PRX-115 promising treatment option for patients with gout, finds study

A recent study presented by Orit Cohen Barak in the ACR Convergence 2024 showed that with the extra advantage of a potentially broad dose interval, PRX-115 (Protalix BioTherapeutics) may provide an efficient urate-lowering medication that might improve patient compliance and treatment flexibility of gout cases.

PEGylated uricases have previously shown promise as a therapeutic approach for treating individuals with refractory gout. Utilizing a novel plant cell-based expression technique, the recombinant homotetrameric uricase enzyme PRX-115 is generated from Candida utilis. After purification, the enzyme undergoes a unique modification using unique polyethylene glycol (PEG) molecules. High specific activity, enhanced stability, and decreased immunogenic potential are all features of PRX-115’s design.

A single intravenous (IV) infusion of PRX-115 was used to evaluate its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in a first-in-human single ascending dosage, double-blinded research (FIH-SAD, NCT05745727). A total of 64 participants, the majority of whom had high urate levels (>6.0 mg/dL), were recruited for the trial and randomly assigned to either PRX-115 or a placebo in a 3:1 ratio (8 cohorts; 6 participants on active and 2 on placebo each cohort). The participants were monitored for 12 weeks, or 85 days. 

The findings suggest that PRX-115 single ascending dosages were usually well tolerated, according to key findings from the first 7 cohorts. A total of 18 associated Treatment Emergent Adverse Events (TEAEs) were reported by 11 (26%) subjects who received PRX-115; most of them were mild to moderate and temporary in character. At a modest dosage, one significant adverse event (SAE, anaphylactic response) happened right after the infusion started. The person persisted in the trial when the SAE had completely resolved.

Exposure to PRX-115 grew in a dose-dependent manner, with detectable amounts up to 85 days (12 weeks) after treatment at the high dosages and peak concentrations being recorded right after infusion. A single dosage of PRX-115 quickly lowered plasma urate below 6.0 mg/dL in all tested doses. With urate levels below 6.0 mg/dL that persisted for 12 weeks, the urate-lowering efficacy and response duration were dose-dependent.

Overall, the findings of this FIH-SAD study’s first seven cohorts show that PRX-115 may be able to provide a broad dose interval and is a potentially effective therapy choice for gout patients. To validate these results and determine PRX-115’s long-term safety and effectiveness in gout patients, more research is necessary.

Source:

Prolonged plasma urate-lowering after a single intravenous administration of PRX-115, a novel PEGylated uricase, in participants with elevated urate levels. (2024, October 15). ACR Meeting Abstracts. https://acrabstracts.org/abstract/prolonged-plasma-urate-lowering-after-a-single-intravenous-administration-of-prx-115-a-novel-pegylated-uricase-in-participants-with-elevated-urate-levels/

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PET CT outperforms Computed Tomography Scan in determining suspected Bone metastasis: Study

A recent study found that fluorodeoxyglucose
positron emission tomography/computed tomography ([18F] FDG
PET/CT) was better for determining bone biopsy sites and identifying bone
metastasis. It was also more cost-effective than computed tomography, as per the
trial results published in the Cancer Imaging journal

More than half of all cancers
develop metastasis, and bone is the most common site of metastasis after the
lungs and liver. This metastasis often leads to the development of complicated
skeletal-related events like fractures, spinal cord compression, etc, affecting
the quality of life and survival rates. Hence, early diagnosis is essential in
cancers. Bone biopsy of the suspected tissue is the gold standard test. Imaging
techniques like scintigraphy, computed tomography scans, and [18F] FDG
PET/CT are essential for guiding bone biopsies. Even though [18F] FDG
PET/CT offers high accuracy, its accessibility is limited in certain areas. Hence,
researchers conducted a study to determine whether [18F] FDG PET/CT
could more accurately determine a puncture site than CT to improve the
diagnostic accuracy of biopsy. They also determined the best cutoff value of
clinical indicators for differentiating malignant bone metastases using a
noninvasive examination and [18F] FDG PET/CT.

