Replies to post #5929 on Biotech Values

[DewDiligence]

FDA Moves Cancer Cures Into The Slow Lane

[Musings from yet another newsletter author. The subject is Accelerated Approval.]

http://www.forbes.com/investmentnewsletters/2005/01/18/cz_sg_0118soapbox_inl.html?partner=yahoo&...

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Scott Gottlieb, MD,
Forbes/Gottlieb Medical Technology Investor
01.18.05

NEW YORK - I have been warning for some time that the recent criticism of the Food and Drug Administration could lead to a dangerous backlash inside the agency, with rank-and-file medical reviewers taking an increasingly cautious approach to the approval of important new medicines. Recent events indicate that the backlash may be here.

First, there was a lopsided vote in early December by an FDA advisory committee not to recommend approval of the testosterone patch for women called Intrinsa, developed by Procter & Gamble (nyse: PG - news - people ). Next, there was the vote last week by another FDA advisory committee not to recommend over-the-counter status for the cholesterol-lowering drug Mevacor. This was the third time the FDA had been asked to switch the drug for sale over the counter, the same way it is sold in England, and after sending signals that the agency was open to the concept for Americans, the lopsided "no" vote surprised observers.

Even more concerning, there is also a whiff of caution coming from the agency's cancer division--the Oncology Drug Advisory Committee (ODAC)--where delays on the approval of new drugs can have a dramatic impact on the lives of patients who are suffering from terminal disease.

At a meeting last month, outside advisers to ODAC as well as rank-and-file FDA medical reviewers expressed criticism of the applications they are seeing and a desire to clamp down on the number of cancer drugs qualifying for accelerated approval. Accelerated approval regulations allow the FDA to approve products based on preliminary test results, with the proviso that the company continues with clinical trials after the drug is marketed. The chair of the FDA's cancer drug advisory committee rejected the idea that cancer drugs should be allowed onto the market if they are reasonably safe and have some degree of effectiveness (known as "efficacy") with the understanding that oncologists will determine their value through routine use of the drug.

If the tenor of the discussion at the advisory committee is any guide, then the FDA could take a much harder stand when it comes to the accelerated approval of new cancer drugs--requiring overwhelming evidence that a drug can melt away the majority of tumors before qualifying it for rapid approval. This could add years to the development of new cancer drugs, and require more of them to undergo all three phases of clinical trials, rather than letting the most promising new drugs that target unmet medical needs onto the market after only two rounds of clinical study, as is now customary.

The other point of contention at the cancer advisory meeting was whether it is appropriate for the FDA to require drugs up for accelerated approval for treatment of a specific kind of terminal cancer to prove that they were superior to other drugs being used off-label to treat the same cancer.

The debate turned on the FDA's consideration of Inex Pharmaceutical's application for accelerated approval of Marqibo vincristine sulfate liposome injection to treat relapsed, aggressive non-Hodgkin's lymphoma (NHL). The FDA noted that no products have been approved for the indication, and suggested that the committee consider whether a number of products that are used off-label for the indication should be considered "available therapy." By suggesting that ODAC consider off-label uses as available therapies, the FDA dramatically raised the bar for approval of Marqibo.

If this policy stands, and if the FDA's cancer division starts comparing drugs up for accelerated approval to other cancer medicines that are used off-label to treat the same disease, don't expect many cancer drugs to get through the accelerated approval process. The FDA could feel vindicated in pursing this policy after the recent failure of the AstraZeneca (nyse: AZN - news - people ) drug Iressa--which had been approved through the accelerated process--to prove that it not only shrunk lung cancer tumors but also helped people live longer.

All of this could be bad news for the biotech companies that are working on new cancer drugs. Most of these companies already lose gobs of money raised from investors to move their most promising compounds through the drug development process. There is a finite amount of investment capital available for these money-losing activities.

There are other drug reviews underway that may signal whether the FDA is heading toward even more caution. These include the agency's review of an important new inhaled version of insulin by Pfizer (nyse: PFE - news - people ) called Exubera, its review of a new drug for diabetes by Amylin (nasdaq: AMLN - news - people ) called Symlin, and its consideration of a new drug for myelodysplastic syndrome by biotech company Celgene (nasdaq: CELG - news - people ) called Revlimid.

