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Saturday, January 5, 2019

Persistent Cough May Mean See Your Doctor


After suffering through a cold, many people still have a persistent cough — but why?
According to Dr. Jonathan Parsons, director of the Asthma Center at Ohio State University Wexner Medical Center, here are some reasons for a continuing cough:
  • Coughing is protective. It removes irritants from the lungs and protects the airway.
  • The cough might be due to an upper respiratory tract infection. Even after the infection is gone, you may still have some inflammation in the lungs.
  • Coughing can be worse at night. “For some patients, their cough is so severe that it disrupts their sleep to the point where they aren’t getting any sleep at all, which impacts their ability to function during the day. In that situation, you might consider taking a cough suppressant with codeine to blunt the cough reflex and assist with sleep,” Parsons said in a center news release.
A cough that lasts more than three weeks may be a chronic condition. If you’re still coughing and feeling sick after three weeks, then you should see a doctor.
Causes of a chronic cough include:
  • Uncontrolled allergies,
  • Uncontrolled asthma,
  • Side effects of medicine,
  • Acid reflux.
Persistent cough might be a symptom of a serious illness.
“If you’re coughing up blood, spiking fevers or have significant shortness of breath associated with the cough, you need to be evaluated quickly. You could have walking pneumonia. If you’re a smoker, it could be cancer. A doctor will examine you to determine the cause of the cough and establish a treatment plan,” Parsons said.
More information
Harvard University Medical School offers more on the causes and cures for a persistent cough.
SOURCE: Ohio State University Wexner Medical Center, news release, Dec. 28, 2018

Vericel Publishes Data From 954 Burn Patients Treated With Epicel


Vericel Corporation (Nasdaq:VCEL), a leader in advanced cell therapies for the sports medicine and severe burn care markets, today announced the publication of outcomes data for 954 burn patients treated with Epicel (cultured epidermal autografts) in the Journal of Burn Care and Research. The results demonstrated an increased survival rate for patients treated with Epicel when compared to results reported for patients in the National Burn Repository with comparable burns.
Epicel is a permanent skin replacement produced from patients own cells and indicated for use in adult and pediatric patients who have deep dermal or full thickness burns comprising a total body surface area (TBSA) greater than or equal to 30%. The probable benefit of Epicel, mainly related to survival, has been previously demonstrated in two Epicel databases and one physician-sponsored study.
The publication summarized outcomes for the largest cohort of patients treated with Epicel published to date. The data set was compared to the National Burn Repository annual report which is the largest resource on epidemiology of thermal injury for patients admitted to burn centers and contains outcome data for 177,498 burn patients.
The overall mortality rate by burn size was lower for Epicel-treated patients than that reported in the National Burn Repository 2016 Report. The mean TBSA of burns in patients from the Epicel cohort was 67.5%, with an overall survival at discharge rate of 84.4% (804/953). According to the data set reported in the 2016 American Burn Association National Burn Repository, burns greater than 65 to 70% TBSA are associated with a 50% case mortality rate.1This comparative advantage in survival outcome was found to be consistent in both pediatric and adult patients treated with Epicel.
This new dataset demonstrating increased survival rates for patients treated with Epicel over a period of 25 years supports the strong clinical benefit achieved with Epicel in large full thickness burns, said Jon Hopper, Vericels chief medical officer. These data are important to patients and physicians since Epicel is the only FDA-approved permanent skin replacement for adult and pediatric patients with full-thickness burns.
The publication is entitled Twenty-five Years Experience and Beyond with Cultured Epidermal Autografts (CEA) for Coverage of Large Burn Wounds in Adult and Pediatric Patients, 1989-2015 and the full abstract is available on pubmed:

13 early signs of Parkinson’s


The hallmark symptoms of Parkinson’s disease are tremors and slow, rigid movements. Small changes in a person’s movements and behavior can signal the onset of Parkinson’s disease before diagnosis.
Parkinson’s disease is a nervous system disorder that affects around 1 percent of people aged 65 years and older. Symptoms usually develop slowly over several years. They may be subtle at first, so early signs are easy to miss.
If someone notices symptoms of Parkinson’s disease, they should consider contacting their doctor for more information. Early treatment can improve the condition’s long-term outcome.
In this article, we cover 13 early signs of Parkinson’s disease.

