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Monday, April 8, 2024

Eclipse could cut US solar output by 40 GWh--how 5 grid operators are preparing

 A total eclipse on Monday will mean the loss of thousands of megawatt-hours of solar generation across portions of the United States — likely impacting more generation than in any previous solar eclipse, experts say.

Grid operators across the nation have been preparing for months and say they can navigate the event with no impact to reliability. But they also say their efforts are complicated by uncertain weather outlooks, and eclipse-related behavioral changes that make forecasting energy demand difficult.

While the “path of totality” will pass over just a portion of the solar facilities in the U.S., and cloud cover will impact the extent of lost production, “the effects of this eclipse will be significant on solar generation across the country,” said Solcast lead data scientist Hugh Cutcher. The company offers solar irradiance data and forecasting technology.

Solcast estimates that across all U.S. grids, maximum generation losses over the span of the eclipse could be up to 39.9 GWh, with about 16.2 GWh of the loss from rooftop solar. 

US solar plants in the path of totality for the April 8 eclipse

Grid operators including ERCOT, PJM and the New York ISO are planning for losses in solar production during the eclipse, but say that the total amount of lost generation will largely depend on the weather that day.

Despite the reduced renewables, “at the end of the day, we’re going to be fine,” said Michael Lee, CEO of Octopus Energy US, a demand response provider operating in the Texas market.

Experts broadly expect natural gas to take up most of the solar slack during the eclipse.

“We anticipate gas being the most likely solution, as the eclipse is very predictable, and every grid has the gas infrastructure to meet this demand event, which will be more than last year, both due to the path of the eclipse and increases in capacity since October,” Harry Woods, Solcast head of marketing, said in an email.

Flexible loads and batteries will also play a role, said Lee. “Demand response and flexibility can create a low-cost grid,” he said. But ultimately, “this event is only for an hour, and managing millions of thermostats while people are typically going to be outside looking at the eclipse is low-hanging fruit.”

California has long been known as a leader in solar generation but will see relatively mild impacts — perhaps losing 5%-6% of typical daily solar generation — due to the path of the eclipse, according to Solcast. PJM Interconnection and the Electric Reliability Council of Texas markets could see losses up to 10%-11% of daily solar generation.

But forecasts of solar generation losses aside, how are grids in different regions of the U.S. planning for the upcoming event?

California ISO

California is no stranger to high penetration solar or eclipses: In October, it experienced an annular eclipse which impacted the grid from about 8:40 a.m. to 9:30 a.m. During that event, grid scale solar production dropped off at a rate of about 82 MW/minute, ultimately reducing output by about 9,600 MW, relative to production on a typical clear sky day, according to California Independent System Operator officials.

Monday’s eclipse will have less of an impact than the 2023 event, but it is somewhat complicated by the state’s rapid solar buildout. During the October 2023 eclipse, there was more than 16,500 MW of grid-scale solar capacity installed throughout CAISO, according to the grid operator. Now there is more than 18,500 MW. 

“Even though it’s only been a little over six months [since the 2023 eclipse], we’ve had quite a bit of growth in both grid-scale and behind-the-meter solar” across CAISO and the Energy Imbalance Market it manages, ISO Senior Energy Meteorologist Jessica Stewart said during a March planning meeting.

In the upcoming event, Stewart said the state will experience eclipse impacts from about 10 a.m. to 12:30 p.m., with grid-scale solar capacity dropping about 79 MW per minute until maximum solar obfuscation. On the return, solar will ramp up at a rate of about 84 MW per minute, increasing about 6,700 MW to full production.

Pricing impacts of the solar eclipse will not be known until day-ahead and real-time price formation occurs, officials said.

ERCOT

The grid operator for most of Texas said it expects solar generation to be impacted for a three-hour period, with greatest impact at 1:40 p.m., reducing solar generation to about 7.6% of its maximum clear sky output.

ERCOT has asked all market participants to “monitor the operating conditions for this day and make adjustments to current operating plans as needed,” but expects normal operations during the event.

The grid operator is “working with solar forecast vendors to ensure the forecasting models account for the impact of the eclipse,” according to a planning presentation given to the grid operator’s Reliability and Operations Subcommittee last month. “ERCOT will pre-posture the system as necessary to meet both the down and up solar ramps and use ancillary services for additional balancing needs.”

That will likely include the new ERCOT contingency reserve service, said Lee, which will keep thermal and battery assets on standby. But the “primary tool” to meeting changing demand during the eclipse “is still the energy price.”

“As we see supply changing, real-time energy prices will fluctuate,” he said. “And that fluctuation is great because it inspires more generation to come online, and it also inspires load flexibility to start participating.”

