Senators Grill Price, but He Stands His Ground

MedPage Today

Jan. 18, 2017
WASHINGTON — Repeal of the Affordable Care Act and its consequences were on the hot seat as senators questioned Rep. Tom Price, MD (R-Ga.) Wednesday about his fitness to serve as Secretary of Health and Human Services.

“I have serious concerns about your qualifications for the department you hope to lead,” said Sen. Patty Murray (D-Wash.), ranking member of the Health, Education, Labor, & Pensions (HELP) Committee, at a hearing on the nomination. “Just last week you voted to begin the process of ripping apart our healthcare system without any plan to replace it, even though [it’s estimated that] 30 million people will lose their coverage.”

Wednesday’s hearing was a “courtesy” hearing before the committee, which is not tasked with sending Price’s nomination to the Senate floor for a vote. That responsibility falls to the Senate Finance Committee, which is scheduled to hold a formal confirmation hearing and vote on the Price nomination next Tuesday.

Healthcare for All

Price maintained that if he is confirmed, he will fulfill president-elect Donald Trump’s promise of healthcare for everyone. “The principles that I think are absolutely imperative for the healthcare system is one that’s affordable for everybody, one that provides access to health coverage and care for everybody, one that’s of highest quality, that’s responsive to patients … one that incentivizes innovation, and that insures choices are made and preserved by patients,” he said.

Access was a word that Price returned to frequently when he was asked if he would guarantee that certain groups would not lose healthcare coverage under a replacement for the ACA. “It’s incredibly important that we have a system for every single American to have access to the kind of coverage they need and desire,” he said in answer to another question.

Access to health insurance is not an exact match for President-elect Donald J. Trump’s promise of health insurance for all, a point hammered home by Vermont Sen. Bernie Sanders, the independent who challenged Hillary Clinton for the Democratic nomination. “I have access to buying a $10 million home. I don’t have the money to do that,” Sanders said.

Democratic senators also pressed Price on potential conflicts of interest, specifically his healthcare stock trades, several of which been the subject of media coverage. Price maintained that many of his stock trades are done through a broker so he is not always aware of them, and that he has disclosed any relevant trades as required by the House Office of Government Ethics.

In response to questions about his purchase of stock in six pharmaceutical companies shortly before introducing a bill blocking a regulation that would likely have hurt those same companies, he noted that “My opposition to having the federal government dictate what drugs are available to patients is longstanding.”

Contraception Coverage

Murray also asked Price about his views on paying for contraceptive coverage. “You have said you don’t think cost is an issue for women in buying birth control and stated, ‘Bring me one woman who has been left behind … there is not one,’ correct?” she said.

“I think what I said and what I meant was that when I had patients in my office who were unable to afford medication, we did everything we could to make certain they got that medication. What I meant to capture in that conversation was that if there are individuals who are unable to afford that med, or any med, that there are avenues within the healthcare system physicians and others take to make sure individuals receive medication that they need.”

Murray related the example of a constituent diagnosed with endometriosis who takes contraceptives for chronic pain and who told Murray that “No copay birth control is an essential tool for helping women like me with endometriosis who otherwise would have to live with chronic pain.”

“Women are deeply concerned about the impact this election could have on access to healthcare they need; I’ve heard from many of them,” said Murray. “Will you commit to ensuring all 18 FDA-approved methods of contraception continue to be covered so women don’t have to go back to paying extra costs for birth control?”

“What I will commit to … is that we believe strongly that every single American ought to have access to the kind of coverage and care they desire and want,” said Price. “That’s our commitment and it runs across the board.”

“Birth control is an essential part of women’s healthcare and if you are confirmed I will be holding you accountable for that,” Murray responded.

As was expected, Price received friendlier queries from Republicans on the HELP Committee. “You are clearly one of premier people in all of Congress to understand the problems of healthcare, and have the background … to solve the problems we have,” Sen. Orrin Hatch (R-Utah) said to Price, an orthopedic surgeon.

Sen. Rand Paul, MD (R-Ky.), also spoke favorably of Price. “I think what I regret about this kind of hearing is sort of the vitriol, the rancor and partisanship that should go into something; we want the same things. To question your motives is insulting; To question whether you’re honest is insulting … I think we all want the most amount of insurance for people, and the least amount of cost.”

