FDA fast tracks investigational gene therapy for heart failure

The US Food and Drug Administration (FDA) has granted Fast Track designation to invesigational gene therapy AB-1002 for treatment of congestive heart failure (CHF).AB-1002 is an investigational one-time gene therapy designed to inhibit the action of protein phosphatase 1, which has been linked to heart failure.

Inhibiting the function of this protein, which is linked to congestive heart failure (CHF), could potentially lead to a therapeutic effect on the heart.

“The FDA Fast Track Designation for AB-1002 is an important accomplishment for the clinical development of this program and highlights our goal of potentially bringing effective treatments to patients with advanced congestive heart failure,” said Canwen Jiang, MD, PhD, Chief Development Officer and Chief Medical Officer, AskBio. “We look forward to completing our Phase II GenePHIT clinical trial, which is currently enrolling patients with severe heart failure, and are committed to exploring the full potential of AB-1002 for the treatment of this devastating disease.”

The FDA Fast Track Program is designed to facilitate the development and expedite the review of new therapeutics that are intended to treat serious conditions and fill unmet medical needs. The purpose of the Program is to get important new therapeutics to patients earlier. Therapeutics that receive this designation benefit from eligibility for more frequent meetings with the FDA to discuss the development plan and, if relevant criteria are met, eligibility for Accelerated Approval and Priority Review.

“The Fast Track Designation for AB-1002 emphasizes the need to rapidly advance new therapeutic modalities such as gene therapy for people living with congestive heart failure,” said Christian Rommel, PhD, Head of Research and Development at Bayer’s Pharmaceuticals Division. “This designation underpins the potential of AB-1002 to address currently high unmet medical need, and we are excited about the opportunity to accelerate its development.”

AB-1002 is an investigational gene therapy that has not received marketing authorization, and its efficacy and safety have not been established or fully evaluated. AskBio is currently enrolling patients in the Phase II GenePHIT (Gene PHosphatase Inhibition Therapy) trial of AB-1002 (also known as NAN-101) for the treatment of CHF.

About GenePHIT

GenePHIT is a Phase II adaptive, double-blinded, placebo-controlled, randomized, multi-center trial to evaluate the safety and efficacy of the one-time administration of AB-1002, via antegrade intracoronary artery infusion, in males and females age >18 years with non-ischemic cardiomyopathy and New York Heart Association (NYHA) Class III heart failure symptoms. Subjects are randomized into one of three treatment groups in a 1:1:1 fashion to either low dose, high dose, or placebo. Primary outcome measures include cardiovascular related death and change from baseline in NYHA classification, left ventricular ejection fraction (LVEF), peak oxygen uptake (pVO2), and Six Minute Walk Test (6MWT). For more information, please visit clinicaltrials.gov or visit askbio.com.

About Congestive Heart Failure

Heart failure occurs when the heart cannot pump blood efficiently enough to meet the body’s needs, including providing sufficient oxygen to the organs. Congestive heart failure results in the slowing of the blood flow out of the heart, which causes the blood returning to the heart through the veins to back up. This causes congestion in the body’s tissues. Symptoms include swelling in the legs and ankles. Sometimes, fluid collects in the lungs and interferes with breathing. Approximately 26 million people worldwide are living with congestive heart failure.

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Patients of autoimmune liver disease treated with immune suppressants have lower prevalence of apical periodontitis: Study

Patients of autoimmune liver disease treated with immune suppressants have a lower prevalence of apical periodontitis suggests a study published in the Journal of Endodontics.

Autoimmune liver diseases (ALDs) are chronic conditions generated by an immune-mediated auto-aggressive inflammatory reaction in genetically susceptible individuals. The purpose of this study was to evaluate the prevalence of apical periodontitis in patients suffering from ALDs, in treatment with the immune-suppressants glucocorticoids, azathioprine, and/or ursodeoxycholic acid. The Autoimmune liver diseases group included 46 patients (11 men and 35 women, average age: 57.9 ± 11.8 years) and 1186 teeth. The control (C) included 50 healthy patients (15 men and 35 women, average age: 58.6 ± 10.4 years) and 1251 teeth), under no medications. Demographic data, and medical, pharmacological, and dental history, were recorded. Dental and radiographic examinations were performed, presence of apical periodontitis, periapical index score, DMFT, quality of restoration, and root canal treatment were evaluated. The influence of the medications assumed by the patients on the prevalence of apical periodontitis was also tested. Results: The prevalence of apical periodontitis was significantly lower in Autoimmune liver diseases than in C, at patient (p=.019), and tooth level (p=.005). (p=.015). Smoking and age were associated with a significant increase in apical periodontitis in cases and controls (p=0.045, and p=0.001). In both groups, endodontically treated teeth showed a higher prevalence of apical periodontitis. Considering all the limitation due to the observational nature of the study, the patients affected by autoimmune liver diseases, and in treatment with immune-suppressors (often associated with immune-modulators), were found to exhibit lower prevalence of apical periodontitis.