PJM Interconnection

Just how much solar generation is lost “will depend on the weather pattern that day,” according to Michael Stewart, PJM senior engineer, load forecasting. He outlined preparations at a March 7 Operating Committee meeting.

The grid operator is preparing for the loss of 80%-85% of production from 8,200 MW of grid-connected resources. There are also about 4,800 MW of behind-the-meter resources that will be impacted, increasing demand on the grid.

There are several variables that could impact load, including school closures or eclipse-related travel, Stewart’s presentation noted. This is “not a holiday, but not a normal Monday.”

“With a close eye on weather forecasts, PJM is preparing to dispatch generation as needed to respond to solar power losses, including reserve and regulation resources as required,” the grid operator said in a blog post. “Reserve resources can provide needed backup generation when called upon, while regulation resources can provide energy to help control voltage and frequency on the system.”

New York

In 2017, the New York Independent System Operator lost about 500 MW of output during an eclipse that obscured the sun by about 75%.

“Today, we have five times as much solar generation throughout the state, but the amount of cloud cover will ultimately determine how much generation is lost during the eclipse,” Mark Taylor, a technical specialist and meteorologist at NYISO, said in a statement.

If skies are clear on April 8, the grid operator said it expects solar energy production to be about 3,500 MW as the eclipse begins. Production will then drop precipitously across a little more than an hour, likely to about 300 MW, before rising back again to 2,000 MW. The sun will be completely obscured for up to 3.5 minutes at varying parts of the state between 3:15 p.m. and 3:30 p.m.

The ISO’s solar forecasting tools “anticipate how much solar energy production the system can expect throughout the day, and helps our planners and operators determine resource needs to meet expected demand,” the operator said in a blog post. “If unexpected circumstances arise and solar resources aren’t producing power as initially forecasted, the NYISO’s operations team must find a way to make up the difference.”

Midcontinent ISO

The last time an eclipse’s path crossed the Midcontinent Independent System Operator footprint was in 2017, when the grid operator had just 100 MW of solar on its system. Today there is more than 5,000 MW.

“We don’t expect any reliability-related issues,” MISO said in an April 2 blog post.

The eclipse path crosses MISO’s South and Central regions, and two control centers are located in the path of totality. The grid operator anticipates “shifts in darkness” occurring from 1:30 to 4:25 p.m. On a sunny day, the grid operator said it could see an estimated 4 GW drop in generation over the course of 90 minutes, followed by a 3 GW rebound.

While forecasting electricity demand for a typical day “is typically straightforward,” MISO noted that Monday “will not be a typical spring day.”

School closures, changed business hours, busier hotels and restaurants, and potentially cooler temperatures because of the darkness “make it more challenging to accurately forecast electricity demand for the day,” the grid operator said.

https://www.utilitydive.com/news/grid-operators-april-8-total-solar-eclipse/712099/

Labcorp to Expand Precision Oncology Portfolio

 LabCorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services, announced today the strategic expansion of its precision oncology portfolio, solidifying its commitment to advancing cancer research and patient care on a global scale. The announcement underscores Labcorp's dedication to investing in scientific, diagnostic and laboratory innovations to support its pharmaceutical, biotechnology and clinical research partners in bringing groundbreaking therapies to market.

https://www.biospace.com/article/releases/labcorp-announces-expansion-of-precision-oncology-portfolio-to-support-pharmaceutical-biopharma-and-clinical-research-in-advancing-drug-development-programs/

AstraZeneca, Daiichi Sankyo Win First Tumor-Agnostic HER2 FDA Approval for Enhertu

 The FDA on Friday approved AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu (fam-trastuzumab deruxtecan-nxki) for the treatment of HER2-positive solid tumors in adults who have undergone prior systemic treatment and have no alternative treatment options.

With Friday’s approval, Enhertu becomes the first tumor-agnostic HER2-directed therapy authorized for administration, and the first antibody-drug conjugate (ADC) to win such an indication, according to the companies.

The approval was granted under the FDA’s accelerated pathway using objective response rate (ORR) and duration of response (DoR) data. To keep Enhertu’s tumor-agnostic indication, AstraZeneca and Daiichi Sankyo will need to run a Phase III confirmatory trial to verify its clinical benefit.

Daiichi Sankyo CEO Ken Keller in a statement called the regulatory win a “significant milestone” for eligible patients across a broad range of tumor types, for whom Enhertu is now available as a treatment option.

“The accelerated approval by the FDA for this tumor-agnostic indication is based on the clinically meaningful efficacy seen with Enhertu across numerous types of metastatic cancers,” Keller added.

