Latest Drugwonks' Blog
As we move ahead in the US with more biosimilars being submitted for approval – and for interchangeability – attention must be paid to patient outcomes.
Case in point is research presented at the 2013 ACR/ARHP Annual Meeting that hasn’t as yet received the attention it deserves:
Background/Purpose: CT-P13 is an infliximab (INX) biosimilar recently approved by the European Medicine Agency. PLANETAS was a 54-week (wk) randomized double-blind parallel group multicenter Phase I study demonstrating pharmacokinetic equivalence of CT-P13 (5 mg/kg infusion every 8 wks) with INX, in patients (pts) with ankylosing spondylitis (AS) (Park W, ARD 2013;72(S3):516). Here we report results from the extension phase of the Phase I equivalence study, investigating long-term efficacy and safety of extended CT-P13 therapy and switching from INX to CT-P13 in pts with AS.
Methods:
In this open-label extension study, a total of 174/210 pts who completed PLANETAS entered into the extension phase: 88 were continuously treated with CT-P13 (maintenance group) and 86 were switched from INX to CT-P13 (switch group) for 1 additional year.
Results: At wk 54 ASAS20/ASAS40 and ASAS partial remission rates were similar between groups (CT-P13, 70.5%/58.0% and 20.5%; INX, 75.6%/53.5% and 19.8%, respectively). During the extension, ASAS20/ASAS40 rates were similar in the maintenance group (70.1%/57.5% at wk 78 and 80.7%/63.9% at wk 102) and the switch group (77.1%/51.8% at wk 78 and 76.9%/61.5% at wk 102). ASAS partial remission rates were also similar between groups; 21.8% and 21.7% at wk 78, and 27.7% and 28.2% at wk 102, respectively. An overview of the efficacy data are shown in the Table. Anti-drug antibodies (ADA) were comparable between the two groups and positivity was maintained throughout the study (maintenance group, 22.2%, 24.4% and 25.0%; switch group, 26.2%, 31.3% and 30.7%, at wk 54, 78 and 102, respectively). ADA negative pts achieved higher ASAS40 responses (maintenance group, 62.9%/61.5%/66.1%; switch group, 58.1%/60.0%/71.2% at wks 54, 78 and 102, respectively) compared with ADA-positive pts (maintenance group, 38.9%/36.8%/55.0%; switch group, 41.7%/33.3%/45.8% at wks 54, 78 and 102, respectively) with no differences between the maintenance and switch groups. The proportion of pts with ≥1 treatment-emergent adverse event (TEAE) was lower in the maintenance group (48.9%) compared with switch group (71.4%) mainly due to fewer mild and moderate AEs. Serious TEAEs were identical between groups (4 vs 4 pts). Other tolerability and safety outcomes were similar in both groups (Table). TEAEs due to hypersensitivity and infusion-related reactions were similar in both groups (5 pts in maintenance group vs 2 pts in switch group). There was 1 case of TB in each group and 1 report of prostate cancer in the maintenance group (considered unrelated to treatment).
The efficacy data was good. But the safety data is concerning:
|
Safety outcome |
CT-P13 throughout study (N=90) |
Switched from INX to CT-P13 in extension phase (N=84) |
|
|
TEAEs, n |
103 |
162 |
|
|
pts with ≥1 TEAE, n (%) |
44 (48.9) |
60 (71.4) |
|
|
Mild |
20 (22.2) |
27 (32.1) |
|
|
Moderate |
21 (23.3) |
28 (33.3) |
|
|
Severe |
3 (3.3) |
5 (6.0) |
|
|
pts with ≥1 TESAE, n (%) |
4 (4.4) |
4 (4.8) |
|
|
pts with ≥1 infection, n (%) |
23 (25.6) |
29 (34.5) |
|
|
ADA positive, n (%) |
Wk 54 |
20 (22.2) |
22 (26.2) |
|
Wk 78 |
21 (24.4) |
25 (31.3) |
|
|
Wk 102 |
21 (25.0) |
23 (30.7) |
|
|
ADA, anti-drug antibodies; ASAS, Assessment of SpondyloArthritis international Society; ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score C-reactive protein; TEAE, treatment-emergent adverse event; TESAE, treatment-emergent serious adverse event |
Biosimilarity and measurement of efficacy is only one dimension. Attention must be paid to effectiveness relative to real-world patient outcomes data. And that means a much closer pharmacovigilance examination of adverse events for both naïve and switched patients.
