 12.2 months in patients with metastatic triple-negative breast cancer (mTNBC) when added to gemcitabine and carboplatin (GC), based on updated overall survival data presented at SABCS.

Failures:

  • Avastin failed the large, closely watched C-08 trial as an adjuvant treatment in early-stage colon cancer. But the year was hardly a total clinical washout for Avastin–it won FDA approval as a single agent for previously treated glioblastoma, the first new drug for the disease in a decade, and was also approved for metastatic renal cell carcinoma in combination with interferon.
  • Poniard’s chemotherapy drug picoplatin failed to significantly prolong survival in patients with advanced small cell lung cancer based on pivotal Phase 3 study results disclosed in November, dashing hopes for the company’s initial FDA approval filing. Picoplatin then showed some moderate success in a colon cancer trial.
  • Synta announced disappointing preliminary results from the Phase 3 Symmetry trial of elesclomol in metastatic melanoma when the study's primary endpoint of progression free survival (PFS) failed to show statistical significance except in a small subgroup of patients. Trials of elesclomol were halted earlier when a higher death rate among patients taking the experimental drug was observed.
  • Preliminary data from Genta’s Phase 3 trial of Genasense® in advanced melanoma failed to show a statistically significant benefit for its co-primary endpoint of progression-free survival. Data for the other co-primary endpoint of the trial, overall survival, was still too early to evaluate in 2009.
  • Pfizer halted a late-stage trial of figitumumab in non-small cell lung cancer, after an analysis showed that it would be unlikely to meet the main goal of improving overall survival when added to two older therapies—paclitaxel and carboplatin—compared with the standard therapy of paclitaxel plus carboplatin alone. Pfizer stopped enrolling patients in the study several months earlier due to a greater number of negative events in the trial’s figitumumab arm, including death.

Some of the more high-profile drugs that were turned down for FDA approval and/or which received a no-go from the Oncologic Drugs Advisory Committee (ODAC) included:

  • An FDA advisory panel rejected Roche/OSI Pharmaceuticals’ Tarceva® as a first-line maintenance treatment in non-small cell lung cancer, saying the treatment benefit was modest compared with other available therapies (Tarceva’s approval fate should be decided by April 18, 2010, its PDUFA date);
  • Vion’s Onrigin™ as a single agent for patients 60 years of age or older with poor-risk acute myelogenous leukemia (AML);
  • GTx’s Acapodene® for the reduction of fractures in men with prostate cancer on androgen deprivation therapy (ADT); and Genzyme’s Clolar® for use in adult patients with acute myeloid leukemia (AML).

Click on the image below to view the table of 2009 FDA APPROVALS OF ANTI-CANCER AGENTS:

Year End Financial Summary

Click on the image below to view the table of 2009 MARKET PERFORMANCE:

Click on the image below to view the table of 2009 TUMOR TICKER TOP 5 WINNERS & LOSERS:

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January 06, 2010 - 06:01 pm Posted in Featured comments0 Comments

No Magic Bullets for Drug Price Reform:
Notes from ASH and SABCS

By Neil Canavan

ASH: The High Cost of an Unmet Need
Andrew Pollack, a journalist from the New York Times, set the 2009 ASH in motion with his front-page, opening-day article, “A Fortune to Fight Cancer”, which highlighted the record-setting price of Folotyn. Approved in September ‘09, Folotyn, manufactured by Allos, Westminster, CO, is indicated for the treatment of peripheral T-cell lymphoma. According to clinical trials, the drug is adept at shrinking tumors, and thereby extending progression-free (but not overall) survival—so, to be clear, the patient may well be more comfortable, but will not live longer. And the price? It’s roughly $30k a month.

The article appeared just as several Allos/Folotyn posters were being presented at ASH, and poster presenters hastily deferred all questions from the press to the nearby-stationed, Monique Greer, Vice President of Allos’ Corporate Communications. “Well, it did generate a lot of awareness for a small company,” Greer observed, in the sense that there’s no such thing as bad publicity. “But once we got past the headline it enabled us to get into the discussion about how rare this disease state really is, and the fact that it has a very poor prognosis.”

