Submit safety, efficacy data of Indian Patients: CDSCO Panel Tells AstraZeneca on additional indication of Enhertu 100mg

New Delhi: In response to the drug major AstraZeneca’s proposal for the additional indication of Trastuzumab Deruxtecan Powder Concentrate Solution for Infusion (Enhertu 100mg) to treat adult patients with unresectable or metastatic Non-small cell lung cancer (NSCLC) whose tumors have activated HER2 (ERBB2) mutations and who have received prior systemic therapy, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has recommended the firm to submit the safety and efficacy data of Indian Patients for the proposed indication.

This came after the firm presented the proposal for the addition of indication for Trastuzumab Deruxtecan Powder for Concentrate for Solution for Infusion (Enhertu 100mg) under the category of life-threatening and unmet need in the country with the request for the waiver of the local clinical trial.
The proposed additional indication is “for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations and who have received prior systemic therapy.”

Trastuzumab is a monoclonal antibody against human epidermal growth factor receptor 2 (HER2). Trastuzumab binds to an extracellular domain of this receptor and inhibits HER2 homodimerization, thereby preventing HER2-mediated signaling.

Trastuzumab is a biologic agent primarily used in the treatment of HER2-positive breast cancer. It may be used as adjuvant therapy for localized disease or as first-line therapy for metastatic disease.

Trastuzumab deruxtecan binds to HER2 found on malignant cells, it is internalized and linker cleavage occurs through the actions of lysosomal enzymes. After it is released through cleavage, DXd causes targeted DNA damage and apoptosis in cancer cells, due to the ability to cross cell membranes.

At the recent SEC meeting for Oncology and Hematology held on the 7th and 8th of December 2023, the expert panel reviewed the proposal presented by the drug major AstraZeneca for the addition of indication for Trastuzumab Deruxtecan Powder for Concentrate for Solution for Infusion (Enhertu 100mg).

The committee noted that India is part of an ongoing Phase III global clinical trial.
After detailed deliberation, the committee recommended that the firm should submit the safety and efficacy data of Indian patients for the proposed indication before the committee for consideration of the additional indication.

Powered by WPeMatico

Metoclopramide may decrease need for second look Endoscopic Visualization in Active Upper GI Bleeding

In a recent breakthrough study conducted between April 2021 and October 2022, researchers delved into the effectiveness of metoclopramide in improving gastric visualization for patients experiencing active upper gastrointestinal bleeding (UGIB). They found that Metoclopramide did not significantly enhance endoscopic visualization overall but notably reduced the need for a second-look esophagogastroduodenoscopy (EGD) in patients with active UGIB.

The trial results were published in ‘The American Journal of Gastroenterology.’

The 2021 ACG Guidelines proposed the administration of intravenous (IV) erythromycin before endoscopy as a means to improve the endoscopic view and decrease the necessity for repeat procedures in individuals with upper gastrointestinal bleeding (UGIB). However, there is limited evidence regarding the use of IV metoclopramide, a more readily available option, particularly in patients experiencing ‘active’ UGIB. Hence, researchers from Thailand conducted a double-blind, double-center randomized controlled trial to assess the effectiveness of metoclopramide in enhancing gastric visualization for individuals with active UGIB.

The trial conducted between April 10, 2021, and October 8, 2022, enrolled patients with active UGIB, identified by hematemesis or the presence of fresh blood in the nasogastric tube. Participants were randomly assigned in a concealed 1:1 allocation to receive either metoclopramide or a placebo. The primary outcome measured was ‘adequate visualization’ determined by objective endoscopic visualized gastroduodenal scores (EVS). Secondary outcomes included the mean difference in EVS, duration of esophagogastroduodenoscopy (EGD), immediate hemostasis, the necessity for a second look EGD, units of blood transfusion, length of hospital stay, and 30-day rebleeding rate.