Data from the Phase II DESTINY-PanTumor02 trial, which enrolled nearly 470 patients with HER2-positve solid tumors, showed that Enhertu had an ORR of 37.1% after a median follow-up of 12.75 months, while its overall DOR was 11.3 months. The study recruited patients with a variety of tumor types, including biliary tract cancer, bladder cancer, cervical cancer, pancreatic cancer and certain rare tumors.

The results, which were published in October 2023 in the Journal of Clinical Oncology, demonstrated that the ADC also resulted in 6.9 months of median progression-free survival and 13.4 months of median overall survival.

Results from the DESTINY-Lung01 and DESTINY-CRC02 Phase II studies also supported Friday’s approval, which together showed that Enhertu has strong antitumor activity against metastatic non-small cell lung cancer and colorectal cancer.

Enhertu is an ADC that works by seeking out and binding to the HER2 protein, which is typically found on several solid tumors. Enhertu’s toxic payload is the small molecule DXd, a topoisomerase I inhibitor that is released inside the cancer cell and damages the DNA, triggering cell death.

The FDA first approved Enhertu in December 2019 for the treatment of HER2-positive unresectable or metastatic breast cancer in patients after two or more anti-HER2 therapies. Enhertu has since picked up several indications including for gastric cancer and non-small cell lung cancer.

The ADC carries a boxed warning for interstitial lung disease and embryo-fetal toxicity. Patients on Enhertu should be under tight monitoring for signs such as cough, dyspnea, fever and other respiratory symptoms.

https://www.biospace.com/article/astrazeneca-daiichi-sankyo-win-first-tumor-agnostic-her2-fda-approval-for-enhertu/

5 Successful Phase III Oncology Trials in Q1

 In the oncology space, drug developers are keen to develop cutting-edge solutions—and lay claim to a piece of a market estimated to hit $359.1 billion by 2028. However, most Phase III trials fail to present significant clinical improvements on the standard of care. 

"Oncology . . . is huge because there are some successes, but there’s still a huge medical need,” Ansbert Gadicke, managing partner at MPM BioImpact, told BioSpace earlier this year. 

Vlad Vitoc, CEO of the immune-oncology company MAIA Biotechnology, concurred. “These trials are important for the niche patient populations they serve,” he told BioSpace. Vitoc lauded successful recent Phase III trial successes as welcome advancements, noting that they will improve care options for patients beyond what is currently available. 

Here, we highlight five such trials with game-changing potential for oncology and the potential to influence the current market. 

1. BMS Well-Positioned to Compete in First-Line Liver Cancer Market

Bristol Myers Squibb is knocking on the door of a liver cancer market currently led by AstraZeneca and Roche. In March, BMS revealed that Opdivo and Yervoy improved survival in patients with untreated advanced hepatocellular carcinoma (HCC) in the Phase III CheckMate-9DW trial compared to the investigator’s choice of therapy sorafenib or lenvatinib.

The Checkmate-9DW trial comprised 700 people with untreated advanced HCC given BMS’s combo or sorafenib or lenvatinib. The study hit its primary overall endpoint, with interim analysis showing that patients in the Opdivo and Yervoy arm were living longer than those in the control arm.

An FDA approval of the Opdivo/Yervoy combo would position BMS to compete in the first-line liver cancer market alongside Roche and AstraZeneca. Roche's checkpoint inhibitor Tecentriq was approved by the FDA in combination with VEGF inhibitor Avastin in 2020. Two years later, AstraZeneca won approval for Imjudo combined with Imfinzi.  

2. Pfizer Seeks Eighth Indication for ADC Adcetris

Also last month, Pfizer recorded positive results from a Phase III trial for its Adcetris regimen in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). Adcetris—an antibody-drug conjugate (ADC) known as brentuximab vedotin—combined with lenalidomide and rituximab showed “statistically significant and clinically meaningful” improvements in overall survival, the trial’s primary endpoint, compared to lenalidomide and rituximab plus placebo. Adcetris also showed significant improvement in the secondary endpoints of progression-free survival (PFS) and overall response rate (ORR).

While full data from the ECHELON-3 trial have not yet been shared, Pfizer said Adcetris’s safety and tolerability were consistent with previous findings recorded with the drug when used to treat patients with refractory or relapsed DLBCL. With these data in hand, Pfizer will engage with the FDA regarding a regulatory submission, according to the press release. An approval would mark the eighth indication for Adcetris, which was initially approved in 2011.