Paul and Price discussed ideas that might be included in a Republican replacement for the ACA, including health savings accounts and high-deductible catastrophic coverage. “I think health savings accounts and high-deductible catastrophic coverage make a whole lot of sense for many individuals; they ought to have the choice,” said Price.

He also said a replacement plan could include high-risk pools to insure people who might otherwise have trouble getting coverage. Sen. Al Franken (D-Minn.) who was called on next to question Price had his own comment on the risk pool idea: “I’ll tell you how to get a really big risk pool — it’s called Medicare for everyone,” he said.

Price also discussed the Meaningful Use regulations for physicians’ use of electronic health records. “Electronic medical records and electronic health records (EHRs) are so important because … they allow the patient the opportunity to have their health history with them at all times, and allow the provider access to that,” he said. “We in the federal government have a role [in EHRs], but that role ought to be interoperability, to make certain that different systems can talk to each other so it inures to the benefit of the patient.”

But the Meaningful Use rules have really been burdensome for doctors, Price added. “I have had more than one physician tell me that the final regulations and rules related to Meaningful Use were the final straw for them … and they quit.”

“I think the thing that’s absolutely imperative, is to find out what things ought to be determined and checked … that the metrics used actually correlate with what’s being provided … so if we truly worked with those providing the care, saying, ‘What is it that we could ask you to measure that would really correlate with the outcome and quality of care provided,’ I suspect there’s some really specific things we could use.”

“Hope those watching are reassured by what they heard from you,” committee chairman Sen. Lamar Alexander (R-Tenn.) said as the hearing concluded. “While we intend to repair damage from Obamacare and that would mean repealing major parts of it, that won’t become effective until alternatives are in place … we don’t want to pull the rug out from everybody.”

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Volunteers deliver petitions to the Senate HELP Committee with more than 510,000 signatures from people opposing the nomination of Rep. Tom Price, MD, as Health and Human Services secretary. (Photo by Shannon Firth)

Voices Opposed

Just before the hearing began Wednesday morning, representatives of Planned Parenthood, the National Physicians Alliance, Physicians for a National Health Program, and Public Citizen, hand-delivered stacks of boxes containing various anti-Price petitions that they report include 500,000 signatures.

“As a physician, it just doesn’t look like he puts the interests of patients first,” said Susan Molchan, MD, a psychiatrist, nuclear medicine physician, and member of the board of directors for the National Physicians Alliance, told MedPage Today.

Molchan cited his stock buys in tobacco companies as evidence that Price has put corporate interests ahead of patients. Price opposed regulating nicotine as a drug, but Molchan said “nicotine has clearly been accepted as a drug, a very addictive drug for years.”

Price’s support for privatizing Medicare, by transitioning to a voucher-like program for future beneficiaries, also worried Molchan.

“To throw Medicare, which has much lower overhead than private insurance … into the grinder of private health would be terrible.” While she acknowledged that Medicare has its flaws, “it works better than the private health industry, which is out for big corporate entities,” she said.

If his nomination is confirmed, Price’s leadership, “will further erode standards for the approval of medical devices and the approval of drugs,” said Sammy Almashat, MD, MPH a research associate for Public Citizen’s Health Research Group based here.

“We’re very concerned that his presence [at HHS] will send a message to the FDA that the standards should be lowered even further than they already have been.”

His support for repealing the Affordable Care makes him “very dangerous” particularly for Americans with life-threatening diseases such as cancer and HIV and other chronic diseases, he said.

“[G]utting the minimal safety nets that still exist in the form of Medicare, in the form of the Affordable Care Act, would be disastrous for those patients. As a physician, I don’t see how another physician could support such policies.”

What Else is in the 21st Century Cures Act?

WASHINGTON — When most people think about the 21st Century Cures Act, they think about curing cancer and Alzheimer’s disease, and curbing the nation’s opioid epidemic. But the nearly 1,000-page healthcare spending bill, which President Obama signed in mid-December, also aims to reform the nation’s fragmented mental health system, improve access to electronic health data, and ensure that underrepresented individuals are included in important health research.

Mental Health

Approximately 13 million people in the U.S. have a serious mental illness or substance use disorder, according to the American Psychiatric Association (APA), which applauded the 21st Century Cures Act, calling its reforms to mental health a “huge step forward.”

The Cures Act included efforts to promote evidence-based treatments, strengthen mental health parity, and bolster the mental health workforce. The bill also established a grant program focused on early intervention for those showing warning signs of a potentially serious mental illness.