Reference:

Ideo F, Niazi S, Chessa L, Miglianti M, Bardini G, Mannocci F, CottiDDS E. Prevalence of apical periodontitis in patients with autoimmune liver diseases under immune suppressants and immune modulators: a cross-sectional study. J Endod. 2024 Mar 23:S0099-2399(24)00165-1. doi: 10.1016/j.joen.2024.02.026. Epub ahead of print. PMID: 38527610.

Keywords:

Patients, autoimmune, liver disease, immune suppressants, lower prevalence, apical periodontitis, study, Journal of Endodontics, Ideo F, Niazi S, Chessa L, Miglianti M, Bardini G, Mannocci F, CottiDDS E

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Bond policy issue raised at NHRC meeting, Is abolishing likely?

New Delhi: The issue of Bond policy was raised during the meeting held today by the National Human Rights Commission (NHRC). In the meeting, the National Medical Commission (NMC) officials including the Chairman Dr B Gangadhar and Secretary Dr B Srinivas were also present and the Commission expressed its plans regarding the bond policy in India.

The NHRC meeting was conducted to discuss the issues of mental health and mental well-being of medical students across the country. 

Speaking about the session, the National Chairman of the Federation of All India Medical Association (FAIMA), Dr. Rohan Krishnan, who also participated in the meeting, told Medical Dialogues, “The major statement that was made was that NMC is planning for a bond-free India. FAIMA has worked very hard on this for several years. FAIMA demanded that the bond policy should be revised and the States where there is a scarcity of doctors, in those States also bond policy should be reconsidered. All these things were discussed in the meeting.”

Meanwhile, notifying about the meeting, NHRC mentioned in an X (formerly Twitter) post, “NHRC core group meeting in hybrid mode on health and mental health begins. It focuses on discussing issues of bonds in medical colleges, the rights of patients, the rights of doctors, and problems in disbursal of stipend to doctors.”

Also Read: Breaking News: NMC Asks States to do Away with Seat leaving Bond

Apart from the NMC officials, the meeting was also attended by the stakeholders from the Health Department, Health Secretary, Chairman of NHRC, representatives of the Indian Medical Association (IMA), Federation of Resident Doctors Association (FORDA), representatives from the United Doctors Front Association (UDFA).

Dr. Rohan Krishnan informed that issues like bond policy, patient welfare, healthcare structure of the nation including what will happen in the future- all these things were discussed in the meeting.

Commenting on the issues, Dr. Rohan Krishnan told Medical Dialogues, “Mental health of the medical students across the country should be of prime concern right now, considering the fact that so many young doctors and MBBS students commit suicide being unable to deal with the immense pressure of studies and work.”

“Doing away with the seat-leaving bond can be a stepping stone in lessening the mental burden on the medical students and we appreciate the efforts of NMC in this regard,” he further added.

In an X post, Dr. Krishnan mentioned, “Took part in a meeting Organised by @India_NHRC Glad to Hear that @NMC_IND Chairman wishes to abolish bond policy pan India. Also, NMC has taken a positive stand on Stipend given to interns,PGs. However, I have again raised the issue of improvement in various aspects of healthcare for *Mental Health and Mental well being of UG and Pg Residents.”

Medical Dialogues had previously reported that earlier this year, taking cognisance of the issue of seat-leaving bond policy, NMC wrote to the Principal Secretary of Health and Medical Education of all States and Union Territories and asked them review the said policy and preferably do away with the same.

The Apex Medical Commission issued this direction after the Anti-Ragging Committee of NMC held a meeting on 9th January 2024 to address the mental health concerns of PG medical students and recommended the State/UT to review the seat leaving policy in medical colleges and to do away the same.

As an alternative, NMC recommended that the States may consider debarring the students for admission in their States for the next one year.