I recently referred to a WSJ article on advances in myeloma drugs by tweeting: Will @joewalkerWSJ @JeanneWhalen @jonathanrockoff ignore PBMs, insurers pocket rebates, make patients pay $1000s http://on.wsj.com/1Oxb69P.. Meaning will these reporters follow up with an article on myeloma treatments hat pins the blame on out of pocket drug costs on drug companies as opposed to or in combination with many other decisions undertaken by PBMs and insurers? Will they look at the impact of such medicines in reducing hospitalizations, infusions, etc that insurers pay for and are more expensive than the drugs patients must partially cover?
Below is a chart that has a link to a specific article on drug costs by each WSJ reporter and whether or not the articles discuss specific issues that would put the cost and value of drugs in context.
Maybe this will clear up the confusion.
The Biotechnology Industry Organization changed its name to the Biotechnology Innovation Organization. The group will continue using the "BIO" acronym.
This is more than just cosmetic. It demonstrates the urgency in both promoting and protecting sustainable innovation in biotechnology. If we are going to argue “value” rather than just “price,” than innovation the most important part of the conversation.
We do what we must, and call it by the best names.
Ralph Waldo Emerson
CDC sees the light …
This morning the CDC will ask the National Center for Injury Prevention and Control's Board of Scientific Counselors to appoint a new work group to review the agency's draft guideline for prescribing opioids for chronic pain. It's the next step in CDC's effort to address complaints over the secretive way in which the initial draft was developed. Public comments on the draft guideline are due Jan. 13, and the new group will be tasked with reviewing those, too.
Spotlight is a movie about how the Boston Globe's investigative team (called Spotlight) exposed the Boston Diocesan's complicity in protecting child molesters in the priesthood. The most dramatic moment in the film comes when Spotlight's chief, Walter Robinson (played by Michael Keaton) confesses that he buried a story about multiple priests abusing young boys in the in 1970s. At the time, pursuing the story -- compared to easier and less controversial investigations of police corruption, racial discrimination, government incompetency -- went against the ethos of Boston and the narrative that the Church was an integral part of Boston, where most of the reporters were raised.
While nowhere near the level of irresponsibiity, the WSJ coverage about drug costs appears to be shaped by the same set of beliefs and emotions. Every article that the WSJ has written about drug costs in 2015 (with the exception of a blog written by Ed Silverman when Pharmalot was part of the WSJ) ignored the role of pharmacy benefit managers and health insurers in hiking the cost of new drugs used by the most chronically ill patients. The have ignored the fact that PBMs, in particular, pocket 90 billion in rebates, none of which goes to reducing the cost of drugs. They have ignored the fact that the discounted drugs are less than 3 percent of total health plan spending or that as the percent increases, the cost of other services decline. They have ignored the fact that health plans have increasd the number of new targeted medicines -- drugs that work best in specific patients -- by 40 percent since 2014. (See below.)
There are more oversights as well but the list above suggests that the WSJ -- including the most recent WSJ article -- has a blind spot, not a spotlight on the issue of drug costs. The WSJ is burying the real story to sustain a narrative, at the expense of patient well-being.
Our focus in 2016 will be to create greater transparency about how drug prices are set and by who, how those decisions affect patient access to and affordability of such medicines, what affect access has on patient well-being, mortality and health costs and finally, what changes in decisionmaking can reduce spending and increase value (to patients) long term.
Further, we will look at how the reactionary defense of the randomized clinical trial is the greatest rate limiting factor in reducing the time and cost of bringing new medicines, diagnostics and devices to patients. This will NOT be an FDA pinata festival. Rather, the RCT is being protected by leading medical journals, academic research centers, major medical specialty societies and health insurers.