3. Asieris Data Spark Hope for Non-Surgical HSIL Treatment

There could soon be a non-surgical option for cervical high-grade squamous intraepithelial lesions (HSIL). On March 18, Chinese biopharma Asieris Pharmaceuticals reported that treatment with its cold light photodynamic drug-device combination APL-1702 demonstrated significant efficacy in a Phase III trial, with advancements in high-risk HPV16 and HPV18 clearance rates.

Patients treated with APL-1702 showed a statistically significant improvement of 89.4% compared to the placebo control group, Asieris stated in its announcement. The product had a “good” safety profile, according to the company. The trial included 402 eligible patients from across China, Germany and the Netherlands, among other countries.

Cervical cancer is the fourth most common cancer in women. Its primary cause is human papillomavirus infection, which causes cervical lesions. Experts project that by 2030, around 16 million people will have HSIL worldwide. 

4. Novocure Clocks Positive Data in Brain Metastases from NSCLC

An innovative treatment is showing promise in treating brain metastases from NSCLC. Last month, Swiss biotech Novocure reported its Tumor Treating Fields (TTFields) therapy met the primary endpoint in the Phase III METIS clinical trial, demonstrating a statistically significant improvement in time to intracranial progression when combined with supportive care compared to supportive care alone. TTFields uses electric fields that act via many different mechanisms to kill cancer cells.

The trial consisted of 298 adult patients with up to 10 brain metastases from NSCLC following stereotactic radiosurgery who received either TTFields or supportive care, including treatments with steroids, anti-coagulants, anti-epileptic drugs, pain control and nausea control. If a second intracranial progression was confirmed, patients were allowed to cross over to the experimental arm. 

Treatment with the therapy was well-tolerated, with sustained quality of life and neurocognitive functions, according to Novocure.

TTFields was first approved by the FDA in 2011 for the treatment of recurrent glioblastoma and Novocure CMO Nicolas Leupin said the company continues to explore the capabilities of this therapy in a variety of solid tumor types. “At Novocure, we pursue aggressive, difficult to treat cancers because we are passionate about helping patients and we believe in the science of TTFields therapy,” Leupin told Biospace

5. Roche Reports Phase III TIGIT Win

Finally, in January, Roche subsidiary Genentech posted positive Phase III data for its anti-TIGIT immunotherapy tiragolumab when used in combination with Tecentriq and chemotherapy. The SKYSCRAPER-08 study, one of seven Phase III trials ongoing for tiragolumab, enrolled 461 patients with esophageal squamous cell carcinoma (ESCC) from Asian countries randomized into a treatment arm and control arm. Tiragolumab combined with Tecentriq and chemotherapy improved PFS compared to chemo alone. 

The anti-TIGIT market has been a challenging one to crack, with other key players failing to meet their targets. Novartis ended its partnership with BeiGene for an anti-TIGIT therapy in non-small cell lung cancer (NSCLC) last year, taking a $300 million loss. Merck’s Keytruda plus anti-TIGIT vibostolimab also failed to meet the primary endpoints in a Phase II NSCLC study in 2023.

Gilead and Arcus Biosciences have fared better, recording “encouraging results” in a Phase II trial for Giliead’s domvanalimab, an anti-TIGIT antibody, used in combination with Arcus’s anti-PD-1asset zimberelimab and chemo, according to the partners’ November 2023 announcement.

Further growth in the anti-TIGIT market is anticipated, with more than 40 anti-TIGIT antibodies in clinical trials around the world.

https://www.biospace.com/article/5-successful-phase-iii-oncology-trials-in-q1-/

ACC24 Roundup: Novo, Ionis Tout Cardio Victories and Boehringer, Lilly Disappoint

 The American College of Cardiology’s 73rd Annual Scientific Session & Expo (ACC24) took place over the weekend in Atlanta, spotlighting the latest and most impactful innovations in the field of cardiovascular care.

BioSpace has highlighted below some of the most notable presentations from ACC’s Annual Scientific Session.

Novo Builds Wegovy’s Cardio Case, Eyes Heart Failure

Still riding high from winning its recent cardiovascular approval for Wegovy (semaglutide), Novo Nordisk is continuing its expansion into heart health with new promising data from its Phase III STEP-HFpEF study.

At 52 weeks, patients treated with the blockbuster obesity drug saw a significantly greater reduction in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) versus placebo. Wegovy also outperformed the placebo group in terms of body weight reduction, six-minute walk distance and C-reactive protein levels.

Taken together, these findings suggest that Wegovy could significantly ease symptomatic burden and physical limitations in patients with obesity, heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus. The GLP-1 treatment also boosted patients’ exercise function and weight loss.

Results from the large Phase III trial, which randomized more than 600 patients, were also published on Friday in The New England Journal of Medicine.