Earlier this year, Congress took aim at the Substance Abuse and Mental Health Services Administration (SAMHSA), saying that the agency had failed patients with serious mental health problems.

One almost immediate change the bill makes is to establish a new assistant secretary for Mental Health and Substance Abuse to oversee SAMHSA, explained Andrew Sperling, director of legislative advocacy for the National Alliance on Mental Illness.

Speaking in a phone interview with MedPage Today that included a public relations official, Sperling said he anticipates that Rep. Tom Price (R- Ga. ), the newly appointed Secretary of Health and Human Services, will have “a great deal of influence” in selecting that individual.

Better Integration, Better Care

The 21st Century Cures Act also designates a new Interdepartmental Serious Mental Illness Coordinating Committee, charged with summarizing advances in diagnosing and treating serious mental illness in a written report to congress. The committee — which includes members from SAMHSA, the Department of Defense, the Health Resources and Services Administration (HRSA), and other federal health agencies — will also be required to evaluate the impact of federal programs on important public health outcomes (i.e., rates of suicide, preventable emergency room visits, and homelessness).

Other key mental health-related provisions of the bill include the following:

  • Authorizing a grant program for assertive community treatment for adults with serious mental illness;
  • Authorizing a grant program to enable local governments to improve crisis intervention among emergency responders, clinicians, and law enforcement and funding to build registries of available inpatient psychiatric beds;
  • Establishing policies to create new residency programs to train future primary care doctors and psychiatrists about integrating mental and physical health;
  • Designating a nationwide hotline and online tool for improving access to mental health and substance use providers; and
  • Enhancing grant programs that offer behavioral health services for homeless and justice-involved individuals.

Also, the Cures Act, while not amending the Health Insurance Portability and Accountability Act (HIPAA), does outline the circumstances by which clinicians can share information with family members when a loved one is in crisis. “We hope this will ease the chilling environment around disclosure of information to family members,” by providing clinicians with greater clarity regarding when they can disclose, Sperling said.

With regard to mental health parity — equal access and coverage from insurers for mental health issues compared with physical concerns — most states have not been aggressively auditing insurers, an APA representative told MedPage Today.

However, the Cures Act calls for a standardized approach to auditing, and, on a federal level, requires the Department of Labor to periodically publish reports to showcase the volume of cases the agency has pursued.

Efforts to ensure more consistency and transparency could produce a “sentinel effect,” said the APA official. The more that insurers believe they risk being audited, the more likely they are to take internal compliance seriously.

Electronic Health Records

The Cures Act also strengthens efforts to improve and enforce health information interoperability.

Beginning in January 2018, vendors’ relative interoperability will be evaluated, and by 2019, those not in compliance will lose certification, explained Mandy Long, chair of the Electronic Health Records Association (EHRA) Clinician Experience Workgroup for the Healthcare Information and Management Systems Society (HIMSS), speaking in a phone interview with MedPage Today during which a public relations official was present.

“There are real teeth to [the language in the bill], and [the penalties] grow over the course of a couple of years,” said Long, who is also vice president of product management at Modernizing Medicine, an EHR and practice management software company in Boca Raton, Fla.

She noted that vendors who engage in data blocking can be fined up to $1 million per violation.

Long, whose daughter has Turner syndrome, also spoke as the parent of an ill child about the challenge of keeping specialists in different hospitals current with her daughter’s health status and tests. “We call it the ‘patient’s Bible’ — that binder that patients create for themselves, or their parents create [of various medical records] — we lug it from visit to visit or, God forbid, if we end up in an emergency situation; it’s awful and frequently out of date.”

Long said she believes the bill’s requirements to promote a scalable integration structure will have benefits for patients as well as industry.

The College of Healthcare Information Management Executives (CHIME) offers more specifics on the health IT provisions of the bill related to information blocking, interoperability standards, and hardship exemptions for decertified EHRs.

Superbugs, Vaccinations, and Equity in Research

Other elements of the bill include provisions to fight superbug infections, such as allowing the FDA to require manufacturers or reusable medical devices to share their cleaning instructions and verify that such methods work. The Cures Act also creates new requirements for the National Institutes of Health to encourage scientists studying similar topics to collaborate, with the goal of increasing the volume of data on underrepresented populations (i.e., women, children, and minorities).