Findings:

  • Out of the 68 eligible patients, three from each group were excluded due to protocol violations.
  • The final analysis included 62 patients with 31 each in the metoclopramide group and the placebo group.
  • There were 77.4% of patients with adequate visualization in the metoclopramide group and 61.6% in the placebo group (odds ratio 2.16 [0.71-6.58], p = 0.16).
  • metoclopramide group reported a significantly lesser need for a second look EGD within 72 hours (3.2% vs. 22.6%, odds ratio 0.11 [0.01-0.99], p = 0.02).
  • Other secondary outcomes did not show considerable differences. However, in a subgroup analysis focusing on gastric lesions, metoclopramide demonstrated a remarkable improvement in the rate of adequate visualization (92.9% vs. 50%, odds ratio 13 [1.32-128.10], p = 0.03) and mean EVS at the fundus (1.79±0.42 vs. 1.29±0.72; p = 0.03).

In conclusion, while metoclopramide did not significantly enhance endoscopic visualization overall, it emerged as a promising contender in reducing the need for a second look at EGD, particularly in cases of active UGIB. The study’s findings provide valuable insights into potential advancements in the treatment of upper gastrointestinal bleeding, paving the way for more targeted and effective interventions in the future.

Take home message:

  • This was a double-blind, randomized, placebo-controlled trial that evaluated the effectiveness of metoclopramide for gastric visualization in patients with active upper gastrointestinal bleeding (UGIB). A total of 62 patients were randomized 1:1 to metoclopramide (n = 31) or placebo (n = 31). Overall, metoclopramide was no better than placebo for improving endoscopic visualization for all active UGIB lesions. However, it improved endoscopic visualization and decreased the need for second-look esophagogastroduodenoscopy in a subgroup of patients with active UGIB owing to gastric lesions.
  • These results should be interpreted with caution because the positive effect of metoclopramide on improving endoscopic visualization and decreasing the need for second-look esophagogastroduodenoscopy within 72 hours was based on a subgroup analysis.

Further reading: Vimonsuntirungsri et al. The efficacy of metoclopramide for gastric visualization by endoscopy in patients with active upper gastrointestinal bleeding: double-blind randomized controlled trial. The American Journal of Gastroenterology. DOI: 10.14309/ajg.0000000000002620

Powered by WPeMatico

Delhi Vigilance Dept calls for CBI probe into suspected spurious drugs

The Delhi government’s Directorate of Vigilance has sent the matter of suspected spurious drugs to the Union Home Ministry, urging a thorough investigation by the Central Bureau of Investigation (CBI).

The Directorate of Vigilance, in a formal letter to the Union Home Ministry on Thursday, said, “Assigning the matter if reported supply of not of standard quality drugs to hospital of Government of National Capital Territory of Delhi (GNCTD) to CBI.”

For more details, check out the link given below:

Delhi Vigilance Dept Sends Suspected Spurious Drugs Matter To Health Ministry, Urges CBI Probe

Powered by WPeMatico

WBCERC has no authority to adjudicate Medical Negligence Cases: Calcutta High Court

Kolkata: In a major decision, the Calcutta High Court bench has clearly iterated that matters concerning the issues of medical negligence cannot be adjudicated by the West Bengal Clinical Establishment Regulatory Commission (WBCERC).

Clarifying its stand in this regard, the HC bench comprising Justice Arijit Banerjee and Justice Apurba Sinha Ray noted, “The negligence in detection of diseases and the allegation of not giving proper medicines to the patient and further improper diagnosis of the diseases are all matters or issues of medical negligence. Therefore, the said issues cannot be adjudicated by the Commission.”

These observations were made by the Court while dismissing an order by WBCERC asking B.M. Birla Heart Research Centre to pay Rs 20 lakh compensation to the son of a deceased patient for “serious lack and deficiency in patient care service” during the treatment.

The Division bench, while dismissing the order of a single bench that upheld the WBCERC order in the matter, clearly stated that WBCERC cannot adjudicate medical negligence cases adding that appropriate forum for cases of medical negligence is NMC/state medical councils.

“….we make it clear that the complainant/aggrieved persons is/are at liberty to agitate all the issues regarding the medical negligence and deficient patient care service before the appropriate forum under the National Medical Commission Act, since the Indian Medical Council Act, 1956 has been repealed. In the event, the complainant approaches the forum as indicated above, such authority shall dispose of the matter without being influenced by any of the observations made in this judgment,” the bench mentioned in the order.

