Tag Archives: FDA approval

Covid-19: FDA set to grant full approval to Pfizer vaccine without public discussion of data

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Gareth Iacobucci, BMJ: August 20, 2021

Transparency advocates have criticised the US Food and Drug Administration’s (FDA) decision not to hold a formal advisory committee meeting to discuss Pfizer’s application for full approval of its covid-19 vaccine.

Last year the FDA said it was “committed to use an advisory committee composed of independent experts to ensure deliberations about authorisation or licensure are transparent for the public.”1 But in a statement, the FDA told The BMJ that it did not believe a meeting was necessary ahead of the expected granting of full approval.

“The FDA has held numerous meetings of its Vaccines and Related Biological Products Advisory Committee (VRBPAC) related to covid-19 vaccines, including a 22 October 20202 meeting to discuss, in general, the development, authorisation, and licensure of covid-19 vaccines,” an FDA spokesperson said.

“The FDA also has held meetings of the VRBPAC on all three covid-19 vaccines authorised for emergency use and does not believe a meeting is needed related to this biologics license application.”

The spokesperson added, “The Pfizer BioNTech covid-19 vaccine was discussed at the VRBPAC meeting on 10 December 2020.3 If the agency had any questions or concerns that required input from the advisory committee members we would have scheduled a meeting to discuss.”

The vaccine has already been rolled out to millions of Americans through an emergency use authorisation. Companies typically apply for full approval after a longer period has elapsed so that more data are available for review.

But with the US government indicating this week that it plans to start making booster shots widely available next month, experts said the decision not to meet to discuss the data was politically driven.

Data scrutiny

 Kim Witczak, a drug safety advocate who serves as a consumer representative on the FDA’s Psychopharmacologic Drugs Advisory Committee,4 said the decision removed an important mechanism for scrutinising the data.

“These public meetings are imperative in building trust and confidence especially when the vaccines came to market at lightning speed under emergency use authorisation,” she said. “The public deserves a transparent process, especially as the call for boosters and mandates are rapidly increasing. These meetings offer a platform where questions can be raised, problems tackled, and data scrutinised in advance of an approval.”

[….]

Public discussion

Diana Zuckerman, president of the National Center for Health Research, who has also spoken at recent VRBPAC meetings, told The BMJ, “It’s obvious that the FDA has no intention of hearing anyone else’s opinion. But if you make decisions behind closed doors it can feed into hesitancy. It’s important to have a public discussion about what kind of data are there and what the limitations are. As we think about risk versus benefit, we need to know.”

Joshua Sharfstein, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health and former FDA deputy commissioner during the Obama administration, said that advisory committee meetings were more than just a way of receiving scientific input from outside experts. “It’s also an opportunity to educate the public about the important work that the FDA has done reviewing an enormous amount of data about a product,” he told The BMJ. “It’s a chance for questions to be asked and answered, building public confidence. If there are no advisory committee meetings prior to licensure, the FDA should consider taking extra steps to explain the basis of its decisions to the public.”

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To read the entire article, click here https://www.bmj.com/content/374/bmj.n2086

Beleaguered FDA in talks for drug-company funding

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Eleanor Laise, Marketwatch: July 13, 2021

Amid a firestorm over its approval of a new Alzheimer’s treatment, the Food and Drug Administration is holding closed-door meetings with companies it regulates — talks that critics say allow drug and device makers to exert outsize influence over the agency’s operations, threatening to erode public trust in the agency at a critical moment.

The talks focus on “user fees” that pharmaceutical and medical-device companies pay to the FDA annually and when applying for approval of new products. The FDA in recent years has become increasingly reliant on such payments, which funded nearly half of the agency’s total spending in fiscal year 2020. In exchange for the fees, the FDA agrees to certain deadlines for reviewing new-product applications, the type and frequency of meetings with companies submitting applications, and other commitments. The medical-product user-fee agreements are generally renegotiated every five years — a process that’s happening now, in advance of the current agreements’ expiration next year — and submitted to Congress for authorization.