Finally, the bill aims to raise maternal vaccination rates through efforts to prevent vaccine shortages and by incentivizing drugmakers to develop new vaccines for pregnant women. In addition, the act encourages pediatric drug development by allowing products given a “rare pediatric disease designation” from the FDA before 2020 the chance to be considered for a voucher until 2022.

Eteplirsen Approval Seen as Marking New Direction at FDA

On April 26, an FDA advisory committee voted 7-6 that the exon-skipping drug eteplirsen for Duchenne muscular dystrophy (DMD) failed to meet the standards needed for accelerated approval. It was widely assumed that the FDA would tell the drug’s developer, Sarepta Therapeutics, to try again with better data. That, of course, did not happen. In this follow-up, we report on how it eventually did turn out for the drug and for the DMD community.

To the surprise of many, the FDA approved eteplirsen in September with the trade name Exondys 51.

While patients and families applauded the decision, believing their efforts in collaborating with industry and the agency had paid off, critics in the medical and research community questioned whether the drug really worked, and whether the FDA had made the right call. Documents later revealed internal FDA friction, and even though the agency’s boss backed the approval, he also called for a key study supporting the drug to be retracted.

In addition, two recent events — passage of the 21st Century Cures Act, a major health bill meant to spur innovation and speed the delivery of new drugs, and the surprise election of Donald Trump as president — have sparked concerns that the FDA might inch closer to deregulation for the sake of innovation under the new administration.

Perhaps more than in previous White House transitions, confusion and uncertainty cloud the FDA’s future.

Yet while consumer groups express alarm, some clinicians and policy experts believe a dramatic reversal in the FDA’s core mission is unlikely. MedPage Today spoke with key stakeholders to gauge the importance of eteplirsen’s approval: what it means for patients and the future of the FDA’s review process.

Flash Point

In approving eteplirsen, the FDA had overruled its own advisory committee. The seven members voting against approval did not believe Sarepta had shown adequate evidence that eteplirsen triggered production of the protein dystrophin at a level that was “reasonably likely to predict clinical benefit.” (DMD is caused by a genetic deficiency in dystrophin.)

Moreover, several of the FDA’s senior staff members also saw evidence that patient benefit was inadequate, as documents detailing a months-long dispute between those staff members and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research (CDER), showed. She overruled their conclusions and FDA Commissioner Robert Califf, MD, ultimately sided with Woodcock. Curiously, however, Califf also called for the retraction of a 2013 study that aimed to demonstrate that eteplirsen produces adequate levels of dystrophin, which he called “misleading.”

Insurers also appear to need more convincing that the drug is effective. The investment firm Jefferies found that three of five national payers and eight of 15 regional managed care organizations “denied or restricted coverage for the drug,” according to Gena Wang, PhD, CFA, an analyst for Jefferies. Wang told Endpoints News, a biopharma newsletter, the response was “in line with our expectation of pushback from private payers.”

Unlike private insurers, public payers such as Medicaid do not have the option to omit FDA approved drugs from their formularies.

The ripple effect of the eteplirsen decision could prove damaging to the healthcare system, Diana Zuckerman, PhD, president of the National Center for Health Research, told MedPage Today.“Many drug companies will be submitting applications that they wouldn’t have dreamed of submitting [before].”

Zuckerman said Woodcock’s decision stemmed from sympathy for the patients.

“She approved a drug not realizing that by approving the drug based on evidence that was so obviously inadequate many health insurance companies would just refuse to pay for it.”

Without insurance coverage, families have to pay $300,000 a year for the drug. “The company failed in its responsibility, the FDA failed in its responsibilities, and the patients are paying the price,” Zuckerman said.

If the agency continues to move in this direction, insurers will spend more money to perform their own analyses of product data. Money that could have been better spent on coverage, she added.

On the issue of coverage determinations, Annie Kennedy, senior vice president of legislation and public policy at the Parent Project Muscular Dystrophy (PPMD), said some insurers’ refusals stemmed from a misunderstanding about the burden of the disease. Only about 2,000 U.S. patients have the specific genetic mutation making them potentially eligible for treatment.

PPMD has also pressed insurers offering narrow coverage determinations, arguing that even non-ambulatory patients can benefit from the drug. Kennedy and others have been sharing additional pulmonary data demonstrating “stability” on functional tests in treated participants compared to “a steady decline observed in the DMD natural history,” according to Sarepta documents.

