Team Biden ready to hand Russia and China vaccine technology — free of charge

 The Biden administration is about to give one of the biggest US technological breakthroughs of the 21st century to Russia and China — free of charge.

 
That’s not the administration’s goal, of course. But it’s the inevitable result of a proposed deal that US negotiators recently struck in Geneva, Switzerland, at the World Trade Organization.
 
The pact would effectively nullify intellectual-property protections on COVID-19 vaccines, including the next-generation mRNA shots from US companies Moderna and Pfizer. These mRNA platforms represent decades of research backed by billions of dollars in public and private investment. But if the WTO votes in favor at its summit starting June 12, our strategic and economic competitors — who contributed nothing to the effort — will enjoy the greatest free ride of all time.
 
It’s galling that the administration would cede the incalculable economic and diplomatic benefits from these platforms. And it’s particularly insulting that negotiators are telling their constituents the move is necessary to increase the supply of vaccines to the developing world. This is demonstrably false. 

In fact, there’s a global glut of vaccines — and that’s been the case for months. Late last year, five African nations — Malawi, Mozambique, Namibia, South Africa and Zimbabwe — asked Pfizer to halt vaccine shipments because they have more than they can process. Adar Poonawalla, CEO of India’s Serum Institute, says his company has 200 million doses sitting in storage due to a lack of demand. The Africa Centres for Disease Control and Prevention has requested a pause in vaccine donations.

Drug companies have the capacity to produce 20 billion COVID shots this year. That’s more than enough to serve a global population of about 8 billion people, many of whom have already been vaccinated. Supply is clearly not a problem.

The pact would void intellectual-property protections on COVID-19 vaccines.

Reuters/Mike Segar

So what is? Africa CDC head John Nkengasong says it’s partly a matter of logistics — having the staff and equipment necessary to get shots into arms — and partly vaccine hesitancy. Just as in wealthy parts of the world, many people in poor countries are skeptical about vaccines.

Suspending intellectual-property protections would do nothing to solve either of these on-the-ground barriers. It would, however, jeopardize the system that made COVID vaccines possible, along with countless other lifesaving medicines.

Drug manufacturers must invest billions of dollars to bring new medicines to market. The failure rate is high: Only 12% of experimental medicines that enter clinical trials are ultimately approved for patients. 

If innovators didn’t have a period of exclusivity over their drug designs, any rival could simply steal their work. No firm would be able to recoup its upfront investments into research — and funding for cutting-edge medications would plummet.

Proponents of the proposed deal dismiss these concerns, pointing out that it applies only to COVID vaccines, which of course already exist.

But that’s misleading. The language of the waiver is slippery. It states, “No later than six months from the date of this decision, [WTO] members will decide on its extension to cover the production and distribution of COVID-19 diagnostics and therapeutics.”

Note: “will decide,” not “may decide.” And waiver proponents are already pushing for this extension. “Vaccines are not the only tool in the fight against COVID-19,” says Initiative for Medicines, Access, and Knowledge co-founder Priti Krishtel. “To save as many lives as possible, an IP waiver would include tests and treatments.”

Africa put a halt on vaccine shipments because they had too many.

AFP via Getty Images

The waiver would set a disastrous precedent that activists and certain WTO members would surely try to expand to other areas of medicine. Why not waive patent protections on drugs that treat cancer and heart disease — two ailments that claim many more lives than COVID-19?

The waiver also poses a national-security risk. Russia would directly qualify for access to the mRNA technology. And China has pushed back against a footnote in the agreement designed to block the Communist nation’s access. Even if that footnote is ultimately approved, and China is technically barred from pilfering our technology, it could easily gain access indirectly with the help of its allies. In effect, the United States will unilaterally forfeit one of our few remaining economic advantages. American innovation will go to our biggest overseas competitor nations with zero compensation.

Violating the intellectual-property rights of US companies — and offering the fruits of their labor to our adversaries — is a spectacularly bad idea. That we’re poised to do so in the name of solving a vaccine shortage that doesn’t exist is mind-boggling.

Andrei Iancu served as the under secretary of commerce for intellectual property and US Patent and Trademark Office director from 2018 to 2021. David J. Kappos served in the same positions from 2009 to 2013.

https://nypost.com/2022/06/05/team-biden-ready-to-hand-russia-and-china-vaccine-technology-for-free/

Bionic Pancreas: Closer to Fully Automated Insulin Delivery?

 The investigational insulin-only iLet Bionic Pancreas (Beta Bionics) reduced A1c without increasing hypoglycemia in adults and children with type 1 diabetes with greater automation than currently available hybrid closed-loop or artificial pancreas insulin delivery systems.