1. Tremors

Many healthcare professionals consider tremors to be a key characteristic sign of Parkinson’s disease. Tremors involve a persistent twitching or shaking of the hands, legs, or chin.
Tremors associated with Parkinson’s disease are called “rest tremors.” This means that the tremors stop when a person uses the affected body part.
Tremors are very subtle when they first appear. At this stage, the person experiencing the tremors is usually the only one who notices them. Tremors will gradually worsen as the disease progresses.
Tremors typically appear on one side of the body and then spread to other parts of the body later on.

2. Difficulty walking

Subtle changes in a person’s walking pattern could be an early sign of Parkinson’s disease.
Someone who has Parkinson’s disease might walk slowly or drag their feet as they walk. Many refer to this as a “shuffling gait.”
The person might walk at an irregular pace, suddenly walking faster or slower or changing the length of their stride.

3. Cramped or small handwriting

Micrographia is a disorder that involves abnormally small or cramped handwriting.
Doctors associate micrographia with medical conditions that affect the nervous system, or neurodegenerative disorders, such as Parkinson’s disease.

4. Loss of smell

Hyposmia occurs when someone loses their ability to smell. This is also called olfactory dysfunction. A loss of smell is a relatively common symptom, affecting 70–90 percent of people with Parkinson’s disease.
Loss of smell is one of the most noticeable symptoms of Parkinson’s disease that is not related to movement. It can appear several years before the disease affects a person’s movement.
People who have hyposmia as a symptom of Parkinson’s disease might experience:
  • a dulled sense of smell
  • difficulty detecting odors
  • difficulty identifying odors
  • difficulty telling the difference between odors
Doctors use smell identification tests to diagnose hyposmia, but the accuracy of these tests varies widely.
Having hyposmia does not always mean that someone has Parkinson’s disease. A person’s sense of smell can change for many reasons, such as age, smoking, or exposure to harsh chemicals. Hyposmia is also a symptom of other medical conditions, including Alzheimer’s disease and Huntington’s disease.

5. Sleep problems

Parkinson’s disease can severely affect a person’s ability to sleep. People who have Parkinson’s disease may experience a wide range of sleep-related symptoms, including:

6. Poor balance

Parkinson’s disease specifically targets nerve cells called basal ganglia, which reside deep within the brain. Basal ganglia nerves control balance and flexibility, so any damage to these nerves can impair a person’s balance.
Doctors use a test called the pull test to assess a person’s balance. The pull test involves a healthcare professional gently pulling a person’s shoulders backward until they lose their balance and recording how long it takes them to regain it.
Healthy individuals recover after one or two steps, while people with Parkinson’s disease may take a higher number of smaller steps to fully balance themselves.

7. Bradykinesia

Bradykinesia is a term that means slowness or absence of movement.
Bradykinesia causes a variety of symptoms, such as stiffness of the limbs and slow movements. A person who has bradykinesia might walk slower or have difficult starting a movement.
Some people who have this symptom might misinterpret it as muscle weakness. However, this symptom does not affect muscle strength.

8. Facial masking

Facial expressions involve many subtle, complex muscle movements. People with Parkinson’s disease often have a reduced ability to make facial expressions. This is called facial masking.
Facial masking is related to bradykinesia. The facial muscles move more slowly or rigidly than usual. People who have facial masking may appear blank or emotionless, though their ability to feel emotions is not impaired. Facial masking can also cause someone to blink their eyes slower.
A person with facial masking might have difficulty communicating with others because changes in their facial expressions are less noticeable than usual.

9. Vocal changes

Changes in the volume and quality of a person’s voice is another early sign of Parkinson’s disease.
Vocal changes may involve speaking in a softer tone, or starting to speak at a usual volume and then the voice becomes softer or fades away.
In other cases, a person might lose the usual variation in the volume and tone of their voice, so that the voice appears monotonous.

10. Stooping or hunched posture

People who have Parkinson’s disease may notice changes in their posture due to other symptoms of the disease, such as muscle rigidity.
People naturally stand so that their weight is evenly distributed over their feet. However, people who have Parkinson’s disease may start bending forward, making them appear hunched or stooped over.