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Kennedy anticipates that some insurers will revise their coverage determinations based on engagement with the community.

Looking Ahead

One of the FDA’s advisory committee members who voted against approving eteplirsen, Aaron Kesselheim, MD, JD, of Harvard Medical School/Brigham and Women’s Hospital in Boston, told MedPage Today that one of the challenges of that meeting was balancing the inconsistencies in the testimony he heard from patients and families with the data.

“How do we make sure that the patient voice is taken seriously, but at the same time also take the science seriously and come to an adequate final decision?” he said.

The newly passed “Cures Act” also has provisions that could affect the FDA’s review process. It allows the agency to use “real world evidence” in deciding whether to approve expanded indications for already marketed drugs.

If Cures is given “maximum flexibility” and FDA leadership has a deregulatory agenda, said Kesselheim,”I think the future will hold a lot more products like eteplirsen that are approved on the basis of a marginal effect on a surrogate measure that does not have a clear connection to clinical endpoints.”

“That’s going to put a lot of pressure on physicians trying to make the decisions whether or not to use the product [and] patients deciding whether or not to take the risk … in this context of insufficient information,” he added.

Trump’s election also brings the likelihood of new leadership at the FDA. Although he has made no announcement about replacing Califf as commissioner, most of his other appointees have been staunchly anti-regulation and many are coming from industry.

The possible change in agency leadership and the Cures Act together could allow the FDA to reconsider the balance between innovation and ensuring appropriate levels of safety and efficacy, said Caleb Alexander, MD, of the Johns Hopkins Bloomberg School of Public Health in a phone interview. Alexander chaired the FDA committee that voted on eteplirsen.

However, given the massive size of the FDA, whatever change does occur will be gradual, he said. “I’ll be surprised if it’s a total sea change.”

“While cases such as Addyi (flibanserin) and eteplirsen have been quite controversial, those represent a small fraction of the reviews that FDA has performed … I don’t think that those cases are reflective of wholesale change or any deliberate decisions … regarding a change in the evidentiary threshold for market access.”

As for the worry that the “Cures Act” could encourage the use of more real world evidence, Alexander saw no conflict between leveraging patient reported outcomes, for example, and high quality science.

He added, “There’s a reason the FDA has evolved toward the use of randomized controlled trials, and frankly I don’t see that reliance diminishing substantially anytime soon.”

Advocates Respond

In response to the backlash against the FDA’s decisions and scorching criticism of Sarepta’s own clinical trial, Kennedy explained that the community was “flying the plane as we were building it.” For example, meetings focused on developing guidance for a protocol regarding how best to measure dystrophin happened as Sarepta’s own research was already underway.

“I know there’s been a lot of blame cast at this cast of characters or that cast of characters and a 152-page document released about disagreements,” said Kennedy referencing the FDA’s summary review.

But, she noted, “What we think happened was exactly what accelerated approval was designed for … All of these policies and tools that so many people have pushed for, for so long … were applied by everyone collaboratively and now we’ll get to see how this plays out going forward.”

“Now the onus is on Sarepta to conduct further studies to show [clinically meaningful benefit], that continues to happen in the broader subset of the community. If we don’t, then the product will get pulled,” she said.

Still the Watchdog

The FDA, in an emailed statement, underscored that its commitment to holding drug manufacturers, including Sarepta, accountable for confirmatory studies to determine clinical benefit will continue.

“The required study is designed to assess whether eteplirsen improves motor function of DMD patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval,” wrote Sandy Walsh, a press officer for the FDA in an email.

As for the future direction of agency, Walsh noted, “In appropriate situations, the agency exercises flexibility when evaluating treatments for serious and life-threatening conditions. However, as each situation is unique, we cannot speculate on potential decisions on other product applications.”

Senate Passes 21st Century Cures Act

WASHINGTON — The Senate passed the 21st Century Cures Act, sweeping legislation that aims to bring treatments more quickly from the lab bench to patients’ bedsides on Wednesday afternoon in a vote of 94-5.

“As a result of a lot of strong bipartisan work, we are sending a bill now to the president’s desk that will invest in tackling our hardest to treat diseases, put real dollars behind the fight against the opioid epidemic and make badly needed changes to mental health care in our country,” said Sen. Patty Murray (D- Wash.), Ranking Member of the Senate Health, Education, Labor and Pensions (HELP) Committee, just before the vote.