Results from the pivotal multicenter Insulin-Only Bionic Pancreas Pivotal Trial were presented during a 1-hour symposium on June 3 at the American Diabetes Association (ADA) 82nd Scientific Sessions.

Automated insulin delivery systems comprise an insulin pump, a continuous glucose monitor (CGM), and a software algorithm connecting the two devices. The iLet pivotal trial is the largest randomized clinical trial to date of any automated insulin delivery system and enrolled a more diverse population of people with type 1 diabetes, including more from minority groups, and those with higher baseline A1c levels than in previous trials.

The data have been submitted to the US Food and Drug Administration (FDA), which granted the iLet a breakthrough device designation in December 2019.

The iLet differs from currently marketed artificial pancreas systems — the Medtronic 670G, Tandem t:slim X2 insulin pump with Control‑IQ technology, and the Omnipod 5 — in that users only enter their body weight to initialize the system with no run-in period prior to automation. The user signals meals in three quantity levels, without counting carbs or inputting the various mathematical settings currently required for insulin dosing.

"Other systems take a fair amount of initiation...whereas this one is automatically delivering insulin all the time. The input is just typical, larger, or smaller meals than usual. The system adapts...For most people, this system has potentially less burden," study coprincipal investigator and ADA session moderator Roy W. Beck, MD, PhD, told Medscape Medical News.

Asked to comment, Amar Puttanna, MBChB, told Medscape Medical News: "This just adds to the weight of evidence, and the move from data monitoring to intervention in terms of insulin delivery now. This [iLet] is the next stage, where we're working out [automated] insulin delivery...It's moving towards being the norm in the future."

"This shows regardless of ethnicity or social status or deprivation that there was benefit, so that highlights the importance of equality of care," noted Puttanna, consultant diabetologist in West Midlands, UK, and Sanofi national advisor for NHS engagement.

The bionic pancreas was initially conceived as a dual-hormone system using both insulin and glucagon in a single device to add greater protection against hypoglycemia. That is still the ultimate goal, but as of now a stable formulation of glucagon has only been approved for use as rescue for severe hypoglycemia and not for chronic daily administration, noted Beck, who is president and medical director of the Jaeb Center for Health Research Foundation, Tampa, Florida.   

"Glucagon is still coming. There's a lot to go through with FDA on the regulatory side to determine how much safety data is going to be needed. There haven't been any problems identified, but there has to be a lot more data collected than just to show that the device works, but that the glucagon given somewhat continually daily is going to be safe," Beck explained.

In the meantime, the company is moving forward with the insulin-only version.

Benefit Shown for Adults, Kids, Those With Higher A1c Levels

The insulin-only 16-center pivotal trial involved a total of 440 adults and children aged 6 years and older with type 1 diabetes. The study compared the iLet Bionic Pancreas to standard of care, which included about one third each on currently available artificial pancreas systems; stand-alone insulin pump and CGM devices; or multiple daily injections with CGM.

Participants were 74% White non-Hispanic, 10% Black non-Hispanic, 10% Hispanic or Latino, and 6% other or mixed race.  

The primary analysis compared the iLet using insulin lispro (Humalog) or insulin aspart (Novolog) versus standard of care in 326 adults and children, while the other 114 adults were in a separate arm that compared the iLet with faster-acting insulin aspart (Fiasp) versus the other two analogs.

Overall, after 13 weeks, average A1c dropped by 0.5 percentage points with the iLet compared to standard of care, and by 0.7 percentage points among participants with baseline A1c levels > 7.0%. There was no increase in hypoglycemia, and those using the device spent an average of 2.6 hours more time in range (glucose levels of 70-180 mg/dL).  

Among the 161 adults taking insulin aspart or lispro, mean A1c dropped from 7.6% at baseline to 7.1% at 13 weeks with the iLet versus to 7.5% with standard of care, a significant difference (P < .001). The proportions achieving A1c improvements of more than 0.5 percentage points were 43% with iLet versus 17% with standard care.

Overall, A1c improvements were greater in those with higher baseline A1c levels and were seen across racial groups and socioeconomic/educational levels.

After adjustment, adults using iLet spent 11% more time in range at 13 weeks, corresponding to 2.6 hours/day, compared with those on standard of care (P = .001).

