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Wednesday, October 5, 2022

AnaptysBio / GSK-Partnered Immuno-Oncology Agent Meets Primary Goal In Lung Cancer Trial

 

  • AnaptysBio Inc  - GSK plc  partnered PERLA head-to-head trial of Jemperli vs. Keytruda for metastatic non-squamous non-small cell lung cancer, met its primary endpoint of objective response rate (ORR).
  • GSK expects to present full results from the PERLA trial, including the primary endpoint of ORR and the key secondary endpoint of progression-free survival, with results by programmed death ligand-1 (PD-L1) expression subgroups, at an upcoming scientific meeting.
  • The trial evaluated dostarlimab plus chemo versus Merck & Co Inc's  Keytruda (pembrolizumab) + chemo.
  • The trial was not designed to demonstrate superiority. 
  • AnaptysBio also announced that GSK is advancing both arms of the COSTAR Lung Phase 3 trial from Phase 2 to Phase 3, testing doublet and triplet combinations of dostarlimab plus chemo and cobolimab plus dostarlimab plus chemotherapy in advanced NSCLC. 
  • This decision follows the recommendation of the trial's Independent Data Monitoring Committee.
  • AnaptysBio expects to receive a $5 million milestone payment from GSK upon dosing the first patient with cobolimab in the Phase 3 portion of COSTAR.

Eiger BioPharma Shuns Plans For FDA Emergency Use Nod For COVID-19 Treatment

 

  • Following FDA feedback, Eiger BioPharmaceuticals Inc (NASDAQ: EIGRwill not submit an emergency use authorization (EUA) application of peginterferon lambda for mild-to-moderate COVID-19.

  • Following Eiger's press release in September, the company submitted a pre-EUA meeting request to FDA, as well as additional morbidity and mortality outcomes data and analyses from the investigator-sponsored TOGETHER study.

  • FDA denied the request for a pre-EUA meeting. Citing its concerns about the conduct of the TOGETHER study, FDA concluded that any authorization request based on these data is unlikely to meet the statutory criteria for issuance of a EUA in the current context of the pandemic.

  • FDA suggested that Eiger consider requesting an end-of-Phase 2 meeting to discuss a company-sponsored pivotal trial that could support an eventual Biologics License Application (BLA).

  • Eiger is evaluating the next steps for this program in the U.S., as well as ex-U.S. emergency use authorization pathways and strategic options for continued development of peginterferon lambda for COVID-19 and other respiratory viral infections.

GSK’s Jemperli Stands Up in Phase II NSCLC Trial

 GSK reported Wednesday that its checkpoint inhibitor Jemperli, which made headlines earlier this year in rectal cancer, yielded positive data in non-small cell lung cancer, moving the monoclonal antibody potentially closer to the market in this indication.

Researchers at Memorial Sloan Kettering Cancer Center unveiled data in June on 14 patients who received Jemperli as a first-line treatment for MMRd locally advanced rectal cancer. In the study, all 12 patients who completed treatment went into remission.

GSK said Jemperli, a PD-1 inhibitor known generically as dostarlimab, met its main goal of an objective response rate in the Phase II PERLA trial assessing the drug in NSCLC. It also yielded positive, progression-free data. Jemperli was tested in combination with chemotherapy against Merck's best-selling Keytruda plus chemotherapy.

PERLA enrolled 243 patients. The most common side effects were anemia, asthenia, nausea, constipation, cough and other expected adverse effects.

The trial was not designed to determine whether Jemperli is superior to Keytruda, GSK stated in its announcement. Instead, it endeavored to show its potential as a treatment option for NSCLC.

GSK announced it is advancing Jemperli into a two-armed, Phase III clinical trial for lung cancer patients based on data reviewed by an independent data monitoring committee. That trial is testing Jemperli in various combinations with other monoclonal antibodies and traditional chemotherapy.

GSK spokeswoman Lyndsay Meyer told BioSpace company scientists would present the data at an upcoming scientific conference, likely by the end of the year. She declined to disclose which conference.