“I’ve heard often from those whose loved ones are suffering from Alzheimer’s, addiction, and other debilitating diseases,” wrote President Obama in a press release shortly after the vote, citing Vice President Joe Biden’s own tragic loss of his son Beau Biden.

“Their heartbreak is real, and so we have a responsibility to respond with real solutions,” Obama wrote, adding that he looked forward to signing Cures as soon as it reaches his desk.

The “Cures” bill authorizes a total of $6.3 billion for funding basic science, streamlining the FDA’s review process, and addressing the opioids epidemic. The bill also incorporates a handful of mental health reforms, aimed at improving care coordination, strengthening mental health parity laws, and promoting evidence-based treatments and therapies.

Murray thanked HELP Committee Chairman Lamar Alexander (R-Tenn.), who offered his own appreciation to his colleague and to those on both sides of the aisle.

Earlier this week Alexander called the bill’s provisions to invest in regenerative medicines “a game-changer” for stroke patients, those with heart disease or retinal disease and dubbed the entire package “another Christmas miracle” — referencing President Obama’s nickname for the 2015 rewrite of the “No Child Left Behind” education bill.

But not everyone was cheering: Public Citizen called the bill an early Christmas present for the pharmaceutical industry.

But the watchdog group didn’t sound only sour notes: in a prepared statement Michael Carome, MD, director of the group’s health research arm, claimed credit for helping to eliminate “provisions that would have 1) opened a gaping hole in the Physician Payments Sunshine Act for educational gifts made by industry to physicians; 2) increased medication prices and cost taxpayers an estimated $12 billion over 10 years; 3) encouraged hospitals to overuse the newest antibiotics, thereby contributing to the harmful spread of antibiotic resistance; and 4) allowed medical device manufacturers to make changes to high-risk medical devices without U.S. Food and Drug Administration oversight.”

Battling Opioids

Several Senators focused on the bill’s response to the opioids epidemic, emphasizing the current lack of resources and the slim capacity of many treatment facilities.

“When people with substance use disorder are turned away this means they remain on the streets, desperate, often committing crimes to support their addiction and at constant risk of a lethal overdose … Make no mistake this legislation will save lives,” said Sen. Jeanne Shaheen (D- N.H.) speaking from the floor on Tuesday.

Her colleague, Sen. Harry Reid (D- Nev.) said that the bill was “weak” in parts and “we could have done better,” but was also excited to see dollars for opioids.

“There should be far more, and it should be given a different way than we have it here, but it’s money,” he said. “And we have people … dying as a result of this scourge that’s sweeping America … So, that part of [the bill] is excellent.”

But the harshest critics of “Cures,”as the bill has been dubbed were unmoved by this sentiment.

Those opposing the bill included Sen. Bernie Sanders (I- Vt.), Sen. Jeff Merkley (D- Ore.), Sen. Ron Wyden (D- Ore.), Sen. Elizabeth Warren (D- Mass.), and Sen. Mike Lee (R- Utah)

The final breakdown for the bill is as follows:

  • $4.8 billion for the National Institutes of Health
  • $1 billion in state grants to help respond to the opioid crisis
  • $500 million in additional support for the FDA

Of the money allocated to the NIH over a 10-year period, the bill earmarks $1.8 billion for Vice President Joe Biden’s “Cancer Moonshot” project, — renamed “The Beau Biden Cancer Moonshot” — $1.6 billion for the BRAIN initiative, and $1.4 billion for President Obama’s Precision Medicine Initiative.

The Beau Biden Cancer Moonshot

The FDA’s funding would be geared towards bolstering research and staff, and like its sister agency, funds would be delivered over a decade, whereas the opioid grants will be administered over 2 years.

As Biden presided over a vote for cloture on Monday night, Congress offered an amendment to rename the Cancer Moonshot Initiative in memory of his son, Joseph “Beau” Biden III, who died from brain cancer in 2015.

“I think it fitting to dedicate this bill’s critical cancer initiatives in honor of someone who’d be so proud of the presiding officer [Biden] today: his son Beau,” said Senate Majority Leader Mitch McConnell (R-Kentucky).

That amendment passed without debate.

Winners and Losers

However, a second proposed amendment brought by Sen. Bernie Sanders (I -Vt.) did, receive pushback.