Time spent with blood glucose levels below 54 mg/dL (hypoglycemia) at 12 weeks was 0.33% with the iLet and 0.18% with standard of care, which was not a significant difference (P = .33). Severe hypoglycemia occurred in 25.5 versus 14.2 events per 100 person-years, respectively, which was also not significant (P = .40). A total of 30 hyperglycemic events associated with infusion-set failures, a rate of 0.9% of 3203 infusion sets, occurred with the iLet.

Results were similar among the 165 pediatric subjects, with a drop in A1c from 8.1% to 7.5% with iLet versus no change from 7.8% in the standard care group.

Those using i-Let spent 10% more time in range at 13 weeks, corresponding to 2.4 hours/day, compared with those on standard of care (P < .001).

There were no differences in time spent below 54 mg/dL (P = .24). Here, the set failure rate was 3.0% for 3420 infusion sets.

Surprising That Fast-Acting Insulin Didn't Make Any Difference

The evaluation of the 114 adults using Fiasp versus lispro or aspart in the system showed no differences in A1c, mean glucose, time in range, or other parameters. That was a bit surprising, Puttanna said.

"There had been the question whether the Fiasp would have an impact. You want a fast-acting insulin, especially with the bionic pancreas because you want the algorithm to deliver the insulin without the need for carb counting when the bolus doses are given. So, you'd think theoretically you'd get a quicker response and the burden would be reduced. But it wasn't...Is it the system rather than the insulin, whereas in other systems fast-acting [insulin] might work better? We don't know," he said.

In surveys, the adults using iLet were significantly more likely than the standard care group to report reductions in diabetes distress and fear of hypoglycemia, and the parents of the children using the iLet reported greater increases in diabetes treatment satisfaction.

Give People What They Need

Ultimately, if approved the iLet could dramatically reduce type 1 diabetes management burden for many patients, but it might not suit everyone. For example, Beck said, "Somebody who's very compulsive and has an A1c of 6.5% and is used to manipulating what they do, this is probably not a good system for them because the system is kind of taking over."

Puttanna pointed out that if the dual-hormone iLet system [insulin and glucagon] ever becomes available that might represent a safety option for people with severe hypoglycemia or hypoglycemia unawareness.

The overall aim, he said, is to "give people what they need. You can tease out who needs what from the data and target with the right therapy — hybrid closed-loop, single or dual hormone, or maybe just real-time CGM."

And of course, he pointed out, in the United States cost and insurance coverage play a major role in who gets which devices.

This latest trial of a more automated system, he said, "shows where we're going, and that's exciting. We're almost there now [with full automation], which is fascinating and very encouraging. I hope it provides people with diabetes a lot of reassurance."

The trial was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk, and Beta Bionics. Beck has reported no disclosures. Puttanna is an employee of Sanofi (as of January 2022).

https://www.medscape.com/viewarticle/975060

Diabetes a Risk Factor for Long COVID? Possibly

 The jury is still out as to whether diabetes is a risk factor for post-acute sequelae of COVID-19 (PASC), a researcher reported.

In a scoping review of seven studies, three (43%) concluded that diabetes was indeed a "potent" risk factor for developing long COVID following infection, according to Jessica L. Harding, PhD, of Emory University School of Medicine in Atlanta.

Among these studies, diabetes was tied with more than a four times higher chance of developing long COVID symptoms, with all odds ratios settling over 4. These studies were mainly comprised of patients who were hospitalized for COVID-19 infection, she stated in a presentation at the American Diabetes Association (ADA) annual meeting.

However, in the four (57%) other included studies, the findings were inconclusive as to any significant links between diabetes and long COVID. For these studies, all ORs and relative ratios ranged between 0.5 to 2.2, and did not reach statistical significance.

"This review suggests there is some evidence that diabetes may be a potent risk factor for long COVID," Harding said, adding that results were ultimately limited by the small number of studies focusing on potential ties between diabetes and long COVID, along with the heterogeneity of the studies. In particular, there was a lack of a consistent definition of long COVID (although it generally was considered as ongoing symptoms of COVID such as fatigue, cough, dyspnea, and others); variance with regard to follow-up duration and risk adjustment; and differences in the at-risk populations included.

Harding explained that a 2022 Cell study inspired their research. That study found type 2 diabetes was one of four significant risk factors for developing long COVID, and also reported that SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies were strong risk factors for post-acute sequelae of COVID-19.

"More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for long COVID," Harding's group stated. "In the meantime, while we wait for that data, careful monitoring of people with diabetes for the development of long COVID is advised."

For the review, they looked at 39 studies published from January 2020 to January 2022 that included a minimum of 4-weeks of follow-up after a COVID-19 diagnosis. All studies also compared the incidence of long COVID in people with diabetes versus patients without.