Although the FDA is required by law to consult with patient and consumer advocacy groups on the discussions and make minutes of its industry meetings public, the meat of the talks often remains hidden, observers say. Since September of last year, the FDA has held more than 150 meetings with industry to discuss fee agreements for brand-name prescription drugs, generics, medical devices and biosimilars (products similar to branded biologic drugs), which together are expected to generate nearly $2 billion for the agency this fiscal year. Yet consumer advocates and other outside groups attempting to track the discussions say they remain in the dark about most of the details. FDA summaries of some recent meetings have been posted months after the fact or sum up a discussion in a single sentence. Medical-product safety experts say they’ve repeatedly asked for more access and details on the negotiations, to no avail.

“We simply can’t get a view into this process, and the lack of transparency is deliberate,” says Madris Kinard, a former public health analyst at the FDA and CEO of Device Events, which tracks medical-device adverse-event reports.

Details about the negotiations that have trickled out raise alarms among some medical-product safety experts, academic researchers and consumer advocates that the industry’s leverage in these talks ultimately puts patients at risk. User fees are speeding more products to market without a corresponding increase in resources to track the safety of those products, critics say. Yet in the current round of negotiations, FDA efforts to allocate more user fees toward monitoring the safety of medical products already on the market have met industry resistance.

[….]

The main idea behind the user-fee programs was to speed up FDA review of medical-product marketing applications — and they’ve delivered on that front. The median time to approval for standard new-drug applications was 10 months in fiscal 2018. In the years before user fees were first enacted, the median FDA application review time was nearly three years, according to a study by Kesselheim and colleagues at Harvard and Brigham and Women’s Hospital.

[….]

But user-fee deadlines can have serious side effects, some experts say. As the opioid crisis was exploding, “there was a question of ‘Why does the FDA keep approving the opioids?’ ” says a former FDA official. “One reason was that they had applications and had user-fee obligations to review the applications.” So long as an application met the standard requirements, “it would be approved,” he says. “That’s an example of the mindset” created by the deadlines.

Several studies have linked faster drug-approval timelines to safety issues. A 2014 study in Health Affairs found that drugs approved after user fees were enacted were more likely to get new black-box warnings or be withdrawn from the market than drugs approved in the pre-user-fee era. Other studies have found that, compared with drugs approved at other times, drugs given the green light shortly before their user-fee deadlines were more likely to have subsequent safety issues.

[….]

In the current round of medical-device user-fee negotiations, one of the FDA’s goals is to improve device safety, including through increased funding for surveillance of devices already on the market, the agency says. That proposal met stiff resistance from the industry, according to outside groups that have received FDA briefings on the talks. At an April 7 negotiation meeting, the industry expressed the view that fees “should be solely for the premarket review process,” according to a summary posted by FDA. Medical-device trade group AdvaMed didn’t respond to requests for comment.

At the start of the prescription-drug user-fee negotiations, the FDA also emphasized its hope of improving the Sentinel Initiative, a system for assessing the safety of approved medical products. But a related proposal advanced by the FDA during the negotiations was shot down by the industry, a December meeting summary notes.  

[….]

Revolving doors

“There’s not a lot of friction between the industry and the agency” in prescription-drug user-fee negotiations, says a former FDA official. “The industry knows it’s getting good value.”

A sign of the amicable relations: One FDA official leading the current round of prescription-drug user-fee negotiations left the agency in April of this year, according to her LinkedIn profile, to become vice president of science and regulatory affairs at BIO — one of the industry groups she’d just been negotiating with. The former FDA official, Khushboo Sharma, participated in a user-fee negotiation meeting with BIO and other industry representatives as recently as Feb. 12, according to meeting summaries posted by the agency. “That is obviously an outrageous situation and clearly undermines the integrity” of the process, says Diana Zuckerman, president of the National Center for Health Research, a nonprofit think tank.

