Mary Caffrey

home

authors

mary-caffrey

Hospital mergers, drug prices, and non-compete clauses for the rank and file are all targets of President Joe Biden’s pen today as he signed a sweeping executive order instructing federal departments and agencies to reshape what he called “booming” economy by putting workers first, encouraging higher wages and the opportunity for mobility.

The order spans sectors from banking to transportation with 72 specific initiatives, including several that target healthcare, which is already undergoing upheaval amid the COVID-19 pandemic, which has exacerbated shortages of doctors and nurses, strained supply chains, and pushed veteran administrators into retirement.

“For decades, corporate consolidation has been accelerating,” a statement issued with the order reads. “In over 75% of U.S. industries, a smaller number of large companies now control more of the business than they did twenty years ago. This is true across healthcare, financial services, agriculture and more. That lack of competition drives up prices for consumers.”

The statement cited data claiming that mark-ups have tripled, raising costs for necessities like prescription drugs, hearing aids, and internet service—which became essential during the pandemic as telehealth became the only way to see a doctor.

Key items in Biden’s executive order include:

Making it easier to change jobs, including between states, by reducing occupational licensing requirements and limiting non-compete agreements.

Reducing prescription drug prices by allowing programs run by states and tribes that import drugs from Canada.

Promoting more procurement opportunities for small business with federal agencies.

Empowering antitrust agencies, including the Federal Trade Commission, to address problems surrounding consolidation in certain industries, including healthcare, where mergers have left some rural areas with no hospital.

The order creates a White House Competition Council the track progress on the initiatives and agencies’ response.

Consolidation in healthcare over the past decade—mergers of hospitals into larger systems, acquisition of practices, and vertical integration of health plans and pharmacy benefit managers (PBMs)—has drawn fire from consumer and antitrust advocates who say the trend works against keeping down costs, especially when one looks at some individual markets.

The order directs the Justice Department and the FTC to examine guidelines on hospital mergers to ensure that patients are not harmed.

Recent trends also work against reining in the price of prescription drugs, because powerful PBMs can dictate which drugs appear on formularies, demand rebates, or impose fees. Just this week, a study by authors at USC’s Schaeffer Center found that Medicare overspent by $2.6 billion in 2018 on commonly prescribed generic drugs compared with prices charged by Costco.

Biden’s order directs HHS to do the following:

Support hospital price transparency rules and to finish implementing bipartisan federal legislation to address surprise hospital billing. This is significant, because many wondered the fact of the transparency rules imposed at the very end of the Trump administration.

Restore a rule from the Obama era that insurers selling plans under the federal marketplace, created by the Affordable Care Act, must have at least one standard design to serve as a benchmark for consumers to compare with other companies. This concept was scrapped under the Trump administration.

Directs the FDA, which is part of HHS, to work with states and tribes on safe import practices under the Medicare Modernization Act of 2003.

Increases support for generic and biosimilar drugs and allows 45 days for a comprehensive plan to combat high prescription prices.

Empowers FTC to ban “pay for delay” and similar practices that keep low cost drug or biosimilar options off the market.

Articles

Hospital mergers, drug prices, and non-compete clauses for the rank and file are all targets of President Joe Biden’s pen today as he signed a sweeping executive order instructing federal departments and agencies to reshape what he called “booming” economy by putting workers first, encouraging higher wages and the opportunity for mobility. 

Biden Executive Order Takes Aim at Drug Prices, Hospital Mergers

Immunotherapy is transforming treatment of urothelial cancer, but there’s much work to be done in biomarker development to fill knowledge gaps and build better precision medicine approaches, according to 

, M.D., director of bladder cancer research at 

Weill Cornell Medicine’s Englander Institute for Precision Medicine

Faltas commented on three abstracts presented earlier this month during the 2021 Annual Meeting of the American Society of Clinical Oncology. Two were about trials that examined immunotherapy combinations in the neoadjuvant setting. The third concerned the use of Bavencio (avelumab) as maintenance therapy.