The seven studies included in the analysis had a longitudinal cohort design and had adults from high-income countries, such as Italy, Norway, U.S., U.K., and Sweden. The largest study followed 4,182 patients.

There was a mix of hospitalized and non-hospitalized patients with COVID, as well as patients with other comorbidities such as kidney transplant recipients. That study of kidney transplant recipients with COVID-19 found a 4.42-times higher odds of long COVID with diabetes (OR 4.42, 95% CI 1.16-16.8).

Disclosures

The study was supported by the National Heart, Long, and Blood Institute.

Harding disclosed no relationships with industry. Co-authors disclosed relationships with Bayer and Merck.

Primary Source

American Diabetes Association

Source Reference: Harding JL, et al ""Diabetes as a risk factor for long-COVID-19 - a scoping review" ADA 2022; Abstract 174-LB.

https://www.medpagetoday.com/meetingcoverage/ada/99066

Complete Responses in 100% of dMMR Rectal Cancer With Neoadjuvant PD-1 Inhibition

 Single-agent dostarlimab (Jemperli) led to complete responses in 100% of a small group of patients with locally advanced mismatch repair-deficient (dMMR) rectal cancer, allowing them to avoid surgery, chemotherapy, and radiation, at least for the time being.

All 14 patients followed for at least 6 months had clinical complete responses with no evidence of tumor on follow-up MRI. Follow-up in the cohort range from 6 to 25 months, and none of the patients have received additional therapy. Four other patients with limited follow-up have preliminary evidence of response, including one clinical complete response.

The 6-month course of the PD-1 inhibitor was well tolerated, and no patient developed grade ≥3 adverse events, reported Andrea Cercek, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York City, at the American Society of Clinical Oncology (ASCO) annual meeting. The study was published simultaneously in the New England Journal of Medicine.

"We observed 100% complete response in the first 14 consecutive patients," said Cercek. "We noted no grade 3 or 4 adverse events. No patients have required chemotherapy, radiation, or surgery. There has been no disease recurrence during the follow-up period. Longer follow-up is certainly required to establish the durability of this treatment."

"This data provides the framework for immunoablative therapies and highlights the clinical impact of biomarker-drive therapy in early-stage disease," she said. "The tumor-agnostic mismatch repair-deficiency population of early-stage disease has the potential to eliminate the need for chemotherapy, radiation, and surgery in 3%-4% of all cancers. This has the potential to be translated rapidly into areas around the world without access to modern chemotherapy, radiation, and surgery."

Not Yet Practice Changing

The results are clinically meaningful and scientifically plausible but cannot be considered practice changing at this point, said ASCO invited discussant Kimmie Ng, MD, MPH, of Dana-Farber Cancer Institute in Boston.

"My answer is 'not yet' for several reasons," said Ng. "The sample size is still relatively small. The median follow-up is still extremely short with a median of 6.8 months. We know from the OPRA trial that 88% of tumor regrowth can happen up to 2 years after completion of TNT [total neoadjuvant therapy]. All patients were enrolled at a single institution [MSKCC], which arguably has the most extensive expertise in nonoperative management of rectal cancer."

"Finally, the only endpoint available right now is overall response, with no data on survival or other clinically relevant outcomes," she noted.

Ideally, unresolved issues about the treatment would be addressed in a randomized clinical trial (RCT), comparing neoadjuvant dostarlimab with standard TNT. However, such a trial is unlikely, said Ng. The condition is rare, reflected in the 29 months required to accrue 18 patients. Off-protocol use of neoadjuvant immunotherapy is likely to occur following publication of the dostarlimab results. As news of the results circulate, patients' willingness to be randomized in a clinical trial is questionable.

In the absence of data from a RCT, more patients and longer follow-up on other clinically relevant endpoints, such as 3-year disease-free survival, overall survival (OS), and organ preservation, are needed.

"Importantly, we need multi-institutional participation," said Ng. "We need to confirm the high clinical complete response rates and that the complex nonoperative management of rectal cancer can be replicated in all cancer care settings."

Study Background, Results

Standard of care for locally advanced rectal cancer consists of chemotherapy, radiation, and surgery. Recent studies have provided support for neoadjuvant chemotherapy followed by chemoradiation and surgery, said Cercek. The strategy produces pathologic complete response in as many as a fourth of patients but is associated with potentially severe complications and toxicity.

Given the life-altering impact of surgical resection of the rectum -- which often requires a permanent colostomy -- interest in organ sparing, nonoperative treatment has increased, Cercek continued. Clinical complete response to neoadjuvant treatment as a surrogate for pathologic complete response offers patients a nonoperative option that leads to survival benefits similar to those observed with surgery.