Asked for comment, the FDA sent a link to its post-employment restrictions, which say in part that current employees who have begun seeking employment outside the federal government must immediately recuse from certain matters that affect “the discrete industry, economic sector, or other defined class of organizations in which the prospective employer operates.” BIO didn’t respond to a request for comment. Sharma says that she worked with FDA ethics officials “to ensure I was recusing myself from all appropriate activities. I started seeking post-employment opportunities after negotiations had concluded.”

When the agency’s position does conflict with an industry’s, the FDA “is not going to come out on top,” says Lisa McGiffert, a patient-safety advocate at the nonprofit Patient Safety Action Network. Given the industry’s track record of snagging many items on its wish list, some observers are concerned that the current round of negotiations could chip away at FDA standards for approving new drugs. One issue: the use of “real-world data,” which can come from insurance claims, medical records, disease registries and other sources beyond the bounds of clinical trials. In an August 2020 letter to the FDA about user-fee reauthorization, PhRMA said that real-world data and evidence “may, in some circumstances, be adequate on their own to satisfy the substantial evidence criteria for demonstrating effectiveness” of drugs.

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To read the entire article, click here.

Emergency Use Authorization vs. Full Approval: What are the Implications?

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Laurie Saloman, Contagion Live: June 20, 2021

Emergency use authorizations, or EUAs, have gotten a lot of attention during the COVID-19 pandemic. The concept of the U.S. Food and Drug Association (FDA) authorizing a product or treatment quickly and without going through a full and complete review process was first introduced in 2005. At that time, the FDA issued an EUA for an anthrax vaccine available to military personnel due to a spate of anthrax-laced letters that killed or sickened nearly 2 dozen people.

Over the following years, EUAs were issued for a variety of experimental therapies for diseases such as H1N1 (swine flu), Middle East Respiratory Syndrome (MERS), Ebola, and Zika, which often arose quickly and threatened to become bona fide pandemics. Since last year, numerous EUAs have been issued for COVID-19-related products, including diagnostic and antibody tests, clinical treatments, and vaccines.

But what does it actually mean when a product is given an EUA, and why don’t companies automatically seek full FDA approval? According to Diana Zuckerman, PhD, president of the National Center for Health Research, there are several reasons why a company might not pursue approval for a product.

“One [reason] is that it’s found to not work, and so no effort is made to get it approved, and the other is that the company doesn’t necessarily have the incentive to do the research that they would need to do in order to get it approved, because the standards for an EUA are always lower than the standards would be for FDA approval,” she said. “If FDA approval would require a bigger, longer-term study with more patients, that just may not be worth it.” She offered the example of EUAs for various therapies for the Ebola virus, which does not currently present a threat to the US.

Even if a company wants to receive full approval for a product, it can run into problems if it can’t find enough of a patient population to participate in large-scale trials, added Susan Wood, PhD, professor of Health Policy and of Environmental and Occupational Health at the George Washington University Milken Institute School of Public Health and the former Assistant Commissioner for Women’s Health at the FDA.

Zuckerman and Wood agreed that, ideally, companies producing therapies that receive EUAs would go on to pursue approval for these therapies, especially as approved therapies can sometimes be repurposed to work for conditions other than those for which they were initially intended. “The reason why we were able to move…quickly with Covid was because of the work that had been done with other coronaviruses previously, and that really set the stage,” Zuckerman said. “Whether it’s for a rare disease or a future pandemic that we can’t predict, yes, having more information now can help us later.”

For companies, having full approval provides a measure of control. The FDA can withdraw an EUA at any time, preventing a company from selling or dispensing their product; in contrast, it can take several years for the agency to rescind an approval. Insurance typically doesn’t pay for products under an EUA, although in the case of Covid-19 vaccines the government is footing the bill, possibly making financial motives less of a factor for pharmaceutical companies.