“These trials support the ambition for dostarlimab to become the backbone of our ongoing immuno-oncology-based research and development program when used alone and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options,” said Hesham Abdullah, global head of oncology development at GSK said in a statement.

The FDA approved Jemperli in 2021 to treat a small subset of adult patients with mismatch repair-deficient recurrent or advanced solid tumors - mostly endometrial cancer patients with hard-to-treat tumors.

https://www.biospace.com/article/gsk-s-jemperli-stands-up-in-phase-ii-nsclc-trial/

Biohaven Sets New Course Following Pfizer Acquisition

 Biohaven Pharmaceuticals has set a new course following its acquisition by Pfizer with a focus on developing therapeutics that modulate the Kv7 Ion Channel for the treatment of neurological and neuropsychiatric diseases.

The company officially launched Tuesday as a new spin-off entity with more than 13 clinical and preclinical programs. Biohaven’s primary focus will be developing treatments for neurological and rare disorders including epilepsy, pain and mood disorders, obsessive-compulsive disorder, spinocerebellar ataxia and spinal muscular atrophy.

The new Biohaven launches with approximately $257.8 million in cash.

The seeds for this new path were established earlier this year with the acquisition of Channel Bio, a subsidiary of Knopp Biosciences. This brought in the experimental epilepsy treatment BHV-7000, which targets the Kv7 ion pathway. BHV-7000 is currently in Phase I development for multiple indications.

Biohaven Chief Executive Officer Vlad Coric told BioSpace the future looks bright for the new phase of the company. He noted that the drugs targeting the Kv7 ion pathway will be the centerpiece of the company. Coric explained that previously conducted studies showed the efficacy of this approach in treating epileptic seizures.

"That makes for a de-risked mechanism," he said. "We believe this (BHV-7000) has the potential for best-in-class."

Additionally, the company licensed rights to an experimental spinal muscular atrophy drug from Bristol Myers Squibb. That asset, an anti-myostatin adnectin, is expected to enter late-stage development later this year.

Coric said this drug is intended to work alongside existing gene therapies for SMA, such as Novartis' Zolgensma. He said the gene therapy can halt and reverse the disease, while the former BMS asset will assist by helping rebuild lean muscle mass in children. 

The new company will continue to be helmed by Coric as chairman and CEO officer. Other established members of the leadership team include Irfan Qureshi as chief medical officer, and Tanya Fischer, who serves as chief development officer and head of translational medicine.

Bruce Car joins the company as chief scientific officer. Car most recently served as CSO of Agios Pharmaceuticals where he focused on genetically defined diseases and oncology. He previously held leadership roles at BMS and Dupont.

A New Therapeutic Focus

Biohaven will focus on developing therapeutics based on its proprietary technology platforms. This includes BHV-7000, a lead program in Kv7 Ion Channel Modulation for epilepsy and other central nervous system disorders associated with pathological hyperactivity.

BHV-7000 is being assessed for the treatment of KCNQ2 developmental and epileptic encephalopathy, a rare and debilitating disease that manifests in infants and children as early-onset seizures. It is also being studied for encephalopathy due to a defect in the function of the Kv7.2 channel caused by pathogenic mutations in the KCNQ2 gene. 

Kv7 Ion Channel Modulation targets subunits involved in neuronal signaling. It also plays a role in regulating the “hyperexcitable state” in epilepsy and could potentially play a role in other central nervous system disorders. 

In its announcement, Biohaven pointed to multiple clinical development programs that include Glutamate modulation for spinocerebellar ataxia and obsessive-compulsive disorder. Coric said the OCD treatment has compelling proof-of-concept.

The company also has a program aimed at the inhibition of myostatin in neuromuscular diseases. Not only can this play a role in SMA, Coric said it could play a role in diabetes and weight loss.

Biohaven is also developing a novel immune modulation platform that targets CD-38 for multiple myeloma.

Biohaven’s initial focus will be to advance Kv7 ion channel activation across multiple therapeutic indications, as well as TRPM3 ion channel activation for neuropathic pain. The company also intends to develop degrader platforms that target immunology and oncology inflammatory disorders and antibody linker technologies.