“I have been fighting the greed of the prescription drug industry for decades and as far as I can tell the pharmaceutical industry always wins. They win but the American people lose,” he said in a floor speech on Tuesday.

His legislation would allow Medicare to negotiate with drug companies and that would enable Americans to import their medications from other countries. Sanders stressed that both provisions had been endorsed by President-elect Trump during his campaign.

“Think about what you can do to pave the way for Mr. Trump coming in,” he said attempting to bait Senate Republicans who did not bite.

Full Speed Ahead

“One way to be sure and not get the work done we’re doing today is to add another topic,” said Sen. Roy Blunt (R- Missouri) who objected to Sanders’s amendment. “If everything’s a priority, nothing’s a priority.”

Sanders also criticized Cures for cutting $1 billion from Medicare and Medicaid programs and another $3.5 billion from the Affordable Care Act’s Prevention and Public Health Fund and for not giving enough funding to the NIH. Sanders said that if the bill passed it would still only grant the agency $7 billion less than it received in 2004, accounting for inflation.

The depletion of the ACA’s controversial fund also irritated the American Academy of Family Physicians, the group sent a letter to House leadership last week highlighting its disappointment, according to a press statement. The AAFP also noted that “the legislation stops well short of appropriately funding the important mental health and addiction provisions that are included.”

Mental Health

Echoing, Murray, Sen. John Cornyn (R-Texas) praised the bill’s mental health provisions noting that many families struggle to help their adult children who have mental health problems.

“Often there’s additional tools that need to be available to family members when they find that their loved one is getting sicker and sicker and not being compliant with their medication and potentially becoming a danger to themselves or to the community at large,” he said speaking from the Senate floor.

Cornyn noted that legislation will improve states and local government’s access to tools to help evaluate the healthcare needs of those in prison, so they can be helped. The bill also encourages the development of crisis intervention teams.

Though she voted for the bill, Sen. Debbie Stabenow (D- Mich.) urged Congress to “complete the job,” by delivering full-funding to community mental health centers.

The American Psychiatric Association applauded Cures saying it would improve the access and quality of care for people with serious mental illness, and those with substance use disorders.

“The bill will toughen enforcement of existing parity laws, helping to ensure that mental health care services are covered just like other health care services,” said Maria Oquendo, MD, PhD, president of the APA in a press release.

While Murray argued that another advantage of passing Cures now is to “lock-in” important investments ahead of the next administration, much of the actual funding in the bill will require Congress to appropriate or unlock dollars from various sources each year, such as sales from the federal Strategic Petroleum Reserve.

Approximately 420 organizations lobbied for the Cures bill, according to the The Center for Responsive Politics, including Blue Cross/Blue Shield, Roche, Amgen, and the Pharmaceutical Research & Manufacturers of America, the industry’s major trade association.

FDA Officials, Advisors Split Over New DMD Therapy

WASHINGTON — The FDA approved the first-ever drug for Duchenne muscular dystrophy (DMD), despite internal disagreements over the drug’s efficacy.

Eteplirsen (Exondys 51), a product of Sarepta Therapeutics of Cambridge, Mass., won approval from the agency — despite a split vote from its own advisory committee — to treat DMD patients who have a “confirmed mutation of the dystrophin gene amenable to exon 51 skipping” on Monday.

The FDA said it granted accelerated approval of the drug based on the surrogate endpoint of an increase in dystrophin production. However, its press statement failed to acknowledge the breadth of internal discord over this very point.

Following a conference call with investors Monday, Sarepta said that it anticipates charging $300,000 per patient per year for the new drug, according to Forbes.

‘The Principal Question’

The agency’s summary review chronicles a months-long dispute among senior staff and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research (CDER) over what FDA Commissioner Robert Califf, MD, dubbed the “principal question — whether the quantity of dystrophin produced by eteplirsen is an effect that is reasonably likely to predict clinical benefit,” as required by FDA statute and regulation.

Woodcock said she believes that clinical benefit is predicted, but Ellis Unger, MD, office director of the CDER’s Office of New Drugs (OND) disagreed. Back in April, seven of 13 members of the Peripheral and Central Nervous System Drugs Advisory Committee also said they felt eteplirsen failed to meet the minimum standards for accelerated approval.