“So, what is the biological rationale for early systemic immunotherapy?” Faltas asked as his presentation began. He explained how surgery for primary and metastatic tumors in urothelial cancer is often not enough, because examinations of “micrometastatic clones” from within the same patient have shown how cancer has already spread by the time surgery occurs.

As Faltas explained, neoadjuvant cisplatin-based chemotherapy can improve overall survival, but some patients could benefit from additional therapy. Others are not eligible for cisplatin-based treatment.

Tecentriq (atezolizumab) with chemotherapy

 conducted by Samuel Funt, M.D., and colleagues from Memorial Sloan Kettering in which patients with muscle-invasive bladder cancer received a multiple-step regimen: (1) a single dose of the immunotherapy Tecentriq (atezolizumab), (2) a combination of gemcitabine, cisplatin, and Tecentriq for four cycles, every three weeks, (3) a final dose of Tecentriq, and(4) surgery.

The study met its primary end point, with, 27 of 39 patients (69%) achieving <pT2N0 at the time of radical cystectomy, including 44% who achieved pT0N0, which is considered a complete response rate.

Combining two immunotherapy agents could be an option for patients not eligible for cisplatin therapy, but results from a phase 1b trial were disappointing. Patients who took neoadjuvant Opdivo (13 patients) or a combination of Opdivo and lirilumab (30 patients) tolerated the therapy well, by the complete response rates were low especially for Opdivo alone.

As Faltas explained more phase 3 trials involving neoadjuvant therapy are planned, for both cisplatin eligible and ineligible patients. For cisplatin-ineligible patients, combinations include trials with bempegaldesleukin — "bempeg" for short — and Opdivo or Keytruda  (pembrolizumab) plus Padcev (enfortumab vedotin-ejfv). For cisplatin-eligible patients, combinations include an oral IDO inhibitor linrodostat with standard chemotherapy, with or without Opdivo. Other combinations involve Imfinzi (durvalumab) or Keytruda with the gemcitabine/cisplatin chemotherapy regimen.

Faltas outlined the biomarkers being studied to predict responses: tumor mutational burden, immune gene signatures, CDA density, TGF-beta signatures, among others. 

However, overall, identifying a reliable clinical biomarker of response to immunotherapy has been elusive,” he said.

There are still many unanswered questions, said Faltas: “Are different immunotherapy combinations more effective than single agents in randomized controlled trials? Can we select patients who are likely to benefit form neoadjuvant immunotherapy based on a biomarker? And, finally, what is the best sequence of neoadjuvant, and maintenance lines of therapy?

Faltas then moved to a post-hoc subgroup analysis of JAVELIN 100, a maintenance therapy study that has already resulted in an 

 for patients whose locally advanced or metastatic urothelial cancer has not progressed after platinum-based chemotherapy

The subgroup analysis involving the 700 patients who were randomized to Bavencio with best supportive care or best supportive care alone. An overall survival benefit was seen with Bavencio-based treatment across subgroups: upper- or lower-tract tumors, both metastatic or locally advanced, and unresectable disease prior to chemotherapy.

Those in the Bavencio group had prolonged survival compared with those in supportive care-only arm, especially among patients with upper tract tumors for whom survival improved from 17.4 months to 19.9 months. In patients with lower-tract disease, survival improved from 14.1 months to 22.5 months; and in the metastatic disease arm, survival increased 14.1 months vs. 18.2 months.

"We can see that the clinical benefit of maintenance avelumab is consistent across the majority of these subgroups," Faltas said. 

"My interpretation of this data is that maintenance avelumab should be offered to all patients who would qualify," he continued. 

Patients with the luminal molecular subtype may not derive as much benefit, although, the confidence intervals are wide, making the finding hard to interpret, he noted/

Faltas then reviewed data from several studies showing the challenges that remain in developing biomarkers in UC, in part because biomarkers can evolve in a given cancer over time.

“I suggest that the relationship between molecular subtypes in response to immunotherapy should be viewed as a continuum,” he said.