11. Constipation

Constipation is a common problem that can have a wide range of causes. Constipation is one of the most common non-motor symptoms associated with Parkinson’s disease. Nearly 25 percent of people with the condition experience constipation before they develop motor symptoms.

12. Psychological symptoms

Parkinson’s disease can severely affect a person’s psychological well-being. The disease lowers the body’s natural levels of dopamine, which can cause changes in mood and behavior.
Some psychological symptoms associated with Parkinson’s disease include:

13. Weight loss

People with Parkinson’s disease might experience mild to moderate weight loss for several reasons.
Tremors and other motor symptoms associated with Parkinson’s may increase the body’s natural energy requirements. Non-motor symptoms, such as loss of smell, depression, or digestive issues, might cause people to eat less, which may result in weight loss.

Summary

Parkinson’s disease is difficult to diagnose, especially in the earlier stages. This is because the symptoms are subtler and more sporadic. However, knowing what symptoms to look for may encourage people to seek medical attention before they progress.
Early symptoms of Parkinson’s disease include:
  • tremors
  • difficulty walking
  • cramped or small handwriting
  • loss of smell
  • sleep problems
  • poor balance
  • bradykinesia
  • facial masking
  • voice changes
  • stooping or hunched posture
  • constipation
  • psychological symptoms
  • weight loss
Having these symptoms does not always mean that a person has Parkinson’s disease. People over the age of 60 should consider speaking with their healthcare provider if they experience any of the symptoms listed above.
Early diagnosis leads to earlier treatment, which can improve a person’s overall quality of life.

Coverage denied Medicaid patients as layers of private companies profit


Marcela Villa isn’t a big name in health care — but she played a crucial role in the lives of thousands of Medicaid patients in California. Her official title: denial nurse.
Each week, dozens of requests for treatment landed on her desk after preliminary rejections. Her job, with the assistance of a part-time medical director, was to conclusively determine whether the care — from doctor visits to cancer treatment — should be covered under the nation’s health insurance program for low-income Americans.
She was drowning in requests, she said, and felt pressed to uphold most of the denials she saw. “If it was a high-dollar case, they tried to deny it,” Villa said. “I told them you can’t deny it just because it’s going to cost $20,000.”
Villa, 32, did not work for the government. She did not even work for an insurer under contract with the government. She worked for a company now called Agilon Health. Owned by a private equity firm, it’s among the legion of private subcontractors looking to profit from Medicaid patients.
California’s Medicaid program, known as Medi-Cal, has determined that the Long Beach company, which was paid to coordinate care for about 400,000 patients, improperly denied or delayed care for at least 1,400 of them, state officials confirmed. The state Department of Managed Health Care is investigating further.
The state findings, along with internal company documents and a whistleblower complaint obtained by Kaiser Health News, shine a light on the potential dangers of outsourcing care for poor people. Government oversight, not rigorous to begin with, fades as taxpayer money filters down through layers of companies eager to seize on Medicaid’s substantial growth under the Affordable Care Act. Medicaid officials say they have authority only over the health plans, not their subcontractors.
In an interview, Agilon chief executive Ron Kuerbitz acknowledged that some patients experienced modest delays in care but disputed that any suffered unjustified denials. He noted that an internal investigation by the company found no evidence of “systemic” denials and that most of the problems existed before Agilon took over another firm, Primary Provider Management Co., in 2016.
“We did the right thing when it was identified,” Kuerbitz said of the problems. “We disclosed it, we investigated it, and we pursued a remedial path.”
Such concerns are not isolated to one company. Last year, KHN reported on similar irregularities at SynerMed, a Medicaid subcontractor that coordinated care for about 650,000 patients in California.
In response to a whistleblower complaint, the state Medicaid program said it found “widespread deficiencies” at SynerMed that put patients “in imminent danger of not receiving medically necessary healthcare services.” The company’s staffers had falsified documents for years to cover up improper denials of care, according to state officials.
Then SynerMed abruptly shut down, and some of its patients moved to Agilon’s medical groups.

SKIMPING ON SERVICES?