Pessimism is necessary in small doses, allowing us to anticipate, adapt to and often avoid failure or danger. It is also an adjuvant for change. (I don’t know what that means but it’s pithy enough to sound smart.) But apocalyptic pessimism, the pessimism that uses every event or fact to confirm certain doom unless we change our ways, is corrosive and unreliable. How do we know?
As Matt Ridley, another professional optimist observes. “For 200 years pessimists have had all the headlines, even though optimists have far more often been right.”
The steam powered train was predicted to bring ruin to England.
The industrial revolution was supposed to bring enduring misery to millions.
The poor will always be poor.
The sky is falling; the ice caps are melting.
We will run out of oil and natural gas.
Drug prices are unsustainable.
If we had followed the pessimists prescriptions (government control or manipulation of wealth, natural resources, population levels and prices) the world would be more like North Korea than North Dakota.
I will focus on the last perennial pessimistic prediction.
We heard and read a lot about drug prices being out of control, skyrocketing, unconscionable, etc.
In every era where new medicines emerge, the same claim is made. Te same bunch of pessimists trot out the same proposals: government price controls and rationing. (Now repackaged as various value frameworks.)
And each time the apocalyptic predictions that new medicines would be unaffordable or would add nothing to our lives or drive up the cost of health care were wrong.
2015 was all about drug pricing because there were so many new and expensive (relative to most consumer purchases) medicines hitting the market. But in fact the high prices – and indeed even the anger about drug prices – are a healthy sign of progress.
It means that diseases that were fatal can be cured for controlled, including Hep C, many cancers and Ebola. It means that more diagnostics are being developed to match people to the right combination of treatments and to monitor health in real time. It means that more investment in new treatments for smaller groups of people will be developed. Nothing sends a signal about the demand for better medicines than high prices.
At the same time, the high prices are forcing drug companies to do something the rest of the health care system will have to do: change business and financial models to make the case for value and increase the pressure to abandon outdated clinical development tools (randomized clinical trials) and find other ways to demonstrate the health benefits of their goods and services.
Prediction is over-rated when it is too precise. But the general trend of medical innovation, the digitization of biology, is part of a broader evolution in how we create and use the things that give us joy, insight and well-being. Our world is better because the footprint for change is getting smaller and faster. In a WSJ op-ed Andy Kessler wrote that “on Dec. 29, 1959, the physicist Richard Feynman delivered a famous speech at the California Institute of Technology titled “There is Plenty of Room at the Bottom.” He predicted almost limitless possibilities if we could “manipulate and control things on a small scale.” He nailed the next five decades of ever-shrinking realms that ultimately produced trillion-dollar markets in microelectronics, nanotechnology and bioengineering through DNA-level manipulation.…The smaller technology shrinks, the bigger the world can grow. Smaller transistors, faster processors, cheaper sensors will all allow innovators to tackle problems with tremendous precision. It’s as if, because there is plenty of room at the bottom, now there is plenty of room at the top.”
We are increasingly able to navigate and understand what Lee Hood calls “the dark matter of human biology.” New medicines are the result of our ability to explore health, wellness and disease at a molecular level.
Here’s a non-pessimistic prediction: the next trillion-dollar market will be new treatments and algorithms that control disease and keep people healthy. You have to try really hard to despair about that!
NPR/Marketplace story on price/value and PCSK9 approvals:
“The price can’t be considered a stagnant proposition. It needs to be a vibrant, living thing,” said FDA consultant Peter Pitts.
Boston Globe (Ed Silverman) on things to watch (per pharma) in 2016:
A key unknown, however, is whether drug makers will become more transparent about their pricing strategies when negotiating with these payers. This is a “very important” part of determining value for patients, noted Peter Pitts, a former Food and Drug Administration official who now heads the Center for Medicine in the Public Interest.
Happy New YearI bet you didn’t because not one media outlet covering the release of CMS drug spending data mentioned it: Instead, most of the articles started off like… oh, wait why don’t I just share with you the highest form of journalistic misdirection by the WSJ's Peter Loftus.