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SC holds Medical Negligence during Appendicitis Surgery, rejects NCDRC’s Application of Eggshell-Skull Rule

New Delhi: Setting aside the order of the National Consumer Disputes Redressal Commission (NCDRC), which had reduced the compensation awarded to a patient for medical negligence during appendicitis surgery, the Supreme Court has enhanced the amount to Rs 5 lakh. The apex court noted that the patient suffered persistently post-surgery due to a deficiency in service by the doctor and the hospital.

The treating hospital based in Mandi, Himachal Pradesh and its doctors were held negligent for leaving a needle during the surgery back in 2005. While considering the matter, the Apex Court bench of Justices Sanjay Karol and Aravind Kumar restored the order passed by the District Consumer Court after it rejected NCDRC’s decision to apply the ‘Eggshell-Skull Rule’ in the case.

“A person who has an eggshell skull is one who would be more severely impacted by an act, which an otherwise “normal person” would be able to withstand. Hence the term eggshell to denote this as an eggshell is by its very nature, brittle. It is otherwise termed as “taking the victim as one finds them” and, therefore, a doer of an act would be liable for the otherwise more severe impact that such an act may have on the victim,” the Supreme Court noted.

“In regard to the application of the Eggshell-Skull Rule, we may observe that the impugned judgment is silent as to how this rule applies to the present case. Nowhere is it mentioned, as to what criteria had been examined, and then, upon analysis, found to be met by the claimant-appellant for it to be termed that she had an eggshell skull, or for that matter, what sort of pre-existing condition was she afflicted by, making her more susceptible to such a reaction brought on because of surgery for appendicitis,” the Supreme Court bench observed.

The history of the case goes back to 2005, when the petitioner patient was admitted to Suket Hospital, Mandi, Himachal Pradesh and had her appendicitis removed by a senior surgeon of the hospital Dr. Chauhan. After the surgery, she was discharged. However, following this, she suffered continuous pains near the surgical site and had to get readmitted after around one month. She was discharged the next day with the assurance that no further pain would be suffered by her.

Later, she was treated by another Dr. Vaidya of Mandav Hospital, Mandi, on the reference of Dr. Chauhan. However, allegedly her suffering did not end and it continued for a period of four years.

Eventually, the patient approached the Post Graduate Institute of Medical Science, Chandigarh and after investigation, it was found that a 2.5 cm foreign body (needle) was “present below the anterior abdominal wall in the preveside region just medial to previous abdominal scar (Appendectomy)” for which a further surgery was required for its removal.

Thereafter, alleging negligence by Suket Hospital, the patient filed a consumer complaint and claimed compensation of Rs 19,80,000 for the “huge pain and spent money on treatment”.

While considering the case, the District Consumer Forum, Mandi noted that the patient had to suffer physical pain for more than five years due to negligence and noting this, the Forum awarded Rs 5 lakh lump sum compensation to the Complainant.

The order was challenged before the State Commission, which noted that the “needle was not left at the site of surgery, at the Hospital of the appellants, when the complainant was operated for removal of appendicitis, yet from an overall reading of the pleadings and evidence on record, it can be said that surgery conducted at the clinic of the appellants, was the cause of pain…”

Therefore, the State Commission reduced the amount of compensation and directed the hospital and its doctors to pay Rs 1 lakh compensation for the physical pain, mental agony and expenses incurred by the appellant.

Consequently, the matter came to be considered by the NCDRC bench, which observed that the post-operative care provided by the hospital and doctors was casual and fell short of the standard of medical care. It opined that they had failed to investigate the non-healing surgical wound thereby constituting a deficiency in service. 

The egg-skull rule was applied to hold an individual liable for all consequences of their act. The compensation awarded by the State Commission was enhanced to Rs.2,00,000. Therefore, challenging the NCDRC order, the appellant approached the Supreme Court bench seeking enhancement of the compensation.

Taking note of the earlier orders passed in the case, the Supreme Court bench observed, “The factum of negligence on the part of the respondent Hospital as well as respondent No.2 has not been doubted, across fora. Although the State Commission had differed with the District Forum on the presence of the needle, the NCDRC, in para 5 of the impugned judgment and order, found the medical record to testify to the presence of a needle in the abdomen and also found that the respondent Hospital was found wanting in terms of post-operative care.”