Beyond these, Biohaven is keeping an eye on potentially targeting disease adjacencies, which can include pain, smooth muscle disorders and immunological disease, according to the Tuesday statement.

Biohaven’s experimental ALS treatment verdiperstat, which recently missed the mark in the Healey ALS trial, was not mentioned. When the data was announced last week, Biohaven reported it would continue to assess the trial information. Coric reiterated that today and said the company will reassess what they do with the asset after the data is compiled. 

Pfizer Retains 3% Stake 

Under terms of the Pfizer acquisition, the pharma giant retains Biohaven’s calcitonin gene-related peptide (CGRP) receptor antagonist products, which includes Nurtec ODT, a treatment for acute and episodic prevention of migraine in adults. Additionally, Pfizer will hold onto the potential migraine treatment zavegepant, which has been submitted to the FDA for potential approval. A PDUFA date has not yet been set. Pfizer will also retain a portfolio of pre-clinical CGRP assets.

Even as Biohaven sets a new course as an independent company, Pfizer will retain a 3% investment in the new entity.

https://www.biospace.com/article/biohaven-sets-new-course-with-a-focus-on-neurological-neuropsychiatric-diseases-/

Tuesday, October 4, 2022

How tight nursing home capacity is bottlenecking hospital operations

 A lack of capacity in nursing homes is hurting hospitals’ ability to discharge their patients, giving rise to steadily increasing lengths of stay and stressing systems as they attempt to navigate a precarious operational environment coming out of the COVID-19 pandemic.

A Healthcare Dive review of recent financial filings found that even as overall inpatient admissions fell, large hospital operators reported longer lengths of stay, along with difficulties discharging patients, compared to prior years. That trend was evident across both nonprofit and for-profit operators, and contributed to waning operational income for many systems.

“What we’re seeing is more organizations have inpatient discharges that are below what the pre-pandemic level was, but the patient days they’re staying is not depressed,” said Erik Swanson, senior vice president of data analytics at Kaufman Hall. “We’ve seen continual growth in length of stay since the beginning of the pandemic up to now.”

ProvidenceIntermountainSutterMass General Brigham and Advocate Aurora — all large nonprofits — are among the systems that reported higher lengths of stay and lower discharges this summer compared to 2021.

For-profit operators HCA Healthcare and UHS also reported year-over-year increases in lengths of stay in the second quarter: from 4.94 days to 4.99 days, and from 4.8 days to 4.9 days, respectively.

Longer lengths of stay are contributing to some of the worst hospital margins seen since the beginning of the pandemic and a deteriorating sector outlook from ratings agencies.

That’s in part because Medicare, which covers a large part of the inpatient population, generally pays for an inpatient’s hospital stay by a diagnostic-related group (DRG), or one fixed amount based on their diagnosis and severity — regardless of how long they’re in the hospital. Other private payers often pay a flat rate as well for certain expensive inpatient stays, such as bundled payment models for total joint replacements or heart attacks.

As a result, the longer a patient stays, the higher the cost to the hospital, said Rick Gundling, senior vice president of healthcare financial practices for the Healthcare Financial Management Association.

“They generally lose money anyway, it just widens the loss,” Gundling said.

A ‘massive and urgent’ need for labor

A number of facilities said the increasing length of stay was due to problems discharging patients to other care settings. Roughly 12% of all inpatients are discharged to some form of long-term care facility like nursing homes, which were already stressed before the COVID-19 pandemic. But the pandemic’s operational pressures walloped the cash-strapped facilities, leading to a spate of resident deathsstaff shortages and closures.

Providence, one of the largest nonprofits in the U.S., said discharges to skilled nursing facilities have proved most challenging, especially in states with chronic deficiencies in available beds that’s now compounded by a declining workforce.

That’s creating a backlog in acute care — Providence had an average length of stay of 5.85 days in the first six months of the year, compared to 5.62 days in 2021.

“We feel this problem requires some level of intervention by state and federal authorities to create the necessary relief in service to our communities. The need is massive and urgent,” a spokesperson for the system said.