At the FDA, there's a standard refrain inside the drug review divisions in the face of any doubt: Ask for more information. That refrain is costly, not just in dollars, but also in lives. Making cancer trials longer, or asking companies to complete more rounds of testing, will delay getting drugs to patients who need them. Further, it will force companies to spend money that could otherwise be earmarked for development of other drugs. Already, the approval process that involves testing new medicines in people can take as long as ten years and cost nearly half a billion dollars. Adding more patients to a trial costs an average of $20,000 per patient. This money comes directly out of the research and development budgets of biotech companies.

Especially for cancers that have resisted conventional treatment, it is not always easy to compare one drug to another and say a treatment is clearly superior. It takes many years of study and clinical practice to make these subtle distinctions. Even then, choosing a last-line medicine often comes down to a very personal decision by a patient and his doctor about how many painful side effects the patient is willing to tolerate for a particular chance at life.

If the FDA's new cancer policy stands, and if the agency continues to take a go-slow approach to new drug approvals, this personal decision is going to be more often made inside the FDA. A fresh crop of caution inside the FDA may keep the agency out of the news, but it won't keep my cancer patients from dying.
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[DewDiligence]

FDA Names Dr. Richard Pazdur to Lead New Cancer Office

[As Dr. Pazdur is known for being a statistical nitpicker (#msg-4881843), I wonder if this news, though expected, is part of the reason DNDN is down today. In any event, I just bought more.]

http://www.fda.gov/bbs/topics/news/2005/NEW01175.html

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The Food and Drug Administration (FDA) today announced that Richard Pazdur, M.D., F.A.C.P. will lead its newly established Office of Oncology Drug Products within the Center for Drug Evaluation and Research (CDER). Dr. Pazdur is an experienced medical oncologist who has spent more than 20 years in leadership roles working on solutions to the complex issues in cancer drug development.

"Dr. Pazdur brings tremendous energy and innovative ideas to this very important position," said FDA's Dr. Steven Galson, Acting Director, CDER. "Dr. Pazdur's work will benefit cancer patients everywhere and reaffirm FDA's ongoing commitment to improving the efficiency and consistency of product development and review, so cancer patients will have access as quickly as possible to quality new treatments."

FDA recently announced the establishment of the Office of Oncology Drug Products to be housed in CDER. This office is a consolidation of three previous areas within CDER responsible for the oversight of drugs and therapeutic biologics associated with cancer treatment and prevention, including the Division of Oncology Drug Products that Dr. Pazdur currently heads. Additional areas of the Office's oversight will include the Division of Oncology Biologic Products and the Division of Medical Imaging and Hematology Drug Products. The Office will also develop and lead a comprehensive Oncology Program to facilitate coordination of oncology activities across all Centers of FDA, and ensure ongoing outreach and collaboration between FDA, the National Cancer Institute and other cancer-related organizations within and outside of the government.

"I am honored to have been selected from such a highly qualified group of applicants," said Dr. Pazdur. "I look forward to working with Acting Commissioner Crawford, Dr. Galson and the talented and dedicated scientists who will comprise the office to realize FDA's vision for it."

In announcing the appointment, Dr. Galson said Dr. Pazdur is uniquely qualified to lead FDA's efforts to provide for an even stronger and more consistent approach to the development and review process for therapeutic products used to diagnose, treat, and prevent cancer. Dr. Pazdur will continue to work closely with the cancer community to ensure that FDA has the most effective and efficient development and review processes possible to ensure the safety and effectiveness of life-saving and life-enhancing treatments for cancer patients.

Dr. Pazdur has a distinguished career in clinical and academic oncology, in addition to his experience as a regulatory expert at FDA. A native of Indiana, he obtained his M.D. from Loyola Stritch School of Medicine, where he also trained in Internal Medicine. He was a fellow in oncology at Rush Presbyterian-St. Luke's Medical Center and the University of Chicago. Dr. Pazdur has served as a practicing oncologist, researcher and teacher at Wayne State University and for many years at the M.D. Anderson Cancer Center at the University of Texas, where he was a tenured Professor of Medicine and Assistant Vice President for Academic Affairs.