The Apex Court noted that the primary ground alleged, in submitting that the finding of medical negligence is unjustified, was that there has been a recorded gap of time where the appellant did not suffer from any pain (1½ years). However, the bench noted that NCDRC observed her period of suffering to be more than 5 years,

“implying thereby that the gap in suffering aspect has not been accepted. No material has been placed before us to take a different view therefrom…we are only required to examine the sufficiency of compensation as awarded by way thereof. The same, though, cannot be appositely done without having appreciated pronouncements of this Court on the scope and purpose of the Consumer Protection Act; medical negligence; and compensation in such cases as also, the rule of tort law known as the ‘eggshell skull’ rule.”

In respect of the eggshell skull rule, which was applied by NCDRC, the Supreme Court bench noted that this rule holds the injured liable for damages that exceed the amount that would normally be expected to occur. It is a common law doctrine that makes a defendant liable for the plaintiff’s unforeseeable and uncommon reactions to the defendant’s negligent or intentional tort.

To put it simply, a person having an eggshell skull would be the one who would be more severely impacted by an Act, which an otherwise “normal person” would be able to withstand. “Hence the term eggshell to denote this as an eggshell is by its very nature, brittle. It is otherwise termed as “taking the victim as one finds them” and, therefore, a doer of an act would be liable for the otherwise more severe impact that such an act may have on the victim,” explained the Supreme Court.

The Supreme Court bench noted that in order to invoke and apply this rule appropriately, the person in whose case an adjudicatory authority applies must have a pre-existing condition falling into either of the four following categories.

It was noted by the Apex Court that the jurisprudence of the application of this rule, as has developed, (needless to add, in countries other than India) has fit into four categories- first, when a latent condition of the plaintiff has been unearthed; second, when the negligence on the part of the wrongdoer re-activates a plaintiff’s pre-existing condition that had subsided due to treatment; third, wrongdoer’s actions aggravate known, pre-existing conditions, that have not yet received medical attention; and fourth, when the wrongdoer’s actions accelerate an inevitable disability or loss of life due to a condition possessed by the plaintiff, even when the eventuality would have occurred with time, in the absence of the wrongdoer’s actions.

“As these categories and, the name of the rule itself suggest, the persons to whose cases this rule can be applied, are persons who have pre-existing conditions,” noted the Supreme Court bench.

Referring to previous legal precedent set by the courts across the world, the Supreme Court bench noted,

“we find the manner in which compensation stood reduced by the State Commission as also the NCDRC, vis-à-vis the District Forum to be based on questionable reasoning.”

The Supreme Court bench noted that the State Commission recognized that the appellant was not treated “with the care expected at a medical clinic”, and she had been suffering from persistent pain right from 2005 until December 2008, and the post-surgical care was deficient and “yet found it appropriate to reduce the compensation to a mere Rs.1 lakh. This clearly is not in line with the balance of interests required to be borne in mind while determining compensation.”

Similarly, referring to the NCDRC judgment, the Apex Court observed,

“The NCDRC observed that the claimant-appellant’s treatment at the respondent-Hospital was ‘casual’; that the excuse of having sought treatment at other hospitals was not available to the respondents and that she had suffered pain for more than 5 years apart from the case having been dragged on for more than a decade, and yet lumpsum compensation was only Rs.2 lakhs.”

“How could such compensation be justified, after observations having been made regarding the service rendered by the Hospital, being deficient, and the continuous pain and suffering on the part of the claimant-appellant, is something we fail to comprehend. Compensation by its very nature, has to be just. For suffering, no part of which was the claimant-appellant’s own fault, she has been awarded a sum which can, at best, be described as ‘paltry’,” it further noted.

In respect of the application of the Eggshell-Skull Rule, the bench observed that the judgment did not mention as to what criteria had been examined, and after analysis, was found to be met by the claimant-appellant for it to be termed that she had an eggshell skull. The NCDRC order did not specify what sort of pre-existing condition was she afflicted by, making her more susceptible to such a reaction brought on because of surgery for appendicitis, noted the Apex Court.

“If we take the rule as exposited by the NCDRC, even then it stands to reason that the record ought to have been speaking of a pre-existing vulnerability or medical condition, because of which the victim may have suffered ‘unusual damage’. However, none of the orders – be it District, State Commission or the NCDRC refer to any such condition,” it further noted.

With this observation, the Supreme Court bench set aside the NCDRC order and the order passed by the State Commission and restored the District Forum’s order of awarding Rs 5 lakh compensation.