Greer also suggested an angle to the economics concern: the drug requires little of supportive care; it’s administered on an outpatient basis; and only requires a few minutes in an I.V. push. She further pointed out that doctors were more interested in the drug’s mechanism of action and response rates, rather than its price. What Greer says she hears from patient advocates is that they understand what’s at stake in drug development.

Judy Jones, President of the Cutaneous Lymphoma Foundation, is by no means a cheerleader for drug prices based on whatever the market will bear, but in a telephone interview she was sympathetic to certain arguments. “We’re dealing with a new treatment for a disease that has no FDA approved treatment. Until this drug came along these patients didn’t have anything. Do I wish that these [new] drugs were cheaper? Absolutely. But I don’t know how to determine how much is too much, and I don’t want to threaten new drug development.”

A day after Pollack’s article appeared in the Times, a seemingly prescient talk at ASH, titled, “The Cost of Health Care: Balancing a Patient's Right to Care with the High Cost of Some Drugs and Procedures” suggested that the issue of drug pricing might be addressed. But that was not the case. What the speaker, economist Paul Ginsburg, President of the Center for Studying Health System Change, Washington, D.C., did discuss were those cost-drivers common to the healthcare system as a whole where, in general, many highly effective drugs are now, or soon will be, off-patent.

This is not the case, of course, for cancer treatments. “I quickly realized during the course of the meeting that in oncology, one of the biggest issues is drug pricing,” he said, and he’s wary of the competing interests in trying to bring down costs. “All spending is someone else’s income,” Ginsburg said, adding that oncologists have long standing conflicts of interest because they sell drugs directly to the patient, and are, in fact, competing with pharmacies when it comes to oral vs. I.V. medications. “In the industry these are called self-referral incentives,” he said, “like if a physician orders a CT scan, and s/he just happens to also own a CT scanner.”

SABCS: The Race Heats Up
Healthcare reforms are coming, to be sure; but just how elegant or crude the reforms will be may depend largely on the body of the reformers. “The oncology community would do itself a favor by taking this issue seriously instead of constantly excepting the idea that anything that works at any price has to be good,” said Hal Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston, MA. His comments came after the SABCS presentation of promising data for a combination treatment of Herceptin (trastuzumab) and Tykerb (lapatinib) in the setting of metastatic breast cancer (Abst. #61)—a regimen that will run a minimum of $15,000 a month, for a payoff of just over four months of increased survival.

Burstein is also concerned with the very language used in the reporting. He responded to the headline-reporting of data for the so-called PARP inhibitor, BSI-201. “The Times said, ‘drug improves survival’, which is true, it improves by two months, meaning, May vs March.” But some patients misunderstood the language, thinking they now had a shot at an actual cure, which could easily drive demand for something that is only minimally effective.

Also reported at SABCS were results from Avastin’s AVADO and RIBBON trials, where success was measured, as with Folotyn, as gains in progression-free survival. Matthew Ellis, MB, PhD, Director of the Breast Health Program, Washington University and Barnes-Jewish Hospital at St. Louis, MO, said “we need to be careful about approving drugs that don’t improve survival, yet cost $50k to $60k a year.”

Gabriel Hortobagyi, MD, Director of the Breast Cancer Research Program at the M.D. Anderson Cancer Center, Houston, TX, concurs: “Multiply [that] by the number of breast cancer patients out there, and pretty soon we’re talking about real money.” And money begets money. Profits are put back into research that hopefully will lead to more drugs, and more profit. But therein lies part of the problem. “In oncology,” said Hortobagyi, “we do a huge amount of research on drugs, and very little research in biomarkers,” the biological signals that could tell you if the drug is working, or, before the drug is even given, if it even has a chance of working. He also said that “to do healthcare reform right, competitive efficiency [of treatments] has to be provided with a reasonable funding mechanism.”

As the clinicians wait for these assays to determine who might actually benefit from a given drug, the philosophical task of defining benefit must be addressed. “That is the debate to be had by everyone,” asserts Mothaffar Rimawi, MD, Baylor College of Medicine, Houston, TX. The community of physicians needs to comment on it, and the community of patients and patient advocates also need to comment on it. “What is the dollar value we put on a month gained, or the quality of a life briefly improved? This is a very sensitive discussion. Is your position that of having a loved one who is a patient, or are you a policy maker who has a limited number of dollars to stretch?”

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