As of August, nursing home employment was down 10% from its peak in January 2020, before the COVID-19 pandemic hit the U.S., according to Bureau of Labor Statistics data.

That’s a large decline compared to the labor recovery seen in other sectors. Hospital jobs are just a shade below pre-pandemic levels, while employment in physician offices and the ambulatory care and home health sectors have bounced back and are even outperforming overall private sector employment, according to a Center for Health Workforce Studies analysis of government data.

Nursing home workforce recovery lags behind that of peers

Relative number of employees by sector, January 2020 to August 2022 (Jan. 2020 = 1.00)

“There’s no beds. Or no staff — even if there is a bed, there may be no staff. So hospitals can’t discharge,” Gundling said.

There’s a variety of reasons that nursing homes — especially skilled nursing facilities — have seen a downward trend in employment, said Bianca Frogner, a health systems and population health professor at the University of Washington School of Public Health.

The larger movement toward home- and community-based services is shifting business away from traditional post-acute care settings, and the spread of COVID-19 in nursing homes during the pandemic raised alarms about safety and security at facilities, according to Frogner. In addition, nursing homes have difficulty raising wages, especially those that rely heavily on fixed Medicaid dollars.

And much of their workforce, including nursing assistants, receive low pay and often are without health insurance or sick leave. Those employees may have elected to stay at home during the pandemic over fears of contracting COVID-19, or leave entirely, enticed by higher paying jobs in other industries like retail or food service, Frogner said.

Anything that exacerbates staff turnover at nursing homes is a problem, according to experts. Even before the pandemic, the turnover rate for registered nurses and certified nursing assistants was 141% and 130%, respectively, according to research.

Lack of workers at post-acute sites of care trickles upstream and affects hospital staffing as well.

“I wish that there was a bit of recognition that what is happening in one healthcare setting is really a kind of cascading effect that’s happening across the healthcare system.”

 

Bianca Frogner

University of Washington School of Public Health professor

The inability to take on patients being discharged from hospitals means hospitals have longer patient stays, which burdens hospital staff who now have to take on an increased patient load, Frogner said.

Hospitals have also struggled to hire and retain staff during the COVID-19 pandemic — many were forced to turn to high-cost travel nurses to fill in gaps.

“That is a potential pretty significant relationship to the staffing issues that hospitals are facing” — and one that is likely to continue as workers have attractive job options outside of healthcare and without significant investments or changes in how nursing home pay is structured, Frogner said. “I wish that there was a bit of recognition that what is happening in one healthcare setting is really a kind of cascading effect that’s happening across the healthcare system, and that many places are really interconnected more than people realize.”

Delayed care, authorization holdups and more

Other factors are also contributing to elongated patient lengths of stay.

During COVID-19, one in three adults put off non-emergent care, worsening health conditions and giving rise to complications. Many patients now need higher acuity care, experts said.

The Mayo Clinic in August said it was operating “at near capacity” due to its increase in patient days, which were up 7.6% from 2021 in the first six months of the year. The academic medical center chalked it up to capacity constraints as well as a “changing mix” of hospital patients needing to stay longer.

Sicker patients staying longer tend to require more costly resources, like specialty pharmaceuticals. And the cost of those resources has increased due to supply chain issues, rising drug costs and inflation, which exacerbates the issue, according to Healthcare Financial Management’s Gundling. Hospitals are spending 6% more on supplies and 5% more on drugs than in 2020.

In addition, many older patients have moved to Medicare Advantage plans, which currently cover almost half of the entire Medicare population. It can take a few days for hospitals to hear back from plan administrators on whether they’re authorized to discharge patients to other post-acute services. That extends days spent in the hospital, said Kaufman Hall length-of-stay expert Brian Pisarsky.

The roughly three-fourths of patients who are discharged home also face bottlenecks. Hospitals are facing shortages of durable medical equipment, like oxygen tanks or walkers, that patients may need in order to manage their followup care at home, Pisarsky said.

As a result, facilities have to wait to discharge until they receive the needed durable medical equipment.