History of the case: 

The matter concerned a patient who was admitted to BMBHRC in 2017 at CCU with chest pain along with shortness of breath and fever for three days. She was a known patient of hypertension and was having rheumatoid arthritis along with DMARD and suspected to have Acute Coronary Syndrome (ACS)(N Stemi). WBCERC started considering the matter based on a complaint filed by the patient’s son after the patient died during treatment.

There were several allegations regarding the treatment of the patient. It was alleged that the doctor having only an MBBS degree conducted Echocardiography on the patient. Further, it was alleged that there was an unnecessary delay on the part of the treating doctors and the hospital to shift the patient to a multi-speciality hospital.

After considering relevant reports from the erstwhile Medical Council of India, West Bengal State Medical Council, and other materials on record, WBCERC concluded that even though the Commission refrained from dealing with the alleged medical negligence part of the matter, it found serious lack and deficiency in patient care service from the side of BMBHRC, and accordingly, it directed the latter institute to pay Rs 20 lakh compensation. While considering the plea challenging the WBCERC order, the Single Judge bench dismissed the plea holding that the conclusion arrived by the Commission was correct and justified.

Approaching the Division bench, the counsel for the hospital argued that even though the complaint was lodged alleging ‘deficiency in service’ and ‘negligent treatment’ against the hospital and its doctor (Dr. Dutta), the Commission went on to adjudicate the complaint in violation of provision of section 38(iii) of the West Bengal Clinical Establishment (Registration, Regulation, and Transparency) Act, 2017 which prohibits the Commission to adjudicate any issue of medical negligence.

Further, the counsel argued that even though WBCERC held that one of the doctors, Dr Giri, an MBBS with PGDCC from IGNOU was not competent enough to conduct and interpret the data of echocardiography, while the replies of the M.C.I pursuant to queries under the Right to Information Act, revealed that the Post Graduate Medical Education Regulation, 2000 is silent about such query. 

Apart from this, the counsel also highlighted the fact that in order to properly adjudicate the issue, the Commission ought to have a member who was a Cardiologist for proper understanding of the case and to come at a correct decision as to whether the Echo-Cardiogram findings indeed had any relation to the death of the patient. No expert opinion from an independent cardiologist was also not sought.

Courts observations

Making several remarks on the issue of medical negligence on the case, the court noted that  WBCERC has no authority to observe that the concerned doctor was not qualified to conduct and interpret the ECG report.

“The negligence in detection of diseases and the allegation of not giving proper medicines to the patient and further improper diagnosis of the diseases are all matters or issues of medical negligence. Therefore, the said issues cannot be adjudicated by the Commission. There was no sufficient material on record to hold, that delay, if any, was caused only because of the clinical establishment and not from the side of the patient party. Furthermore, there is no material to show how the patient party was misguided by the clinical establishment.”

“…the issues of medical negligence and the issues of alleged deficient patient care services are so inextricably mingled up, the issues of patient care service cannot be taken up separately. In other words the issues of patient care service are dependent upon the competence of the concerned doctor or the ECG technician, and such technical issues which are required to be addressed before the specialised branch, could not be adjudicated by the Hon’ble Commission. The instant fact was also not considered by the Learned Single Judge. There are sufficient materials on record which suggest that there are certain palpable wrongs in the Hon’ble Commission’s order which were not properly addressed by the Learned Single Judge,” 

 The bench opined that unless the Medical Council of West Bengal declared through specific and appropriate disciplinary action that Dr. Giri was an unqualified doctor, the Commissioner had no authority to declare Dr. Giri was unqualified to perform the ECG or to interpret the findings.