In a 27-page July appeal letter to the Office of Scientific Integrity, Unger noted that members of the review team for Division of Neurology Products unanimously concluded that the new drug application should receive a “complete response action” (i.e. a rejection) and that OND director John Jenkins, MD, also verbally supported that decision (Ronald Farkas, MD, PhD, a lead reviewer in the neurology products division who was highly critical of eteplirsen data has already left the agency, according to STAT).

In his appeal letter, Unger argued that the small increase in dystrophin shown in the trials was not “reasonably likely” to predict clinical benefit, and that the effect size of dystrophin levels was “inadequate on its face.”

He noted that methods for quantifying dystrophin in the field are not standardized. Nevertheless, it was not valid to compare an increase in”Becker-type dystrophin” with dystrophin levels cited in other mutation or patient populations measured at other laboratories. Becker muscular dystrophy is a milder form of muscular dystrophy in which a truncated version of dystrophin is produced by muscle cells.

That said, if such a comparison were possible, Unger continued, “the largest change reliably demonstrated in Study 301 [a study comparing pre and post-treatment values of dystrophin after 48 weeks] of 1.3% is an order of magnitude less that the minimum dystrophin levels cited to be important in affecting the course of patients with Becker muscular dystrophy (at least 10%).”

Califf Defers

After Unger’s appeal, Califf was called on by the Scientific Dispute Process Review board to either conduct his own scientific review of the data, or to direct a panel of experts to make a recommendation on the current data, and if it meets the standard for accelerated approval.

Califf chose to conduct his own review and ultimately deferred to Woodcock’s “judgment and authority.”

“Given that I do not have technical expertise beyond those already involved in this decision and the record contains adequate evidence to support her conclusion, I defer to the judgment of the Center Director to approve eteplirsen under accelerated approval,” he stated in a letter.

He also responded to a series of concerns over Woodcock’s actions, with regard to the drug:

  • Her “intense involvement”at the early stages of the review process for the drug
  • Her “extensive involvement” in planning and engaging in the April 25, 2016 advisory committee meeting
  • Her “initial decision” to approval eteplirsen on May 4, 2016, before the reviewers had even established a decision-making process
  • Her completion of a final decisional memorandum before Unger completed his own

At the core of such complaints was an underlying assumption of bias towards Sarepta, and the patient community, which Califf said he acknowledged.

“Overall, while I recognize the strain created by political and public pressures, given Dr. Woodcock’s well documented history of not bowing to such influences and a record in this case showing her close consideration of all relevant scientific evidence, I do not find that this deviated from her responsibility as Center Director, nor do I find that she succumbed to pressure from the patient community, the public, the press, or others.”

Califf defended Woodcock saying her “hands-on” management style has been a characteristic of her career thus far, and was not related to eteplirsen specifically. He said he acknowledged that her “general pattern of discourse and involvement” was not “typical,” but affirmed that he did not “find that her conduct was in conflict with the job requirements for Center Directors at the FDA.”

A Complex Process

MedPage Today spoke with two members of the advisory committee about the FDA’s final decision, which went against their recommendation.

The process of approving a drug is very complex, said Aaron Kesselheim, MD, JD, MPH, of Brigham and Women’s Hospital in Boston, and a temporary advisory committee member who voted against approving eteplirsen. “As an advisory committee member, you are only involved in one small slice of the decision-making process.”

Kesselheim said that he could not say whether the FDA’s ultimate decision was a surprise. He added that he knew that the agency received additional data on eteplirsen prior to its decision, but that he had not been able to review that data in depth.

“I’m hopeful that the effectiveness of the drug ends up being validated in additional trials,” he said, referring to the agency’s approval requirement of post-market research. “It’s a terrible disease, and the current treatment options, there aren’t a lot of them. So if this drug does turn out to work in helping extend people’s lives and making them better, that would be a great thing.”

Richard Kryscio, PhD, of the Sanders-Brown Center on Aging at the University of Kentucky in Lexington also voted against recommending the accelerated approval of eteplirsen. He called the data presented at the April review as only “borderline.”

However, he pointed out that “this is a rare disease, and the more we learn about the therapy that’s being suggested here, I think the better off we’ll be.” He noted that the FDA has asked Sarepta for additional data, including dose-response data, as a stipulation of approval.

Kryscio said he encourages parents in DMD activist groups to stay involved in the postmarketing research by getting patients to enroll in postapproval studies, “so we can get the kinds of data that we need.”