Neuroendocrine tumors are rare but are “exceptionally responsive to immunotherapy,” and basal tumors also likely see a high degree of benefit from immunotherapy, observed Faltas. Other subtypes may be less responsive or even resistant to immunotherapy. 

“In order to leverage this understanding to develop a clinical biomarker, we need a single sample classifier,” he said, showing an example of one such tool. But even the way molecular subtypes are named doesn’t speak to the way different cell components function when it comes to the way they behave in cancer.

A presentation at the 2021 American Society of Clinical Oncology meeting earlier this month reviewed recent findings from trials investigating the treatment of urothelial cancer.

In Urothelial Cancer, Most Subtypes Benefit From Maintenance Bavencio (Avelumab), Faltas Says

When younger women show up at the emergency room with chest pain, they wait longer to be seen, have fewer tests, and are less likely to be admitted than men, according to new research.

The study, which will be presented next week during the 70th American College of Cardiology Scientific Session, is the first to examine how chest pain is managed among adults who are too young for Medicare. This study looked at adults age 18-55 years. Heart disease is the leading cause of death for women, and it’s showing up more frequently 

, with a 2019 study citing rising obesity and diabetes rates as culprits. Roughly one-third of women hospitalized for a heart attack are younger than 55.

Darcy Banco, M.D.,the study’s lead author and a resident at NYU Langone Health, said women should seek care at the first sign of trouble, which can include chest pain, nausea, vomiting, fatigue, sweating, back pain, or trouble breathing. 

Besides getting less attention once they arrive at the ER, Banco said earlier research shows women wait longer than men to seek care when they have heart attack symptoms.

“The most important thing a woman can do is to seek medical care if she is worried and to ask specific questions of her doctor,” she said.

The new findings are derived from data collected from 2014-2018 by the CDC, through the National Hospital Ambulatory Medical Care Survey. From this survey data, researchers estimated that 29 million visits to the ER for chest pain involve adults aged 18-55, and women accounted for 57% of these visits.

Women were just as likely as men to come to the hospital by ambulance, but once there, took longer to be triaged and tested. Banco’s study found women waited longer to be seen by a clinician, and were less likely to receive an electrocardiogram, or EKG, the test used to diagnose a heart attack.

Women were triaged as urgent or emergent 57.1% of the time, compared with 63.0% of the time in men.

Women waited 45 minutes on average to see a doctor, compared with 37 minutes for men, and a cardiology consult happened with 12.3% of men compared with 8.5% of women.

EKG testing happened in 78.8% of men, compared with 74.2% of women versus 78.8% of men.

Only 12.4% of the women were admitted for observation, compared with 17.9% of men.

The study did not look into why women with chest pain are treated differently, and Banco said it’s more likely that outdated notions about risk, instead of overt discrimination, play a role. While heart attacks have historically been more common in older men, the rates are rising among women. But the lower rates of testing and admission could point to heart attacks that are being missed, she said.

She pointed to data showing a steady rise in heart attack rates among younger women over 20 years, with serious consequences. Compared to young men, “They have a higher mortality and poor physical and mental health after heart attack,” she said. “They’re less likely to return to work within 12 months after their heart attack.”

When a heart attack is suspected, minutes matter. Guidelines call for patients with a possible heart attack to have an EKG within 10 minutes of reaching the ER. “The longer people wait, the worse their outcomes can be,” Banco said.

The study will be presented May 15 during ACC, which will be in a virtual format for the second consecutive year due to COVID-19.

The study, which will be presented next week during the 70th American College of Cardiology Scientific Session, is the first to examine how chest pain is managed among adults who are too young for Medicare.

Fewer Tests, Longer Waits for Women in ER With Chest Pain

An FDA panel on Wednesday recommended keeping a pair of accelerated approvals in urothelial cancer, as regulators sort through what to do when cancer drugs reach the market based on early data, but follow-up studies tell a different story.


FDA’s Oncologic Drugs Advisory Committee (ODAC), recommended keeping indications for Tecentriq (azetolizumab), from Genentech, and for Keytruda (pembrolizumab), the immunotherapy that has proved a multipurpose blockbuster for Merck.