“It may happen that if the State Medical Council initiates a disciplinary proceeding regarding his alleged professional misconduct and Dr. Giri is able to prove before the disciplinary committee of the State Medical Council that he is entitled to practice cardiology and is further entitled to conduct ECG and interpret the report, he may be exonerated from the said allegation,

“When specific provisions have been made to enquire about the alleged professional misconduct by a specialised body, the Commission cannot enter into the arena of that specialised body which has been rightly kept reserved for the medical professionals. It is further found from Regulation 8.6 that such professional’s incompetence can only be judged by a peer group as per guidelines prescribed by Medical Council of India. Therefore, there are specific provisions for dealing with such alleged professional misconduct of a medical practitioner. Therefore, unless the State Medical Council or National Medical Commission declares that the concerned doctor is not qualified to perform ECG, the Commission cannot hold Dr. Giri as unqualified. In fact, Commission has no authority to declare a medical practitioner as unqualified or incompetent for lack of requisite qualifications as the same is beyond its authority,”

Referring to this, the bench noted that if the alleged incompetence of the concerned doctor is not found by the concerned SMC, it would be preposterous to say that BMBHRC engaged incompetent and unqualified doctor and is guilty of deficiency in patient’s care service.

In respect of the PG Diploma in Clinical Cardiology from IGNOU, the bench observed that the matter is under consideration of Delhi High Court, adding that decision of whether physician is falsely claiming to be a specialist and its discretionary actions lies with the councils only

“if  it is found that if a physician falsely claims to be a specialist he is guilty of misconduct as laid down in 7.20 under chapter 7 of the Regulations, 2002. But to declare a physician to be guilty of professional misconduct under 7.20 as aforesaid, the disciplinary action is required to be taken by the concerned Medical Council and after giving reasonable opportunity of hearing to such medical practitioner if the said medical council finds that he is guilty of committing professional misconduct, the said Council shall punish the delinquent by way of removing his name from the State Register permanently or for a limited period.”

The bench opined that instead of considering the matter, WBCERC should have referred the matter to SMC or NMC for consideration. The court noted,

“…without going into the said question the Commission ought to have relegated the matter to the State Medical Council or National Medical Commission for consideration. If the State Medical Council or the National Medical Commission found that Dr. Giri is unqualified then BM Birla Heart Research Institute could be held to be responsible for deficient patient care service for engaging unqualified doctor. But if the State Medical Council or the National Medical Council did not find Dr. Giri as unqualified then the charges against BM Birla Heart Research Institute for providing deficient patient care service would not have stood as regards appointment of Dr. Giri.”

Finally, the bench once again clarified that WBCERC can determine its own procedure for adjudicating the allegations under the Act, 2017. “But that does not mean that the Commission can ignore the fundamental principles of judicial procedure in adjudicating the same. From the judgement of the Commission we found several discrepancies which were required to be addressed by the Learned Single Judge,” it noted.

The court elaborated on the role of WBCERC and noted,

“…the Commission has a duty under the law to see that unqualified doctors or technicians are not engaged in the clinical establishment but this duty of the Commission has to be discharged very cautiously and circumspectively.”

Therefore, setting aside the WBCERC and the single bench order, the Division bench noted,

“…the issues of medical negligence and the issues of alleged deficient patient care services are so inextricably mingled up, the issues of patient care service cannot be taken up separately. In other words the issues of patient care service are dependent upon the competence of the concerned doctor or the ECG technician, and such technical issues which are required to be addressed before the specialised branch, could not be adjudicated by the Hon’ble Commission. The instant fact was also not considered by the Learned Single Judge. There are sufficient materials on record which suggest that there are certain palpable wrongs in the Hon’ble Commission’s order which were not properly addressed by the Learned Single Judge.”

“The appellant is also given liberty to withdraw the sum of Rs. 15,00,000/- (Fifteen Lakhs) deposited with the office of the Registrar General, High Court at Calcutta in accordance with law, after the expiry of the period of appeal,” it ordered.

To view the order, click on the link below:

https://medicaldialogues.in/pdf_upload/calcutta-hc-228938.pdf

Powered by WPeMatico

Paramedic practicing in rural area seeks registration of his clinic, gets slammed by Karnataka HC

The Karnataka High Court recently observed that it is time to take action against people who are practicing medicine without qualification. With this, the bench has dismissed a petition to quash an endorsement by the state authorities declining to issue a registration certificate under the Karnataka Private Medical Establishments Act to a man who pursued para-medical studies and was practicing as a doctor for several years at his clinic.