Also Read: Bone Mineral Density Declines More Rapidly in Adults With Cystic Fibrosis, finds study

A prospective, single-center,
comparative imaging study compared the performance of [18F] FDG
PET/CT with CT in detecting bone metastases. Between 2020 and 2021, about 273
patients with bone lesions were enrolled and treated. Patients were randomly
assigned to undergo the scans before biopsy to determine the puncture site. The
two imaging tests’ accuracy, sensitivity, specificity, second biopsy rate,
diagnostic time, and cost-effectiveness were compared.

Findings:

  • The [18F] FDG PET/CT group showed a
    significantly higher accuracy and sensitivity in detecting bone metastases than
    the CT group.
  • The need for a second biopsy was also significantly
    lower in the [18F] FDG PET/CT group.
  • The [18F] FDG PET/CT group showed a
    lesser diagnostic time of 18.33 ± 2.08 days than 21.28 ± 1.25 days in the CT
    group ( P < 0.05).
  • The cost of [18F] FDG PETCT is
    11428.35 yuan, and the cost of CT is 13287.52 yuan; the incremental cost is
    1859.17 yuan.
  • SUVmax > 6.3 combined with ALP > 103 U/L demonstrated
    a strong association for tumor metastases with an AUC of 0.901.
Also Read: False-Positive Mammograms May Deter Women from Future Screenings: Research Finds

Thus, the researchers concluded
that [18F] FDG PET/CT is better suited and cost-effective than CT for
localizing the bone biopsy site for suspect bone metastases. The authors also
recommended [18F] FDG PET/CT as an imaging test for localizing the site of bone
biopsy.

Further reading: Chang, Y., Gu,
Y., Ruan, S. et al. [18F]FDG PET/CT performs better
than CT in determining the bone biopsy site : randomized controlled clinical
trial. Cancer Imaging 24, 160 (2024). https://doi.org/10.1186/s40644-024-00804-6.

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AstraZeneca Estimates Rs 35 Crore Tax Benefit After ITAT Remands Transfer Pricing Issues

New Delhi: AstraZeneca Pharma India Limited has estimated a potential tax benefit of approximately Rs 35 crore following a favorable ruling from the Income Tax Appellate Tribunal (ITAT) on its tax disputes for the assessment years 2017-18 and 2018-19. The ITAT granted full relief on corporate tax matters, while remitting the transfer pricing issues back to the Assessing Officer (AO) for further review, in line with its directions.

The company disclosed the development to the stock exchanges, indicating that the final tax impact will be determined once the AO completes the review process.

The ITAT’s decision granted complete relief to the company on corporate tax matters. However, the tribunal remitted the transfer pricing issue back to the Assessing Officer for further review, directing that the matter be resolved in line with the ITAT’s guidance.

In a ruling on November 26, 2024, the ITAT, Bangalore delivered its judgment concerning the appeals filed by AstraZeneca Pharma India Limited against the assessment orders for the assessment years 2017-18 and 2018-19.

The company had contested various adjustments made by the Assistant Commissioner of Income Tax (ACIT), Bengaluru, related to transfer pricing and other corporate tax matters.