But while EUAs are designed to help people get immediate assistance, it’s not uncommon for tests or therapies granted EUAs to end up being ineffective. In the case of COVID-19 tests and treatments, the FDA issued EUAs it later revoked. For example, in March of 2020, companies were permitted to sell antibody tests—which purported to tell users whether or not they had COVID-19 in the past—without submitting EUA applications. In May of 2020, companies were allowed to sell COVID-19 diagnostic tests for 15 business days before they had to submit EUA applications. During that month, the FDA issued 84 EUAs for various labs and companies, and there were an additional 400 applications pending review.

But by February of 2021, enough data on testing had been collected for the FDA to reject 225 different antibody tests. Similarly, although the FDA had granted EUA status to the drug hydroxychloroquine in March of 2020, by June of 2020 it was clear from studies that the drug not only had no discernible benefit but might even be harmful to Covid-19 patients, and the EUA was withdrawn in June 2020.

The lack of full approval by the FDA has been cited as a factor in the reluctance of some people to get the Covid-19 vaccine and has emerged as a flashpoint in the fight over vaccine mandates. Typically, mandates come after years of experience with a vaccine. “Normally…the testing is slower, the back and forth between the FDA and companies is slower, the review process is slower, and it comes on the market in a graduated fashion,” Wood said. At that point, there’s much more acceptance by the general population. “Now, everything’s been compressed, including EUA, and we’re moving straight into mandates by businesses.”

Read the original article here.

To Stay: Two More Cancer Indications With ‘Dangling Approvals’

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Kerry Dooley Young, Medscape News: April 29, 2021

Two more cancer indications that had been granted accelerated approval by the US Food and Drug Administration (FDA) are going to stay in place, at least for now. This was the verdict after the second day of a historic 3-day meeting (April 27–29) and follows a similar verdict from day one.

Federal advisers so far have supported the idea of maintaining conditional approvals of some cancer indications for a number of immunotherapy checkpoint inhibitors, despite poor results in studies that were meant to confirm the benefit of these medicines for certain patients.

On the second day (April 28) of the 3-day FDA meeting, the Oncologic Drugs Advisory Committee (ODAC) supported the views of pharmaceutical companies in two more cases of what top agency staff call “dangling accelerated approvals.”

ODAC voted 10-1 in favor of maintaining the indication for atezolizumab (Tecentriq) for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

ODAC also voted 5-3 that day in favor of maintaining accelerated approval for pembrolizumab (Keytruda) for first-line cisplatin- and carboplatin-ineligible patients with advanced/metastatic urothelial carcinoma.

The FDA often follows the advice of its panels, but it is not bound to do so. If the FDA were to decide to strip the indications in question from these PD-1 medicines, such decisions would not remove these drugs from the market. The three drugs have already been approved for a number of other cancer indications.

Off-label prescribing is not uncommon in oncology, but a loss of an approved indication would affect reimbursement for these medicines, Scot Ebbinghaus, MD, vice president of oncology clinical research at Merck & Co (the manufacturer of pembrolizumab), told ODAC members during a discussion.

[….]

Another participant at the meeting asked the panel and the FDA to consider the burden on patients in paying for medicines that have not yet been proven to be beneficial.

Diana Zuckerman, PhD, of the nonprofit National Center for Health Research, noted that the ODAC panel included physicians who see cancer patients.

“You’re used to trying different types of treatments in hopes that something will work,” she said. “Shouldn’t cancer patients be eligible for free treatment in clinical trials instead of paying for treatment that isn’t proven to work?”

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To read the entire article, see https://www.medscape.com/viewarticle/950165

Conflicts Galore: Upcoming Accelerated Approval Cancer Panel May Be Tainted By Industry Relationships

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Sarah Karlin-Smith, Pink Sheet: April 21, 2021

Six members of the FDA Oncologic Drugs Advisory Committee received conflict of interest waivers to participate in the agency’s upcoming three-day meeting to review the accelerated approval of six checkpoint inhibitor indications after the three cancer immunotherapies at issue failed to confirm clinical benefit in post-market trials raising questions about whether industry influence may heavily factor in the committee’s decision making.