Nearly three-quarters of the 73 million low-income Americans on Medicaid are now in managed care, in which states pay health insurers fixed monthly amounts for each enrollee to cover the range of services they need.
Under this system, keeping patients as healthy as possible is one way to make money. Another is to deny or skimp on services.
Increasingly, Medicaid plans outsource the work of managing patients’ health and medical treatment to subcontractors like Agilon — passing along a share of the government money coupled with the financial risk posed by a fixed budget.
These firms can be powerful gatekeepers. They run physician groups, bear responsibility for forming doctor networks and judge whether a request for care is necessary.
Agilon is a big player in California — doing business with insurers such as Molina Healthcare and Blue Shield of California — and it’s now expanding in other states like Texas and Ohio.
Primary Provider Management Co. ran several medical groups, including Vantage Medical Group with more than 5,000 physicians across Southern California. By building off PPMC’s base of Medicaid enrollees in California, the New York private equity firm that owns a majority stake in Agilon — Clayton, Dubilier & Rice — sought to coordinate care in Medicaid and Medicare Advantage plans across the country. (CD&R did not respond to interview requests.)
For several years, the problems at PPMC, and then Agilon, went undetected. Then, in early 2018, Agilon disclosed to the California Department of Managed Health Care its discovery that employees had been altering records prepared for auditors, which it said was not known to top management.
According to an internal report, completed in May and obtained by KHN, staffers had been falsifying documents since at least 2014 to pass audits by health plans. Employees were changing dates, for example, to cover up delays or withholding certain files so they couldn’t be reviewed.
That same month, an anonymous whistleblower sent a letter to health plans and government officials, urging them to investigate “illegal, unethical” conduct at the firm. “Senior management delays treatments for cancer patients without any regard of patient’s well-being, to save their dollars,” the whistleblower wrote in a two-page letter reviewed by KHN. “They brag about how profitable we are.”
In response to the allegations raised by the whistleblower and state, Agilon opened another internal investigation. That second report, finished in June, found inadequate staffing to handle the volume of work, various shortcuts and practices outside industry “norms” and improperly denied claims. Both internal reports were released to the state.
A top official Inland Empire Health Plan, one of the largest Medicaid insurers in the country, said the plan also looked into Agilon’s conduct and found instances in which its patients were harmed.
In an interview, Inland Empire CEO Bradley Gilbert said Agilon denied a patient’s transfusions for anemia, causing the person to be hospitalized. It also improperly denied cardiac rehabilitation to a patient recovering from a heart attack, he said. Inland Empire canceled its contract with Agilon’s Vantage Medical Group in August, he said.

A ‘MANAGER TOLD ME TO DO IT’

Agilon’s June report depicts an operation that was often stretched thin: Nurses were handling 120 to 200 requests for care per day, on average, with no full-time medical director to review the findings.
From 2014 until May, the company relied on a family physician who was working 10 to 12 hours a day running his own medical practice, according to the report.
Dr. Reuel Gaskins was busy seeing his own patients at the Hampton Medical Clinic in Riverside, Calif., where a red neon sign flashes “Open” in the front window. In an interview, Gaskins said he reviewed cases during breaks throughout the day and after normal work hours. He said he left Agilon in April.
Ultimately, Agilon’s internal investigation found that patient care may have been denied 439 times since 2014 without a physician’s review of the medical records — a potential violation of state law. Under California law, only a licensed physician or health care professional who is “competent to evaluate the specific clinical issues involved” can determine medical necessity.
Gaskins said he was not aware of allegations that medical decisions were made without his review until he was interviewed by Agilon’s lawyers.
“That’s inappropriate and unacceptable,” he said. “It really bothered me when I heard about it.”
The June report also found that Villa helped alter 20 files at the request of a supervisor in 2014 so her employer could pass an upcoming audit by an insurer.
A “manager told me to do it,” Villa said in an interview. “They were so adamant that everything look perfect for the auditors.”
A few days after the company’s lawyers made that discovery, Agilon sent Villa home on paid leave, the nurse said. She said that when she returned to work in August, she found she had been replaced as denial nurse, and shortly after that, she was fired.
Meanwhile, in recent months, Agilon has mended its relationships with some insurers and won new Medicaid contracts.
Consumer advocates worry that the concerns surrounding Agilon and SynerMed signal a much larger problem in the burgeoning Medicaid managed-care industry.
“These private entities get very little oversight,” said Linda Nguy, a policy advocate at the Western Center on Law & Poverty in Sacramento, “and there’s real harm being done to patients.”