From 5%-10% of rectal adenocarcinomas are dMMR and typically respond poorly to standard chemotherapy. Single-agent checkpoint inhibition has produced response rates of 33%-55% in metastatic dMMR colorectal cancer, and responses have often been durable, leading to prolonged OS. On the basis of those results, investigators hypothesized that single-agent anti-PD1 treatment might be beneficial in dMMR locally advanced rectal cancer.

Dostarlimab initially received FDA approval for recurrent or advanced dMMR endometrial cancer. More recently, the FDA granted a tissue-agnostic approval to the PD-1 inhibitor for recurrent/advanced dMMR solid tumors that have progressed on prior therapy and have no suitable alternatives.

Cercek reported updated findings from an ongoing phase II trial to evaluate the frequency and durability of responses to neoadjuvant dostarlimab. A preliminary report from the study showed that the first 11 patients treated had complete responses. Investigators plan to enroll a total of 30 patients with stage II/III dMMR rectal cancer.

The primary objectives are overall response rate with single-agent dostarlimab with or without chemoradiation and pathologic complete response or clinical complete response at 12 months after PD-1 inhibition with or without chemoradiation. Rectal MRI and endoscopy determine stable disease, and response (partial, near complete, and complete). Clinical complete response is defined by endoscopy, digital rectal exam, and rectal MRI.

The first 18 patients had a median age of 54, and women accounted for 12 of the patients. Fourteen patients have T3/4 tumors, and all but one patient had one or more involved lymph nodes. Ten of 17 evaluable patients had germline mutations, and all 18 patients had BRAF V600E wild-type tumors.

In the first 14 patients, clinical complete response occurred at the 6-month follow-up in 12 patients, and two met criteria for complete response by 3 months. The four remaining patients had not reached 6 months of follow-up, but one patient had already met criteria for clinical complete response.

Disclosures

The study was supported by MSKCC, Tesaro/GlaxoSmithKline (GSK), Simon and Eve Colin Foundation, Stand Up to Cancer, Swim Across America, and the National Cancer Institute.

Cercek disclosed relationships with Bayer, GSK, Incyte, Janssen, Merck, Seattle Genetics, and Rgenix.

Ng disclosed relationships with Bicara Therapeutics. BiomX, GSK, redesign Health, Seattle Genetics, X-Biotix Therapeutics, Evergrande Group, Janssen, Pharmavite, and Revolution Medicines.

Primary Source

American Society of Clinical Oncology

Source Reference: Cercek A, et al "PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer" ASCO 2022; Abstract LBA5.

Secondary Source

New England Journal of Medicine

Source Reference: Cercek A, et al "PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer" N Engl J Med 2022; DOI: 10.1056/NEJMoa2201445.

https://www.medpagetoday.com/meetingcoverage/asco/99071

Amgen drug extends survival in some inoperable colon cancers

 

The following are summaries of some of the cancer research advances being presented the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

Amgen drug extends survival for some advanced colon cancers

Amgen Inc's drug Vectibix led to "the longest survival ever reported" in a major trial for patients with inoperable advanced cancer originating on the left side of the colon whose tumors did not have RAS gene mutations, researchers reported on Sunday at ASCO 2022 https://meetings.asco.org/2022-asco-annual-meeting/14416?presentation=208990#208990.

Amgen's monoclonal antibody, known chemically as panitumumab, belongs to a class of drugs called EGFR inhibitors. The standard treatment in many countries, however, is an anti-VEGF antibody like Roche's Avastin, which means many patients with inoperable metastatic cancer may not have been getting the most effective treatment.

In the trial of more than 800 patients with metastatic colon cancer and the "wild-type," or natural non-mutated, RAS genes, participants received standard chemotherapy plus either Vectibix or Avastin. An average of five years later, patients with right-side tumors did not see a survival advantage for one drug over the other. But among the 604 patients with left-side tumors, the risk of death during the study was 18% lower for those who got Amgen's drug, researchers said.

Patients treated with the anti-EGFR drug were more likely to see their tumors shrink enough to be eligible for potentially curable surgery, study leader Dr. Takayuki Yoshino of National Cancer Center Hospital East in Kashiwa, Japan, said in an interview, adding that this treatment "should be the new standard of care."

Delaying cell transplants for multiple myeloma appears safe

Younger patients with newly diagnosed multiple myeloma who delay a stem cell transplant do not have shorter survival than those who undergo transplant promptly, and modern drug regimens may allow them to avoid the procedure entirely, according to research presented on Sunday https://meetings.asco.org/2022-asco-annual-meeting/14416?presentation=213607#213607.