Key Issues and Rulings

  1. Transfer Pricing Adjustments: One of the primary issues in the appeals related to adjustments made in transfer pricing, specifically concerning the Unilateral Advance Pricing Agreement (APA) entered between the company and the Central Board of Direct Taxes (CBDT) in June 2023. This agreement covered assessments for the years 2016-17 to 2020-21. AstraZeneca’s arguments were accepted, as the adjustments were found to be resolved through the APA, rendering the adjustments for these years unnecessary. As a result, these grounds were dismissed by the Tribunal.
  2. Selling, Marketing, and Distribution Expenses: A major point of contention was the disallowance of Rs. 30,47,64,640 for selling, marketing, and distribution expenses. The Tribunal noted that this issue had been previously raised in the assessment year 2016-17, and the matter had been remitted to the Assessing Officer (AO) for fresh adjudication. The Tribunal decided that this issue should also be sent back to the AO/TPO for proper review, aligning with the directions from the earlier ruling.
  3. Club and Entrance Fees: Another significant matter concerned the addition of Rs. 1,78,659 for club and entrance fees, which the Assessing Officer (AO) had disallowed as personal expenditure. The Tribunal observed that the Dispute Resolution Panel (DRP) had already ruled in favor of AstraZeneca, directing the AO to delete this addition. However, the AO had failed to comply, and the Tribunal ordered that the addition be deleted in accordance with the DRP’s direction.
  4. Adjustment of Book Profits under Section 115JB: A contentious issue revolved around the adjustment of book profits under Section 115JB of the Income Tax Act, particularly regarding transfer pricing adjustments. The AO had added adjustments related to transfer pricing and other corporate disallowances to the book profits. However, the Tribunal ruled that such adjustments were not permissible under Section 115JB, referencing previous rulings that disallowed such adjustments. The Tribunal thus directed the AO to exclude these adjustments in the final computation of book profits.
  5. Penalty Proceedings: The Tribunal also addressed the initiation of penalty proceedings under Section 270A, but determined that it was premature to make any decision at this stage, dismissing the issue as infructuous.

The Tribunal’s final decision was favorable to the appellant, AstraZeneca Pharma, in several areas, especially regarding the corporate tax issues and the treatment of certain expenses.

The case will now be returned to the Assessing Officer for further proceedings, particularly on the transfer pricing adjustments and other disallowed expenses. The final ruling also confirmed the company’s favorable tax impact of approximately Rs 35.01 crores, though this remains an estimate pending the completion of the AO’s review.

The Tribunal’s order on the two appeals, IT(TP)A Nos. 419 & 876/Bang/2022, covering both the assessment years 2017-18 and 2018-19, is partially allowed, mainly for statistical purposes, as the matters are to be further adjudicated by the AO in line with the Tribunal’s directions.

Meanwhile, in its recent communication to the stock exchanges, AstraZeneca disclosed about the ITAT order, adding that the company will now work with the AO to ensure that the final order aligns with the ITAT’s directions.

Further, expressing on the financial implications, the drug maker said, “The expected overall financial implication cannot be determined at this stage. However, the estimated favorable tax impact on account of the captioned ITAT order could be Rs. 35.01 crores (approx.).”

To view the original order, click on the link below:

https://indiankanoon.org/doc/85401656/

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Broken sleep a hallmark sign of living with the most common liver disease, scientists find

The prevalence of MASLD (metabolic dysfunction-associated steatotic liver disease) is exploding in most regions of the world, boosted by increased obesity and sedentary lifestyles. MASLD (formerly known as non-alcoholic fatty liver disease) is already the most common liver disorder: it affects 30% of adults and between 7% and 14% of children and adolescents, and this prevalence is predicted to rise to more than 55% of adults by 2040.

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Gender inequities may distort estimates of anterior cruciate ligament injury rates among women, study suggests

A study by the Harvard GenderSci Lab in the British Journal of Sports Medicine reveals systematic biases in a key metric used in estimates of sex disparities in anterior cruciate ligament ( ACL) injury rates in sports.

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Health and financial toll of mosquito-borne chikungunya infection likely vastly underestimated, data suggest

The health and financial implications of the emerging threat of mosquito-borne chikungunya viral infection have most likely been significantly underestimated, with total costs probably approaching US$ 50 billion in 2011–20 alone, suggests a comprehensive data analysis, published in the open access journal BMJ Global Health.

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Small amounts of incidental vigorous physical exertion may almost halve major cardiovascular events risk in women

Short bursts of incidental vigorous physical exertion, lasting less than a minute each, may almost halve the risk of a major cardiovascular event, such as heart attack or heart failure among women who don’t exercise regularly, finds research published online in the British Journal of Sports Medicine.