Hospitals post prices online; patients remain befuddled


As of Jan. 1, in the name of transparency, the Trump administration required that all hospitals post their list prices online. But what is popping up on medical center websites is a dog’s breakfast of medical codes, abbreviations and dollar signs — in little discernible order — that may initially serve to confuse more than illuminate.
Anyone who has ever tried to find out in advance how much a hospital test, procedure or stay will cost knows the frustration: “Nope, can’t tell you” or “It depends” are common replies from insurers and medical centers.

While more information is always welcome, the new data will fall short of providing most consumers with usable insight.
That’s because the price lists displayed this week, called chargemasters, are massive compendiums of the prices set by each hospital for every service or drug a patient might encounter. To figure out what, for example, a trip to the emergency room might cost, a patient would have to locate and piece together the price for each component of their visit — the particular blood tests, the particular medicines dispensed, the facility fee and the physician’s charge, and more.
“I don’t think it’s very helpful,” said Gerard Anderson, director of the Johns Hopkins Center for Hospital Finance and Management. “There are about 30,000 different items on a chargemaster file. As a patient, you don’t know which ones you will use.”
And there’s this: Other than the uninsured and people who are out-of-network, few actually pay full charges.
The requirement to post charges online in a machine-readable format, such as a Microsoft Excel file, came in a 2018 guidance from the Trump administration that builds on rules in the Affordable Care Act. Hospitals have some leeway in deciding how to present the information — and currently there is no penalty for failing to post.
“This is a small step” toward price transparency amid other ongoing efforts, Centers for Medicare & Medicaid Services Administrator Seema Verma said in a speech in July.
But finding the chargemaster information on a hospital’s website takes diligence. Patients can try typing the hospital’s name into a search engine, along with the keywords “billing” or “chargemaster.” That might produce a link.
Even when consumers do locate the lists, they might be stymied by seemingly incomprehensible abbreviations.
The University of California San Francisco Medical Center’s chargemaster, for example, includes a $378 charge for “Arthrocentesis Aspir&/Inj Small Jt/Bursa w/o Us,” which is basically draining fluid from the knee.
At Sentara in Hampton Roads, Va., there’s a $307 charge for something described as a LAY CLOS HND/FT=<2.5CM. What? Turns out that is the charge for a small suture in surgery.
Which services, treatments, drugs or procedures a patient will face in a hospital stay is often unknowable. And the charge listed is just one component of a total bill. Put simply, an MRI scan of the abdomen has related costs, such as the charge for the radiologist who reads the exam.
Even something as seemingly straightforward as an uncomplicated childbirth can’t easily be calculated by looking at the list.
Comparisons between hospitals for the same care can also be difficult.
An uncomplicated vaginal delivery charge at the Cleveland Clinic’s main campus is $3,466.
Looking for that same information on the Minnesota Mayo Clinic‘s online chargemaster page shows two listings, one for $3,030, described as “labor and delivery level 1 short” and the other for $5,236, described as “labor and delivery level 2 long.” But, what’s a short labor? What’s a long one? How is a patient who didn’t go to med school supposed to know the difference?
Also, those are just the charges for the actual delivery. There are also per-day room charges for mom and the newborn, not to mention additional charges for medications, physicians and other treatments.
To get at the total estimated charge, California requires hospitals to report charges for a select number of such “bundles” of care, called “diagnosis-related groups,” or DRGs, in Medicare jargon.
At the University of California-San Francisco’s hospital, for example, there are two chargemaster line items for vaginal childbirth: One is $5,497 and the other is $12,632. But there’s no indication how these differ. Consumers might then turn to the “bundled” cost based on those DRGs, where the ancillary costs are included. That lists the total charge for an uncomplicated childbirth at an astounding $53,184.
A UCSF spokeswoman said no officials were available to comment on this figure.
Though chargemaster rates are quite different from the lower, negotiated rates that insurers pay, they do become the basis for what patients pay who are without insurance or who are treated at hospitals outside their insurer’s network. Out-of-network patients are often surprised when they get what are called “balance bills” for the difference between what their insurer pays toward their care and those full charges.
Still, even knowing chargemaster rates “would be entirely unhelpful” in fighting a high balance bill, said Barak Richman, a law professor at Duke University who has written extensively about balance bills and hospital charges.
“Chargemasters are enormous spreadsheets with incredibly complicated codes that no one short of a billing expert would be able to make sense of,” he said.
Nevertheless, some experts say that merely making the charges public shines a light on the often very high — and widely varying — prices set by facilities.
Even if those charges are only “what hospitals would like to receive,” posting them publicly could make hospitals “totally embarrassed by the prices,” said Anderson at Hopkins.
Billing expert George Nation, a finance professor at Lehigh University, said that rather than posting chargemaster lists, hospitals should be required to provide the average prices they accept from insurers. Hospitals generally would oppose that, saying negotiated rates are a trade secret.
It’s unclear that the lists will have much impact. “It’s been the norm here in California for over a decade,” said Jan Emerson-Shea, vice president of external affairs for the California Hospital Association. Even so, “from a practical standpoint, I’m not sure how useful this information is,” she said. “What an individual pays to [the] hospital is going to be based on what their insurer covers.”
That could include such things as the annual deductible, whether the facility or physicians involved in the care are in-network and other details.
“The hospital piece is just a small piece,” said Ariel Levin, senior associate director for state issues at the American Hospital Association.
Still, “the biggest concern is it falls short of that end goal because it really doesn’t help consumers understand what they are going to be liable for,” she said.