On average, patients who had early transplants went more than 67 months without their disease worsening versus 46 months for those who delayed their transplants. But overall survival rates in both groups were the same, even though only 28% of patients in the delayed group eventually had a transplant. Others in that group were able to change treatments.

Participants in the 722-patient trial provided their own stem cells to be stored and reinfused during a transplant. Half then underwent transplantation before receiving multiple cycles of a three-drug protocol that included Bristol Myers Squibb's Revlimid - long the standard multiple myeloma treatment - followed by Revlimid maintenance therapy. The rest received the three-drug protocol followed by maintenance therapy until medications stopped working and transplant was the only option.

Stem cell transplants are grueling and can have serious side effects but remain the standard of care, study leader Dr. Paul Richardson of the Dana Farber Cancer Institute in Boston said in an interview. Doctors can now tell patients: "You've got choices. We can treat you with triple-drug therapy and see how you do, and you can keep transplant in reserve."

Data show best drug for deadly childhood cancer

In the first randomized trial comparing treatments for relapsed or treatment-resistant Ewing's sarcoma, a rare and deadly childhood cancer, high-dose ifosfamide (IFOS) produced the best results, allowing patients to live about five months longer, according to data presented on Sunday at ASCO.

Ewing's sarcoma occurs in only about 200 U.S. children a year. In roughly 30% to 40% of patients, it resists treatment or recurs. These patients have a five-year survival rate of just 15%. The nine-country study involved 451 patients. Initial participants were randomly assigned to receive one of four common chemotherapy regimens. The two least effective were dropped from the study and later patients received one of the remaining two - IFOS or topotecan and cyclophosphamide (TC).

Median event-free survival - the average time patients went before disease worsening, emergence of a second cancer or death - was 5.7 months for IFOS versus 3.5 months with TC. Overall survival was 15.4 months with IFOS vs 10.5 months with TC, while one-year survival rates were 55% vs 45%, respectively.

Study leader Dr. Martin McCabe of the UK's University of Manchester called the results "relatively strong data," but noted that IFOS is toxic. "And all of these patients still die. We need better medicines."

https://www.marketscreener.com/quote/stock/AMGEN-INC-4847/news/Amgen-drug-extends-survival-in-some-inoperable-colon-cancers-40646575/

New data sets stage for broader use of AstraZeneca breast cancer drug

 AstraZeneca and Daiichi Sankyo’s Enhertu extended survival by more than six months in patients with a form of advanced breast cancer compared to standard chemotherapy, according to data presented on Sunday.

The data, unveiled at the American Society of Clinical Oncology (ASCO) meeting in Chicago, could open a large, new multibillion-dollar patient population for the drug that won U.S. approval in late 2019 as a third-line treatment for the 15% of breast cancer patients with HER2-positive disease

The ongoing phase III trial involves over 550 patients with so-called HER2-low breast cancer – most with tumors that were hormone-sensitive – whose disease had spread and had undergone at least one round of chemotherapy.

The interim analysis showed Enhertu prolonged survival by an additional 6.4 months in patients with hormone-sensitive tumors. Patients in the group lived for a median of 23.9 months versus 17.5 months for chemotherapy.

In the small group of patients with hormone-insensitive tumors, patients on Enhertu lived 6.3 months longer.

That the benefit in overall survival was apparent even at the point of interim analysis was surprising, David Fredrickson, executive vice president of AstraZeneca’s oncology unit, told Reuters.

“That really puts a lot of confidence that the benefit that we’re seeing here is absolutely real.”

A host of targeted therapies has greatly improved the prognosis for patients with advanced HER2-positive breast cancer. But more than half of women whose breast cancer has spread to other organs and express little or no HER2 – referred to as HER2-low status – have limited treatment options.

Hormone-sensitive patients who received Enhertu also went an average of 10.1 months before their disease began to worsen – a measure known as progression free survival (PFS) – compared with 5.4 months for chemotherapy, which was statistically significant.

Enhertu more than doubled the PFS for hormone-insensitive patients at 6.6 months versus 2.9 months for chemotherapy.

AstraZeneca is in discussions with regulators globally for approval in the HER2-low population. Jefferies analysts last month forecast $2.5 billion in annual global peak Enhertu sales for these patients, and about $6.6 billion across all indications.