The Supreme Court noted, “Considering the discussion as aforesaid, we deem it fit to set aside the Awards of the NCDRC as also the State Commission and restore the Award as passed by the District Forum, meaning thereby that a sum of Rs.5 lakhs ought to be paid expeditiously by the respondents to the appellant for being medically negligent and providing services deficient in nature. The sum of Rs.5 lakhs shall be accompanied by interest simple in nature @ 9% from the date of the award passed by the District Forum. The same be paid within a period of four weeks from the date of this judgment. Additionally, a cost of Rs.50,000/- be paid in terms of the cost of litigation. The appeal is accordingly allowed.”

To view the order, click on the link below:

https://medicaldialogues.in/pdf_upload/supreme-court-eggshell-skull-rule-236841.pdf

Also Read: Mens rea as intent not necessary in Medical negligence cases, Following Established procedure is: Supreme Court

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GSK Gets CDSCO Panel Nod to Study antimalarial drug Tafenoquine

New Delhi: The pharmaceutical major GSK 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 the antimicrobial drug Tafenoquine Tablets 50 mg /150 mg, used to prevent and to treat malaria.

However, this approval is subject to the condition that GSK should submit Independent data monitoring committee (IDMC) recommendations along with interim analysis reports of pediatric participants 12 to 18 years of age as per the protocol.

This came after the drug maker GSK presented the proposal along with the Phase III clinical trial protocol of Tafenoquine tablets 50mg/150 mg before the committee.

Tafenoquine belongs to a group of medicines, called antiprotozoals. It works by treating malaria, a red blood cell infection transmitted by the bite of a mosquito. It also prevents the development of the blood forms of the parasite, which are responsible for the relapse.

The mechanism of action of tafenoquine is not well established but studies have reported a longer and more effective action when compared to primaquine. The active moiety of tafenoquine, 5,6 ortho quinone tafenoquine, seems to be redox cycled by P. falciparum which is upregulated in gametocytes and liver stages. Once inside, the oxidated metabolite produces hydrogen peroxide and hydroxyl radicals. It is thought that these radicals lead to the parasite’s death.

On the other hand, tafenoquine inhibits heme polymerase in the blood stage of parasites which explains the activity against the blood stages of parasites.

At the recent SEC meeting for Antimicrobial and Antiviral held on 10th April 2024, the expert panel reviewed the proposal along Phase III clinical trial protocol of Tafenoquine tablets 50mg/150 mg before the committee.

After detailed deliberation, the committee recommended the grant of permission to conduct the Phase III clinical trial as per the protocol presented, subject to the condition that the firm should submit IDMC recommendations along with an interim analysis report of pediatric participants 12 to 18 years of age as per the protocol to CDSCO for further review by the committee for extension of the study.

Also Read: Dr Reddy’s Laboratories gets CDSCO Panel Nod To Import and Market Toripalimab 240mg solution for infusion

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Survey finds loneliness epidemic runs deep among parents

A new national survey conducted by The Ohio State University Wexner Medical Center finds that a broad majority of parents experience isolation, loneliness and burnout from the demands of parenthood, with many feeling a lack of support in fulfilling that role.

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The consumption of certain food additive emulsifiers could be associated with the risk of developing type 2 diabetes

In Europe and North America, 30 to 60% of dietary energy intake in adults comes from ultra-processed foods. An increasing number of epidemiological studies suggest a link between higher consumption levels of ultra-processed foods with higher risks of diabetes and other metabolic disorders.

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Perinatal transmission of HIV can lead to cognitive deficits

Perinatal transmission of HIV to newborns is associated with serious cognitive deficits as children grow older, according to a detailed analysis of 35 studies conducted by Georgetown University Medical Center neuroscientists. The finding helps pinpoint the geographic regions and factors that may be important for brain development outcomes related to perinatal HIV infection: mother-to-child HIV transmission during pregnancy, labor and delivery, or breastfeeding.

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Scientists explore the coupling between health span and lifespan in Caenorhabditis

A new research paper was published in Aging titled, “The coupling between healthspan and lifespan in Caenorhabditis depends on complex interactions between compound intervention and genetic background.”

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Social media use linked to tobacco initiation among youth

The tobacco industry has long appealed to youth through targeted marketing that glamorizes smoking with imagery of candy-flavored products, celebrity endorsements, social settings, and other enticing tactics. That marketing approach appears to be particularly effective on social media, according to a new study led by Boston University School of Public Health (BUSPH) researchers.

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