For more details, check out the link given below:

Paramedic Practicing In Rural Area Seeks Registration Of His Clinic, Gets Slammed By Karnataka HC

Powered by WPeMatico

Class 10th passouts eligible to pursue ayurveda course, new regulations call for NEET Pre-Ayurveda

With the publication of the new National Commission for Indian System of Medicine (National Examinations for Indian System of Medicine) Regulations, 2023, now students can pursue pre-Ayurveda courses even after passing their tenth standard exam.

These new regulations, which were published in the official Gazette on 20.12.2023, mentioned that there shall be a separate National Eligibility-cum-Entrance Test for admission to Pre-Ayurveda courses.

For more details, check out the link given below:

Now, Class 10th Passouts Eligible For Entering Ayurveda Course, New Regulations Call For NEET Pre-Ayurveda

Powered by WPeMatico

Bayer Pharma gets CDSCO Panel nod to study Asundexian 50mg tablets

New Delhi: Bayer Pharmaceutical has got approval from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) to conduct the phase III clinical trial of Asundexian (BAY 2433334) tablets.

However, this approval is subject to the condition that clarity on PFO (patent foramen ovale) and arterial episode findings in Echo as embolic or nonembolic shall be mentioned in the inclusion criteria.

This came after Bayer Pharmaceutical presented the Phase III Clinical study protocol no. 20604.

Asundexian (BAY 2433334) is an orally active coagulation factor Xia (FXIa) inhibitor. Asundexian binds directly, potently, and reversibly to the active site of FXIa and thereby inhibits its activity.

Asundexian inhibited human FXIa with high potency and selectivity. It reduced FXIa activity, thrombin generation triggered by contact activation or low concentrations of tissue factor, and prolonged activated partial thromboplastin time in humans, rabbits, and various other species, but not in rodents.

At the recent SEC meeting for Neurology and Psychiatry held on 12th and 13th December 2023, the expert panel reviewed the Phase III clinical study protocol of the anticoagulant Asundexian presented by Bayer Pharmaceutical.

After detailed deliberation, the committee recommended the grant of permission to conduct the trial as presented by the firm with conditions that clarity on PFO and arterial episode findings in Echo as embolic or non-embolic shall be mentioned in the inclusion criteria.

Also Read:AstraZeneca Gets CDSCO Panel Nod for Enhertu 100mg for additional indication of breast cancer

Powered by WPeMatico

Delhi reports first Covid JN.1 case

Following the identification of the first case of the Covid-19 sub-variant JN.1 in the national capital, the All India Institute of Medical Sciences (AIIMS) in Delhi has released guidelines for managing suspected or positive Covid patients in hospitals. In response to a meeting with department heads, the AIIMS Delhi Director has directed the establishment of a Covid screening Outpatient Department (OPD) within the emergency department. Additionally, 12 beds in a designated ward will be reserved for the hospitalization of critically ill patients. AIIMS Delhi has also mandated Covid testing for individuals exhibiting Severe Acute Respiratory Infections (SARI) symptoms.

The directives include the allocation of Covid management provisions in all AIIMS departments and the earmarking of specific beds for serious cases. A screening OPD in the Emergency Department will assess patients for Covid-like symptoms, and a new private ward will accommodate Covid-positive Employees Health Scheme (EHS) beneficiaries. Furthermore, the installation of advanced air purifying filters is underway.

For more news & updates, check out the link given below:

https://medicaldialogues.in/

Powered by WPeMatico

Revise BE study protocol: CDSCO Panel tells Akum Pharma on FDC of Chlorthalidone, Cilnidipine, Bisoprolol film-coated tablet

New Delhi: Citing that individual and innovators’ products should be taken as a reference product in the proposed bioequivalence study protocol, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has opined the drug major Akum Pharmaceutical to revise the bioequivalence (BE) study protocol for Chlorthalidone IP 6.25mg plus Cilnidipine IP 5mg plus Bisoprolol Fumarate IP 5mg film-coated tablet.