The drug, which is administered as an intravenous infusion, is not without safety concerns. It has been linked to a type of lung scarring called interstitial lung disease (ILD). Forty-five Enhertu patients in the trial had varying degrees of ILD versus one in the chemotherapy group.

Enhertu belongs to class of therapies called antibody drug conjugates (ADC), which are engineered antibodies that bind to tumor cells and release cell-killing chemicals.

Last month, it gained approval as a second-line treatment option after a study showed it reduced the risk of disease progression or death by 72% compared to Roche’s Kadcyla, which has been the standard treatment.

Enhertu is being evaluated for use in earlier stages of breast cancer, as well as lung and colorectal cancers, among others. It has secured approval in HER2-driven gastric cancer.

“As far as breast cancer goes, I’d say at least in the next few years, I’m pretty sure in Enhertu is going to kind of finish revolutionizing the treatment paradigm,” Tara Hansen, a consultant at Informa Pharma Custom Intelligence, told Reuters.

Enhertu had sales of $214 million in 2021. AstraZeneca secured partial rights to the Daiichi Sankyo compound three years ago in a deal worth up to $6.9 billion.

https://thefifthskill.com/new-data-sets-stage-for-broader-use-of-astrazeneca-breast-cancer-drug/

The end of retirement as we know it?

 Picture retirement in your head. It’s a laughing, grey-haired couple sipping piña coladas on a white sand beach; perhaps they’re getting some liquid courage for their sky dive later. Not a care in the world, their only responsibility is getting their grandchildren good gifts for their birthdays. It’s a beautiful fantasy – and for many retirees, present and future, it’s just that: a fantasy. 

The concept of retirement as we know it is changing, and has been for a long time. The number of people working past retirement age has grown consistently since the 1990s. In the US, 32% of people aged 65 to 69 were in work in 2017, far more than the 22% who were working in 1994. In the UK, employment rates for people older than 65 doubled between 1993 and 2018.

Then came Covid-19. “Society was already poised for a real shift in how it’s thinking about retirement,” says Michelle Silver, associate professor of gerontology at the University of Toronto Scarborough. “But the pandemic has definitely exacerbated it.”

When the pandemic hit, labour trends went awry. First, there was an exodus of older professionals from the workforce; in the UK, at least an extra 250,000 50- to 64-year-olds left, while more than 3 million Americans retired early.

Now, however, as inflation spikes, the number of people coming out of retirement is growing. In the US, job site Indeed reports 'unretirement' levels are at 3.3%, much higher than the sub-3% average seen since 2017. In the UK, Indeed saw a spike in 55-to-64 year-olds ‘urgently seeking work’, while another survey found that two-thirds of people who retired during the pandemic expect to keep working in some form.

Gaëlle Blake, UK and Ireland director for permanent appointments at recruitment firm Hays, says she believes “this is the start of a phenomenon where people are feeling the pressure financially, so they will come back to work”. Whether that’s part-time, full-time or a side gig, people are increasingly expecting and needing to work past traditional retirement age – perhaps permanently reshaping our idea of what this life stage might look like

In many cases, older workers with specific skills are being called back by former companies to plug knowledge gaps (Credit: Getty Images)

‘Our savings have gone down’

While there are several factors behind retirees’ return to the workforce, it’s clear that concerns linked to the cost of living are currently a major motivator. In the UK, of the over-50s who have returned to work since leaving during the pandemic, 48% said they did so because they needed money, while 23% said they couldn’t afford to retire. 

Blake says she’s seen retirees’ positions change dramatically during the pandemic. Early on, they were leaving the workforce in droves, partly due to fears linked to Covid-19, but also to do with their assets; house prices started soaring, and investments were up. “It would have meant their pension programmes were very high, their houses were valued very high.” But now, she says, inflation means people don’t feel as comfortable as they did a year ago. “People are definitely wanting to come back to work.”

It’s a similar story in the US. Anthony retired from his job at a shipping multinational in January 2020. He took his package early, in his late 50s, because he was tired of working for corporate America and a boss he didn’t like. But his retirement plan didn’t account for historic inflation increases. “Everything that we had planned for the future was based on having X amount invested,” he says. “But this year has been such a correction, our savings have gone down 20%.” 

Luckily for Anthony, he had already re-joined the workforce when his investments started to drop, and the cost of living began to rise. A year into the pandemic, his former company called him, told him his old boss was gone and asked if he wanted to come back to work on a project. 

“The deal is they’re paying me basically the same salary as I was making. And that’s on top of my retirement [pension],” says Anthony. He believes they brought him back to plug a skills shortage. “Whenever you have mass exodus from a company, you lose knowledge,” he says. “Sometimes you need fresh blood to get new ideas. But sometimes, to get things done quickly, you need older blood that knows how to get it done. And I’m in that latter half.”