Early in the day, panelists voted 5-3 to retain Keytruda’s indication for first-line treatment in patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing therapy. Later in the day, the panel voted 10-1 to retain the same indication for Tecentriq, pending final overall survival (OS) results in a trial where panelists felt the data are not yet mature.

A day prior, a slightly different ODAC committee 

 to keep Tecentriq’s indication in metastatic triple negative breast cancer, after Genentech representatives said it would hard to replicate the trial that led to the accelerated approval. Complicating that vote was the fact that approval was based on using Tecentriq with nab-paclitaxel, but the confirmatory trial combined Tecentriq with paclitaxel and pretreated patients with steroids.

All three votes are the result of what some see as an evitable result of FDA’s accelerated approval pathway, which allows investigational drugs to reach the market based on phase 2 data, if the therapies might help some patients who lack treatment choices. The process calls for additional trials to confirm the results and keep the drugs on the market.

But as the two days of hearings have shown, once a drug is approved and in clinical guidelines, pulling it from the market is not so simple.

For each session, ODAC rotates in specialists who treat patients who might need the drug under review, and that reality weighed into their votes. For the Keytruda discussion, panelist Andrea B. Apolo, M.D., head of the bladder cancer section at the National Cancer Institute, said that while she prefers chemotherapy in a first-line setting, there are some patients who cannot receive it.

“Pembrolizumab is active as a second-line treatment for patients with platinum-refractory urothelial carcinoma, and I would argue that pembrolizumab is also active in the first-line treatment setting for patients that have PD-L1–high cisplatin-ineligible [disease],” she said. “As a treating medical oncologist and bladder cancer specialist, I vote to keep pembrolizumab available as a treatment option for patients in the first-line setting that are PD-L1 high.”

Susan Halabi, Ph.D., a biostatistician at Duke Cancer Institute, described her vote on Keytruda as “a very hard decision for me.” Trends toward longer overall survival (OS) and higher overall response rates seen in the second trial were consistent with early data, but the failure to confirm the early result was still “perplexing.”

In a statement, Merck’s Chief Medical Officer Roy Baynes, M.D., Ph.D., said, “The positive vote from today’s ODAC meeting supports the potential for Keytruda in certain patients with high-risk, non-muscle invasive bladder cancer, who currently have limited non-surgical treatment options approved by the FDA .We are encouraged by today’s productive discussion and look forward to working with the FDA as they continue their review of our supplemental application for KEYTRUDA in this patient population.”

In reviewing Tecentriq’s indication in urothelial carcinoma indication, panelists weighed an interim analysis of the confirmatory trial, which found the OS barely missing statistical significance. The study’s methodology states that if the drug falls short in meeting one benchmark others are not calculated, and this bogged the committee down for some time. In the end, most agreed that the best course was to keep the drug available for patients for now.

“There aren’t enough harms really to pull it and confuse patients and doctors,” Apolo said.

“Today’s positive vote reaffirms that Tecentriq fills a significant unmet need for people with previously untreated metastatic bladder cancer, many of whom cannot tolerate standard of care chemotherapy and need additional options,” Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development for Genentech, said in a statement. “Having now received positive ODAC recommendations in both bladder cancer and triple-negative breast cancer, we will continue to work with the FDA on next steps for Tecentriq in these indications.”

However, other data in a second-line trial in bladder cancer led to Genentech’s decision to voluntarily 

 for Tecentriq in March 2021. In doing so, 

 acknowledged that other treatments are now available for this particular group.

As hearings of the FDA panel have shown, once a drug is approved and in clinical guidelines, pulling it from the market is not so simple, even if later trials do not confirm phase 2 results.

Mary Caffrey

Articles

Biden Executive Order Takes Aim at Drug Prices, Hospital Mergers

In Urothelial Cancer, Most Subtypes Benefit From Maintenance Bavencio (Avelumab), Faltas Says

Fewer Tests, Longer Waits for Women in ER With Chest Pain

Two Approvals in Urothelial Cancer Survive FDA Panel Scrutiny