The high number of waivers could mean that a majority or close to a majority of the panelists will have conflicts based on the typical number of advisors on FDA panels. The agency used to be subject to waiver limits but the 2012 FDA Safety and Innovation Act removed these restrictions.

ODAC’s 27-29 April meeting, part of the agency’s broader industry-wide effort to evaluate accelerated approvals for oncology drugs, is unprecedented in the number of drugs and indications up for accelerated approval withdrawal. The committee will discuss two indications for Tecentriq (atezolizumab); three for Keytruda (pembrolizumab); and one for Opdivo (nivolumab).

[….]

Vinay Prasad, a hematologist-oncologist at the University of California San Francisco acknowledged that it may not always be easy to find unconflicted experts but, he said they do exist. He also argued that in this case you might be able to look at other professionals like internists who study research methods and FDA approvals, for example for panel members.

[….]

Diana Zuckerman, president of the National Center for Health Research said that while FDA needs some people with clinical expertise who understand the illness and issues with the treatment, it doesn’t need an entire panel of these people. She said that one way FDA can find more qualified experts is by looking at schools of public health where academics rarely get money from industry and they have expertise in understanding clinical trials as well as biostatics.

Even if the academic’s salary isn’t directly funded by their work with industry, there are multiple reasons to be concerned that work on industry trials with the same drugs creates conflicts.

“There’s research showing that researchers feel more positively about drugs that they’ve studied. That’s normal human behavior. You feel proprietary towards something that you’ve studied. You also have a relationship with the company,” said Adrian Fugh-Berman a professor Pharmacology and Physiology at Georgetown where she directs PharmedOut, a project that focuses on evidence-based prescribing and studying industry marketing practices.

The person may also be thinking about how their behavior on the committee may impact other research opportunities the university or they in particular have with the company, she explained.

“Are you going to get more research grants for the company if you kill their drug?” Fugh-Berman said.

[….]

Over the past 12 months ODAC has had two other committee meetings where four waivers were granted but that is far from typical. Most agency advisory committees don’t have any waivers or at most have one or two, per data from FDA from 2018 onward.

FDA is supposed to publish an annual report to Congress on advisory committees that include information on waivers but the latest report available online was from fiscal year 2016. FDA did respond to questions about whether more updated data exists and where it can be found.

​To read the entire article, see https://pink.pharmaintelligence.informa.com/PS144196/Conflicts-Galore-Upcoming-Accelerated-Approval-Cancer-Panel-Includes-Many-Industry-Relationships

FDA blasts Merck’s Keytruda data for new breast cancer indication

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Ed Silverman, Stat News: February 5, 2021

Merck (MRK5 ) may have readily turned its Keytruda cancer drug into a medical and financial juggernaut, but its bid to win regulatory approval for at least one additional use may not come so easily, judging by documents from the Food and Drug Administration. The drug maker wants to sell the medicine to combat high-risk, early-stage triple-negative breast cancer along with chemotherapy before surgery, and then by itself after surgery.

[…]

Given the FDA review, though, the likelihood of a recommendation next week is not high, according to Ira Loss of Washington Analysis, who tracks pharmaceutical regulatory and legislative matters for investors. “The agency believes, and we think the (FDA expert) committee will agree, that further data from the trial are needed to make an informed decision,” he wrote to investors.

Another FDA watcher was even more blunt. “It’s important to have good treatment because this disproportionately occurs among Black women,” said Diana Zuckerman, who heads the National Center for Health Research, a nonprofit think tank. “But they’re saying this may not be needed, may not work and may be harmful – that’s pretty damning. And there are some real safety issues that can have terrible impact on patients… This is one of the most negative reviews I’ve ever seen.”

[….]

Read the full article here