It’s really important to recognise that retirement is just a phase that was invented, it’s not a natural progression or an essential stage of life – Michelle Silver

Many retirees are being courted by companies with skilled vacancies to fill. In the UK, the unemployment rate is 3.7%, the lowest it’s been in 50 years. “But there’s also a record number of jobs,” says Blake. “So, you’ve got no talent pool.” She says the people who’ve chosen to retire are exactly the people that are needed in the labour market – knowledge workers like teachers, nurses, doctors, surveyors, technology professionals. “Where there is demand, they have the matching skill set,” says Blake. “They are the missing people.”

In the US, where unemployment is the lowest it’s been since the 1960s, unretirement is being touted as a solution to a raft of labour shortages – and many retirees are on board. Richard Sartiano retired from a medical device company in April 2021, but only a few months later – motivated by both rising living costs and boredom – he was job hunting again.

“I wanted to do something productive,” says Sartiano. “One of my children suggested I take up painting.” Instead, he applied for a director position at Purdue University, Indiana. “I wanted something challenging,” he says. “I have a pretty good education and I still want to use it.” Just a year after retiring, Sartiano had a new, full-time job.

Flexible retirement

While returning to full-time employment may work for some older workers, other retirees are seeking more flexible employment. In the UK, of the 50-to-70-year-olds who left the workforce during the pandemic, 69% of those looking to come back want to work part-time – planning a semi-retirement, rather than a fully-fledged one.

New Jersey-based Richard Eisenberg, who started his semi-retirement from journalism in January 2022, divides his time among writing part-time and volunteering, mentoring and experimenting with new challenges he didn’t have time for when he was in full-time work. Eisenberg says he’s “glad to have the extra income”, because the possibility of running out of money is always a back-of-the-mind concern, even though he and his wife have built up solid pension pots. But he’s also keen to keep working for mental stimulation. “I’m not somebody who plays golf,” he says, “so I just felt like if I wasn’t going to be doing some kind of work, I wouldn’t know what to do with myself. And I would get pretty bored, possibly depressed, and I didn’t want that to happen.”

Instead of taking on full-time jobs, some retirees are opting for more flexible, part-time work (Credit: Getty Images)

Unhappiness in retirement is a well-documented issue. Silver, of the University of Toronto Scarborough, says retirement can be “an incredibly dissatisfying experience” for those whose personal and work identities are intertwined. She suggests the pandemic offered many people a preview of retirement - being with your partner all day, or alone all day, without the traditional structures of work – and that some people who traditionally would have retired by now realised the lifestyle didn’t appeal to them.

Plus, as flexible work practices increasingly become the norm, it’s become much easier to continue to do some work from a retirement setting – as Annie Llewellyn discovered. She retired 10 years ago, after a career as a university lecturer. “The first year, I really enjoyed it,” she says. “But then I realised, I didn’t have enough money to really support myself.” So, she took on freelance work, such as marking papers and giving lectures. “Now I really enjoy the flexibility of having a retirement income plus a job,” says Llewellyn, who lives between Italy and a shared house in Wales.

Since the pandemic has accelerated the adoption of more flexible working practices, Llewellyn has found it much easier to maintain her unretired lifestyle. “Coronavirus changed the world of homeworking,” she says. “I don't work full time by any means, I wouldn't want that, but I think it's a new stage of life.”

A natural progression?

If current cost-of-living concerns ease, it’s possible that some older workers will no longer feel the need to be employed past retirement. But general trends – we’re living and working longer, and many of us aren’t saving adequate pension pots – suggest that ‘retirement’, for many, will include working in some form.

The shift to flexible work, however, could benefit both today’s retirees and also the younger workers lamented as the generations who will never be able to afford to retire. Before, the wealth gap between boomers and later generations might have meant many people toiling away at their desks well into their 70s.

But flexible working offers a new option – a different version of the beachy retirement fantasy. Last week, Llewellyn took a weekend trip to Corfu with a friend. “I was working for a few hours, but I was swimming, too,” she says.

This flexible version of retirement won’t be available to everyone, but it is an indicator of how the concept itself can and should evolve. “I think it’s really important to recognise that retirement is just a phase that was invented, it’s not a natural progression or an essential stage of life,” says Silver. “I think that now, lots more people will questions what it means, and whether it is really a life goal for everyone.”

https://www.bbc.com/worklife/article/20220526-is-this-the-end-of-retirement-as-we-know-it