Novo previously posted heart failure findings for Wegovy, announcing in August 2023 that the weight-loss medication could significantly improve KCCQ-CSS scores in the Phase III STEP trial, which enrolled patients with obesity and HFpEF, but not diabetes.

Novo has submitted data from these two studies to the FDA, seeking to expand Wegovy’s label to include HFpEF, STAT News reported.

Ionis Moves Toward Rare Metabolic Disorder Approval

Ionis Pharmaceuticals unveiled promising results from its Phase III BALANCE study at ACC24, showing that its investigational RNA-targeted antisense therapy olezarsen can reduce triglyceride levels in patients with familial chylomicronemia syndrome (FCS).

At six months, patients treated with the 80-mg dose of olezarsen saw a 44% placebo-adjusted reduction in triglyceride levels, an effect that was statistically significant, with a p-value less than 0.001, according to Ionis. This effect continued and improved through 12 months, reaching a 59% placebo-adjusted reduction.

Patients in the olezarsen arm also developed “markedly fewer” acute pancreatitis events over 12 months of follow-up.

CEO Brett Monia in a statement said that these results from BALANCE support “the potential for olezarsen to be the standard of care for patients with FCS, if approved,” adding that the company is “working closely with the FDA” for olezarsen’s regulatory application, which Ionis expects to file later this year.

Ionis in September 2023 revealed early data from BALANCE. At the time, olezarsen elicited a 100% reduction in acute pancreatitis events versus placebo.

Olezarsen is an RNA-targeted ligand-conjugated antisense treatment that works by lowering the body’s production of the apoC-III protein, which is produced in the liver and is involved in the regulation of triglycerides in the blood. Aside from FCS, Ionis is also studying the candidate in severe hypertriglyceridemia.

Boehringer, Lilly’s Jardiance Misses in Myocardial Infarction

Data from Boehringer Ingelheim and Eli Lilly’s Phase III EMPACT-MI trial showed that their SGLT2 inhibitor Jardiance (empagliflozin) does not significantly reduce the risk of heart failure hospitalization or death from any cause in patients who had suffered an acute myocardial infarction (MI) episode.

At a median follow-up of 17.9 months, 267 patients in the Jardiance arm developed the composite primary endpoint of being hospitalized for heart failure or dying from any cause. This figure corresponds to a rate of 8.2%, whereas the primary outcome arose in 9.1% of those patients in the placebo arm.

The between-group difference did not reach statistical significance, with a p-value of 0.21, according to the ACC’s news release on the results.

However, disaggregating the primary endpoint into its components showed that Jardiance could significantly lower the risk of a first hospitalization for heart failure by around 23% versus placebo.

EMPACT-MI lead author Javed Butler in a statement said that Jardiance “did not reduce mortality after a heart attack, but did reduce the risk of heart failure after heart attack,” adding that this “25% to 30% reduction” in heart failure hospitalizations is “pretty clinically meaningful.”

Jardiance also failed to elicit significant improvements in EMPACT-MI’s key secondary endpoints. An exploratory analysis also found no benefit on cardiovascular death, time to death from cardiovascular causes, as well as time to first heart failure hospitalization or cardiovascular death.

Arrowhead Shoots for Pivotal SHTG Study for Candidate

Arrowhead Pharmaceuticals unveiled Phase IIb data for its investigational RNAi therapy plozasiran at ACC24, demonstrating steep triglyceride reductions at 24 weeks in patients with severely elevated triglyceride levels who are at risk of developing acute pancreatitis.

In the mid-stage SHASTA-2 trial, Arrowhead’s asset reduced triglyceride levels by 74% while placebo only elicited a 17% decrease. Plozasiran also met the study’s key secondary endpoint, with its highest doses triggering a 58% average drop in triglyceride at 48 weeks versus 7% in the placebo group.

ApoC3, a liver protein that disrupts the clearance of fats from the body, was lowered by 48% among plozasiran-treated patient at 48 weeks. Placebo comparators, meanwhile, saw a 4% increase in ApoC3 at this time point.

SHASTA-2 lead author Daniel Gaudet said in a statement that these findings “support the initiation of pivotal studies of plozasiran for the treatment of severe hypertriglyceridemia.”

Plozasiran is an investigational RNAi therapeutic that works by interrupting the expression of the ApoC3 gene, resulting in overall lower levels of the protein. This mechanism of action could block the pathologic function of ApoC3 and help normalize lipid levels in patients, according to Arrowhead’s website.

https://www.biospace.com/article/acc24-roundup-novo-ionis-tout-cardio-victories-and-boehringer-lilly-disappoint/