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Research reveals upcoding in hospital stays leads to billions in extra payments

In five states over nearly a decade, hospitals have increased how frequently they document patients as needing the highest intensity care, which has led to hospitals receiving billions in extra payments from health plans and government programs, according to a new RAND study.

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Intas Pharma to acquire Udenyca business from Coherus BioSciences

Raleigh: Accord BioPharma, Inc., the U.S. specialty division of Intas Pharmaceuticals, Ltd., focused on the development of oncology, immunology and critical care therapies, has announced that Intas Pharmaceuticals has signed an agreement to acquire the UDENYCA (pegfilgrastim-cbqv) business from Coherus BioSciences, Inc.

UDENYCA is a pegfilgrastim biosimilar to Neulasta and is typically administered the day after chemotherapy to decrease the incidence of infection as caused by febrile neutropenia. During the 2023 fiscal year, sales of UDENYCA totaled $127.1 million. “When final, the acquisition will expand Accord BioPharma’s product portfolio and is expected to position the company for accelerated growth in the biosimilar industry,” the release stated.

UDENYCA is a pegfilgrastim biosimilar approved in the United States currently available in three administration options — prefilled syringe (PFS), autoinjector (AI) and on-body injector (OBI) — providing patients and healthcare providers with choice, control and convenience. Since its launch in 2019, over 300,000 patients have been treated with UDENYCA.

“By adding UDENYCA to our growing portfolio of biosimilars, we will strengthen our business footprint in the U.S.” said Chrys Kokino, U.S. President of Accord. “With an expanding presence in the market, we can fuel the internal innovation and external expansion needed to deliver more accessible treatment options to patients.”

“In considering our strategic pathways to achieve future growth, acquiring the UDENYCA business in the U.S. is appealing for two reasons: the product’s impressive sales and uptake, and its range of administration options that give patients an opportunity to align their needs with a treatment plan,” said Binish Chudgar, Executive Chairman and Managing Director of Intas Pharmaceuticals. “Having an on-body injector within our portfolio will allow us to provide immune supportive care to patients in a variety of settings, including at home, a benefit to patients who live far away from their care center.”

The sale is expected to close in the first quarter of 2025.

UDENYCA is a leukocyte growth factor indicated to:

  • Decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.
  • Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome).

UDENYCA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Read also: Intas Pharmaceutical Gets CDSCO Panel Nod To Manufacture, Market Anti-cancer Drug Pertuzumab

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2nd-year MBBS student commits suicide by jumping from hostel roof

Jaipur: In a tragic incident, an MBBS student committed suicide by jumping from the hostel roof at BR Ambedkar Medical College in Udaipur. The deceased student has been identified as a second-year MBBS student.

According to IANS report, Students informed the police that the medico was studying till 2:30 in the night in his room. Officials said that he jumped around three o’clock from the sixth floor of the hostel.

Speaking to IANS, a police official said that they have taken the body in its custody and kept it in the mortuary of the district hospital.

Also Read: Final year MBBS Medico jumps to death from hostel building in Chennai

Police further informed that the student’s mobile, jacket and slippers were found on the sixth floor.

The police further informed IANS that examinations are going on in the medical college and concerned medico’s paper did not go well two days back. He had also shared about the paper with his friends.

The DSP said that on receiving the information of the incident, he reached the hospital. The body has been kept in the trauma centre.

“Medical college principal Dr Shravan Kumar Meena has given a report. We are awaiting the report of the family members. Further action will be initiated after the report comes,” the DSP said.

Medical Dialogues had earlier reported that final-year medical student of Meenakshi Medical College in Kanchipuram allegedly committed suicide by jumping from the fifth floor of her hostel building. The 23-year-old student, also a trainee doctor at the institute was reportedly suffering from depression due to relationship issues with a fellow medical student. 

According to the police, the student started their relationship in the first year but gradually stopped talking and separated in their third year. This caused her extreme mental and emotional distress.

Also Read: Telangana doctor battling depression jumps to death from 8th floor of apartment

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