“Hefty price increases for a number of prescription drugs contributed to higher spending by the U.S. Medicare program in 2014, according to new government data released Monday. The Centers for Medicare and Medicaid Services identified at least five drugs that were covered under Medicare’s Part D drug benefit and had increases of 100% or more in cost per unit from 2013 to 2014. At the top of the list was Vimovo, a pain reliever whose cost-per-unit rose more than 500% after Horizon Pharma PLC purchased rights to the drug from AstraZeneca.”
Still waiting for a detailed breakdown of who did what? Don’t look under the Christmas tree because Santa isn’t delivering it this year. Neither is the WSJ or Bloomberg (who produced what can only be called a deceitful piece of reporting on the relative price of drugs in Europe and the US).
Instead after providing a description of the new CMS dashboard, Loftus concludes: “The new data emerge amid a rising debate over drug pricing. Cancer doctors have complained that the high costs of new drugs don’t seem to be tied to the benefits provided by the drugs. Presidential candidates Bernie Sanders, Hillary Clinton and Marco Rubio have criticized drug prices on the campaign trail. A U.S. Senate committee recently held a hearing about companies that have dramatically raised prices after acquiring older drugs.”
Just enough ‘information’ to reinforce the narrative that drug prices are wildly out of control because they don’t reflect value if they are new or R&D costs if they are old. Either way, the real goal of the piece is to imply that drug profits are too high, a view stoked by previous articles by Loftus and others. Any word about how PBMs and other third parties pocket $90 billion in drug rebates never shared by patients? Come on.
The late Christopher Hitchens observed that he had “become too accustomed to the pseudo-Left new style, whereby if your opponent thought he had identified your lowest possible motive, he was quite certain that he had isolated the only real one. This vulgar method, which is now the norm and the standard in much non-Left journalism as well, is designed to have the effect of making any noisy moron into a master analyst.”
Noisy morons as master analysts. Now THAT’s accurate reporting.
That makes Secretary Clinton the fourth person who is running or almost ran for president this year to call for a national assault on disease. (Ted Cruz, Mike Huckabee and Joe Biden are the others. And yes, I am sure if Donald Trump joins them it will be to announce something really, really spectacular.)
That's on the heels of a "$2 billion funding boost for NIH and a $133 million increase for FDA – levels near what the bipartisan H.R 6, the 21st Century Cures Act, sought for Fiscal Year 2016. Energy and Commerce Committee Chairman Fred Upton (R-MI) commented, “This research boost is an important milestone - we’ve made great progress, but more work remains as we seek to build upon this momentum to deliver cures now. As the Senate continues to do its work, we will continue to seek out every legislative opportunity to improve the future for patients and cures.” The momentum continues as The Hill reports, on the heels of last week’s milestone, Senate Committee on Health, Education, Labor, and Pensions Chairman Lamar Alexander (R-TN) reiterated that the Senate’s cures bill is a priority for the New Year."
And that's not all. In addition to Senators Roger Wicker and Angus King's EUREKA Act (which would authorize the Director of the National Institute of Health to work with other federal agencies to establish prize challenges to reach research milestones) there have been several other legislative proposals to encourage and reward initiatives that cure expensive and difficult to treat diseaes.
There can and will be aspects of all these proposals that can be picked apart. But as my colleague and cure strategist Jim Pinkerton points out: "history tells us that when the country commits to a goal, big things tend to happen."
Things are heating up at the CDC.
The agency’s lack of transparency regarding their development of opioid prescribing guidelines has drawn the attention of the House Committee on Oversight and Government Reform.
In a letter to CDC Director, Dr. Tom Frieden both the Chair, Representative Jason Chaffetz (R, UT) and Ranking Member, Representative Elijah Cummings (D, MD) share their displeasure at the secretive nature of the guideline development process. Per the Committee, “We have questions about why a Core Expert Group established by CDC to assist with drafting these guidelines is not considered an advisory committee under the Federal Advisory Committee Act (FACA).”
Those questions and an aggressive documents request are included in the letter which can be found here. And the Committee wants them by January 8th. Looks like there will be some people called back from their Christmas vacation at the CDC.
Perhaps the best way to address the CDC’s fairy tale process is to quote from author of Peter Pan:
“Those who bring sunshine into the lives of others cannot keep it from themselves.”
James Barrie
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