This came after Akum Pharmaceutical presented the proposal along with the BE study protocol before the committee.

Chlorthalidone is a diuretic used to treat hypertension or edema caused by heart failure, renal failure, hepatic cirrhosis, estrogen therapy, and other conditions.

Chlorthalidone is a thiazide-like diuretic used for the treatment of hypertension and the management of edema caused by conditions such as heart failure or renal impairment. Chlorthalidone improves blood pressure and swelling by preventing water absorption from the kidneys through inhibition of the Na+/Cl− symporter in the distal convoluted tubule cells in the kidney.

Cilnidipine is a dihydropyridine calcium channel blocker with action on both N- and L-type calcium channels used to treat hypertension.

Cilnidipine acts on the L-type calcium channels of blood vessels by blocking the incoming calcium and suppressing the contraction of blood vessels, thereby reducing blood pressure. Cilnidipine also works on the N-type calcium channel located at the end of the sympathetic nerve, inhibiting the emission of norepinephrine and suppressing the increase in stress blood pressure.

Bisoprolol is a cardioselective β1-adrenergic blocking agent used to treat high blood pressure. It is considered a potent drug with a long half-life that can be used once daily to reduce the need for multiple doses of antihypertensive drugs.

Bisoprolol is indicated for the treatment of mild to moderate hypertension. It may be used off-label to treat heart failure, atrial fibrillation, and angina pectoris.

At the recent SEC meeting for Cardiovascular and Renal on 6th and 7th December 2023, the expert panel reviewed the proposal along with the BE study protocol of the Chlorthalidone plus Cilnidipine plus Bisoprolol Fumarate film-coated tablet which was presented by the drug major Akum Pharmaceutical.
After detailed deliberation, the committee recommended that the BE protocol be revised. Furthermore, the expert panel suggested that the individual and innovators’ products should be taken as a reference product in the proposed BE study protocol.
Accordingly, the committee stated that the revised BE study protocol should be submitted to CDSCO for review by the committee.

Powered by WPeMatico

Cell, gene therapy to rule pharma sector in 2024: Report

New Delhi: Cell and gene therapy (CGT) will have the greatest impact on the pharmaceutical industry in 2024, according to a report on Thursday.

The report by GlobalData, a data and analytics company, is based on a survey of 115 healthcare industry professionals.

It revealed that 18 per cent of industry professionals were convinced that CGT will dominate as the most important trend in pharma next year. This was followed by personalised/precision medicine (16 per cent).

“Cell and gene therapies are gradually becoming more important focus areas within the healthcare industry and their full potential is still unrealised. While this is a relatively new area, with the first autologous dendritic cell therapy Provenge approved in 2010 for prostate cancer, these therapies promise life-changing treatments for a broad spectrum of complex diseases ranging from genetic conditions to cancers,” said Urte Jakimaviciute, Senior Director of Market Research at GlobalData, in a statement.

Although GlobalData anticipates cell and gene therapies to become an established treatment modality in the years to come, higher development and production costs, the risk of clinical trial failures, and intensifying pricing and reimbursement pressures will continue to place further stress on these innovations.

“The industry may try to offset the high development costs by outsourcing. One of the recent examples is Bayer’s announcement of a cooperation with Shanghai Pharmaceuticals China in November 2023 to set up its first Chinese lab for CGT and cancer drug development. With lower R&D development costs than in advanced markets, countries like China are becoming attractive markets for the development of CGT, and therefore may emerge as strong competitors of overseas-made CGT,” Jakimaviciute said.

The report estimates that the global CGT market is projected to reach $80 billion by 2029.

Oncology is expected to continue its lead as the indication and area of major development for cell and gene therapies, accounting for 44 per cent of the CGT market by 2029.

“Even though cell and gene therapies are mainly approved for the use in the oncology space, the versatility of these therapies means that they can be used in both acquired and inherited diseases. Other therapeutic areas that can benefit the most from CGT include neurodegenerative, autoimmune, and cardiovascular diseases,” Jakimaviciute said.

Powered by WPeMatico