Dr. Pazdur is well known in the oncology community as a strong scientific leader who is committed to the care and treatment of patients with cancer. He is a member of many oncology professional societies and has served on numerous local, state, national and international committees focused on cancer treatment, drug development, patient education and chemoprevention. Since coming to FDA, Dr. Pazdur has collaborated extensively with the leaders at the National Cancer Institute on many aspects of facilitating sound and rapid product development for cancer treatment and prevention.
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[mskatiescarletohara]

Dew....I beg to question....now that he's in charge, will he move to make his viewpoints on accelerated approval a statute?

katie...

[DewDiligence]

Pazdur in the news again:

[Editorial from Thursday’s WSJ.]

http://wsj.com

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The FDA vs. Cancer Patients
May 19, 2005
The American Society of Clinical Oncologists met this week in Florida, where it heard promising study results about a host of developmental cancer therapies. "Just in the last year or so there are many more options," one researcher was quoted as saying. "None of them are FDA-approved yet. Hopefully soon they will be."

The bad news is that "hopefully" really is the operative word here. Former FDA Commissioner Mark McClellan made some progress moving the agency to speed up the drug approval process. But he was pulled away to run Medicare, and agency bureaucrats have since been working feverishly to turn back the clock.

The latest evidence of backsliding was a recent vote of the Oncologic Drugs Advisory Committee (ODAC) to recommend against approving Johnson & Johnson's leukemia drug Zarnestra. The drug may not be a miracle cure -- 15% of study patients achieved complete remission. But 15% is nothing to sneeze at either, especially since the company was seeking accelerated approval for the treatment of elderly patients who might not be able to withstand the punishment of traditional chemotherapy. Yet ODAC voted against adding this weapon to the anti-cancer arsenal.

This is a special shame because ODAC used to be a bastion of common sense, wherein clinicians who treat cancer patients would often buck FDA statisticians to approve new drugs. But ODAC is now chaired by osteopath Silvana Martino, who is notably hostile to the drug industry, and so it is unlikely to continue to be an independent check on the FDA.

A related blow for cancer patients was the selection last month of Richard Pazdur to head the FDA's newly consolidated oncology drugs division. Drs. Pazdur and Martino share the view that the FDA's mission is to force the pharmaceutical industry to jump through certain hoops as much as it is to get good drugs to patients. "The purpose of accelerated approval was not accelerated drug company profits," Dr. Pazdur says, as if the researchers whose work is coming before him are selling snake oil.

Dr. Martino, meanwhile, believes that "millions and millions of dollars are being spent looking for drugs with low efficacy" [I agree with this assertion, FWIW]; she should tell that to patients for whom incremental progress can mean extended lives. The fear in the cancer patient community is that the doctors want to undo the accelerated approval process for all but the most obviously effective cancer drugs, even though many of the best ones only demonstrate their true worth when they are used in clinical settings.

This was demonstrated again at the oncologist meeting. Notable among the impressive drugs was Erbitux, whose original rejection by the FDA helped land Martha Stewart in jail, and which continues to look better and better as a treatment for colon cancer.

The next thing to watch for is the fate of AstraZeneca's lung-cancer drug Iressa, which Dr. Pazdur is signaling he may actually pull from the market as one of those "low efficacy" drugs. True, Iressa helps only about 10% of patients. But those who respond to it respond massively. "I've had patients who have gone from being on oxygen to skiing at altitude," says one doctor of the drug. Genetic tests are being developed to better predict who will respond to Iressa. Yet Dr. Pazdur seems to regard the FDA's Iressa approval in 2003 as an instance of the drug industry getting away with one. Incredible.

One way Congress could fight back would be with a law ending the moral travesty of placebo-controlled drug trials for terminal diseases. This has been Dr. Pazdur's main delaying tactic, justified as a way to prove efficacy beyond any doubt, regardless of how many people may die in the interim. (The oncologist conference also saw data presented questioning the value of lengthy drug trials.)

As for the White House, its failure to offer adult supervision of the FDA -- an executive branch agency that regulates one-quarter of the economy -- is increasingly notable and unfortunate. The agency has lacked a Commissioner confirmed by the Senate for about year; acting head Lester Crawford has been nominated for the job but is mired in the Senate's confirmation maw and in any case shows little inclination to buck the FDA culture that produced Dr. Pazdur.

Who would have thought that, five years into a Republican Administration, the FDA would be staffed by people who regard industry as an adversary, not a partner, in the anti-cancer fight.
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