2 years after sluggish 2016, new drug approvals hit their stride in 2018


If in 2017, the FDA was trying to make up for lost time, the agency went into overdrive in 2018, approving more than 50 new molecular entities. The strong showing in 2018 followed a more-than-respectable 46 NMEs the previous year, which came after an anemic 2016 that saw only 22 approvals.
By the FDA’s count, it approved 59 NMEs in 2018, topping its previous record of 53 in 1996. If you’re wondering why our count is different, there are multiple reasons. We included two biologics—Andexxa and Jivi—and Inbrija, a new formulation of levodopa, in our list. We omitted other drugs, such as Akynzeo. The combination of netupitant and palonosetron first earned the FDA’s OK as an oral drug for the prevention of nausea in patients undergoing chemotherapy in 2014. The FDA approved an injectable version of Akynzeo that uses a prodrug of netupitant for the same indication in 2018 and listed it as an NME. We also omitted Omegaven, the active ingredient of which is fish oil triglycerides, and Annovera, a contraceptive ring that releases hormone medications that are already available on the market. And though the FDA listed cancer drugs Braftovi and Mektovi separately, we considered them a combination treatment, like Zepatier (elbasvir/grazoprevir) in 2016.
With that out of the way, let’s get down to what happened in 2018.
Predictably, cancer drugs came out tops with 16 approvals,with blood cancer treatments coming out slightly ahead of those for solid tumors. AstraZeneca’s Lumoxiti and Verastem’s Copiktra were both approved as third-line treatments for blood cancers—the former for hairy cell leukemia, a rare, slow-growing cancer, and the latter for chronic lymphocytic leukemia, follicular lymphoma and small lymphocytic lymphoma.
Several drugs were indicated for genetically defined cancers: Array BioPharma’s Mektovi/Braftovi for BRAF-mutated melanoma and Agios’ Tibsovo for relapsed or refractory acute myeloid leukemia with an IDH1 mutation, as well as a trio of drugs from Pfizer, namely Vizimpro for EGFR-mutated non-small cell lung cancer, Lorbrena for ALK-positive NSCLC, and Talzenna for BRCA-mutated, HER2-negative breast cancer. And who could forget Bayer and Loxo’s Vitrakvi, the “tissue-agnostic” drug that won approval to treat patients whose tumors feature a neurotrophic receptor tyrosine kinase gene fusion?
The number of rare disease approvals almost matched that of cancer approvals. Thrombocytopenia saw two new approvals in Doptelet and Tavalisse, as did hereditary transthyretin amyloidosis (hATTR) in Alnylam’s Onpattro and Akcea/Ionis’ Tegsedi. Onpattro also had the distinction of being the first approved drug for polyneuropathy stemming from hATTR, as well as the first small interfering RNA, or siRNA, medicine.
GW Pharma’s Epidiolex became the first cannabis-based medicine to get past the FDA. Approved for two rare forms of epilepsy, Dravet and Lennox-Gastaut syndromes, Epidiolex’s active ingredient is cannabidiol, a Schedule I drug with “no currently accepted medical use,” which had to be rescheduled by the Drug Enforcement Administration (DEA) before GW could roll it out. While the DEA only rescheduled cannabidiol in the form of Epidiolex, GW Pharma’s historic approval could pave the way for other companies working on cannabis-based treatments.
Hepatitis C, the indication that seemed to keep on giving, at least these past few years, was absent from 2018’s crop, while HIV and migraine logged three new drugs apiece. Gilead’s HIV combo drug, Biktarvy, is expected to garner as much as $10 billion in sales, arriving in time to help stave off pressure on the Big Pharma’s hepatitis C franchise. And TaiMed’s Trogarzo, approved for multidrug-resistant HIV-1, is the first HIV therapy with a new mechanism of action approved in more than a decade.