How hospitals can help

Overall, experts don’t expect larger headwinds to ease up, absent significant investments in the healthcare workforce — but that doesn’t mean hospitals are entirely devoid of interventions to ensure they’re able to staff crowded beds.

Beyond offering higher wages to attract workers to manage patients who are staying longer, hospitals could propose benefits such as paying for school tuition, paid sick leave, subsidized transportation and more training opportunities, according to Frogner.

Hospitals might balk at spending extra money on these benefits, but are likely to save money down the line by keeping workers on board, Frogner added.

“You can turn on the TV and watch a commercial from Amazon that advertises all these additional benefits, other than pay, that they offer their workers. I don’t know the last time I’ve seen — or if I’ve ever seen — a hospital or a nursing home advertise those same things,” Frogner said.

In addition, hospitals should begin discharge planning earlier, so that when a patient is ready to leave the facility a plan is already in place, Pisarsky said.

That means referring asks for any post-acute care approvals to insurance companies earlier; taking steps like multidisciplinary rounding or observation huddles multiple times a day to ensure a care team is on the same page about patient needs; shoring up post-acute provider partnerships and just generally being proactive about the day-to-day blocking and tackling of patients, according to Pisarsky.

Hospitals can also take steps like adopting better models of team-based care, streamlining efficiencies around health IT usage to cut down on click fatigue, automating route tasks with artificial intelligence or robotics and revisiting CEO compensation to free up more dollars. All options should be on the table to ease the growing bottleneck of patients, freeing up staff and dollars to provide better patient care, experts said.

Otherwise, “this ripple effect can really tear through a hospital quickly and jam everything up,” warned Kaufman Hall’s Swanson

https://www.healthcaredive.com/news/hospitals-length-stay-nursing-home-labor-discharge/630871/

Takeda to stop making parathyroid drug Natpara in 2024 after production challenges

 Takeda will stop manufacturing its medication Natpara for a rare endocrine condition at the end of 2024 after failing to resolve longstanding production issues.

The Japanese drugmaker has struggled with persistent supply challenges posed by the unique manufacturing process for the drug, a bioengineered replica of human parathyroid hormone. Takeda has also been unable to find a way to prevent contamination of rubber particles from the drug’s injector cartridge.

For years it has explored solutions for both issues, but “despite these efforts, Takeda has unfortunately determined there is not a sustainable or viable path forward,” the company said Tuesday.

Natpara treats low levels of parathyroid hormone in patients with hypoparathyroidism, a rare condition that leads to low blood calcium levels and related health problems in an estimated 70,000 people in the U.S.

For patients who cannot control their blood calcium levels with calcium and Vitamin D supplements, the loss of the drug leaves them without alternate medications. In addition, patients who abruptly stop taking Natpara can suffer from serious complications such as severe pain, kidney damage and cardiac events.

The announcement comes after three years of setbacks with the drug since Takeda acquired it via its $62 billion takeover of Shire in 2019.

In September 2019, the rubber contamination issue led Takeda to issue a U.S. recall, pulling the drug from the market. Patients taking the drug maintained access to it through a Food and Drug Administration special use program. The company in early 2021 said it would take another year for the drug to return to the U.S. market, but a year later the FDA rejected its application.

The FDA approved Natpara in 2015, weeks after its manufacturer NPS Pharma agreed to be bought by Shire.

Now, Takeda said its priority is to maintain supply for patients taking the drug in the U.S, Europe (where it is sold as Natpar) and other regions, and after 2024, until inventory is depleted or expired. The company said it “has great empathy for hypoparathyroidism patients who rely on Natpar/Natpara and deeply regrets that we could not resolve these issues.”

There are around 420 patients enrolled in the U.S. special use program, a Takeda spokesperson told BioPharma Dive.

“After consultation and alignment with regulatory authorities, we have communicated this update to patients’ prescribers and are reaching out directly to all patients enrolled in the U.S. Special Use Program to allow for these patients to consult with their healthcare teams to develop longer-term treatment plans,” the company said in an emailed statement.

https://www.biopharmadive.com/news/takeda-stop-production-natpara-hypoparathyroidism/633295/