Migraine was also a hot area, with several players racing to get a first-in-class nod for their CGRP inhibitors. Amgen and Novartis won that distinction with Aimovig, which was approved in May. Teva’s Ajovy and Eli Lilly’s Emgality followed suit in September, but there are still more to come. Allergan and Biohaven are both working on oral CGRP drugs, which represent a more attractive option for patients.
As individual drugmakers go, there was one clear winner: Pfizer, which didn’t get a drug approved until September but ended up with four approvals—all in oncology—over the course of two months. Its second approval of 2018, PARP inhibitor Talzenna, earned the FDA’s OK for BRCA-mutated, HER2-negative breast cancer, but the Big Pharma is looking to expand its repertoire to other cancers, including ovarian, pancreatic and lung.
Most of the other companies on this year’s list got just one approval apiece, with the exception of Shire and AstraZeneca, which both got two. Bayer, Eli Lilly, Novartis, and Shionogi also got two, but their second approvals were all for partnered drugs. For the second year in a row, Bristol-Myers Squibb was the only top 15 pharma company that went without.
So what was behind the boost in drug approvals in 2018? Evercore ISI analyst Jon Miller says it’s hard to say that there’s a trend across the board: “The most I would say is these things go in waves. That said, the agency over the past couple of years has been increasingly conciliatory. And I don’t mean that they necessarily are letting bad drugs through, but they have been maybe putting up less resistance to certain things.”
He pointed to the controversial approval of Exondys 51 in 2016 as the bellwether for this: “The FDA is becoming more willing, especially in rare diseases and restricted patient populations with high unmet need, to approve drugs on what might have counted as thin evidence five or 10 years ago.”
And while some people thought Exondys had been approved on “relatively shaky evidence,” Miller said that it didn’t necessarily mean that the FDA was going to approve everything that came its way. He doesn’t think the evolution in the agency’s thinking is limited to the past two years: “I think this is a trend that has been developing for a little while and there are natural ebbs and flows in the approval cycle, as pipelines ebb and flow naturally.”
A more telling statistic would be approval rate, he said, or the number of new drug applications that are approved each year as a percentage of total applications filed. But this can be hard to track, as the FDA does not publicly release applications that are submitted but not approved, and the only real source for rejected applications is when a company announces that it has received a complete response letter, a request for more data, or the like. The FDA did not respond to a request for comment by press time.
“According to the regulator’s own statistics applications have also risen, but not at the same rate; although not much data have been seen for 2018 yet. This uptick presumably largely reflects the FDA’s internal efforts to get new drugs to market more quickly and efficiently. Many believe that the jump in numbers is also a result of lower efficacy hurdles,” wrote EP Vantage in its 2019 Preview.
One question is what this “clement regulatory climate,” to quote Vantage, might mean for the future.
“A lot of this bull market has been driven by a super-permissive FDA. This has emboldened risk-taking by both biotech companies and investors,” one investor, who asked not to be named, told Vantage.
“[If] this surge in accelerated applications is a symptom of an industry that has been encouraged to push forward too quickly—in some cases to the detriment of both patients in terms of effectiveness and safety and investors in terms of weak commercial prospects—an era of regulatory permissiveness could hurt the sector over the longer term,” Vantage wrote.
Without further ado, here’s our list of drugs that earned FDA approval in 2017.