Leukemia Overview: Symptoms, Signs, Treatment and Causes

New Hemophilia Treatment Approved By FDA

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Today, the U.S. Food and Drug Administration approved Hympavzi (marstacimab-hncq) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A without factor VIII inhibitors or hemophilia B without factor IX inhibitors (neutralizing antibodies).

"Today's approval of Hympavzi provides patients with hemophilia a new treatment option that is the first of its kind to work by targeting a protein in the blood clotting process," said Ann Farrell, M.D., Director of the Division of Non-Malignant Hematology in the FDA's Center for Drug Evaluation and Research. "This new type of treatment underscores the FDA's commitment to advance the development of innovative, safe and effective therapies."

Hemophilia A and hemophilia B are genetic bleeding disorders caused by a dysfunction or deficiency of coagulation factor VIII (FVIII) or IX (FIX), respectively. Patients with these hemophilias are unable to clot properly and may bleed for a longer time than normal after injury or surgery. They may also have spontaneous bleeding in muscles, joints and organs, which can be life-threatening. These bleeding episodes are typically managed by either on-demand, episodic treatment or prophylaxis using products containing FVIII or FIX, or a product that mimics a factor.

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Hympavzi is a new type of drug that, rather than replacing a clotting factor, works by reducing the amount, and therefore, the activity of, the naturally occurring anticoagulation protein called tissue factor pathway inhibitor. This increases the amount of thrombin, an enzyme that is critical in blood clotting, that is generated. This is expected to reduce or prevent the frequency of bleeding episodes. 

Hympavzi's approval is based on an open-label, multi-center study in 116 adult and pediatric male patients with either severe hemophilia A or severe hemophilia B, both without inhibitors. For the first six months of this study, patients received treatment with replacement factor either on-demand (33 patients) or prophylactically (83 patients). These patients then received Hympavzi prophylaxis for 12 months. The primary measure of efficacy of Hympavzi was the annualized bleeding rates of treated bleeds. In the patients receiving on-demand factor replacement during the first six months of the study, the estimated annualized bleeding rate was 38 compared to the estimated annualized bleeding rate during treatment with Hympavzi of 3.2, showing that Hympavzi was superior to on-demand factor replacement. In the initial six-month period during which patients received prophylactic factor replacement, the estimated annualized bleeding rate was 7.85 and was 5.08 during the subsequent 12 months on Hympavzi prophylaxis, showing that Hympavzi provided similar bleeding rates.

Hympavzi comes with warnings and precautions about circulating blood clots (thromboembolic events), hypersensitivity and embryofetal toxicity.

The most common side effects of Hympavzi are injection site reactions, headache and itching (pruritis).

The FDA granted Hympavzi Orphan Drug designation for this application. 

The FDA granted the approval of Hympavzi to Pfizer Inc.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.

What Is The Infected Blood Scandal And How Much Compensation Will Victims Get?

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The government has confirmed it has set aside £11.8bn to compensate victims of the infected blood scandal.

More than 30,000 people in the UK were infected with HIV and hepatitis C after being given contaminated blood products in the 1970s and 1980s.

A public inquiry described the scale of the scandal as "horrifying", and accused doctors, the government and NHS of repeatedly failing patients.

Who was given infected blood and how many died?

Two main groups of NHS patients were affected by what has been called the biggest treatment disaster in the history of the NHS.

Firstly, haemophiliacs - and those with similar disorders - who have a rare genetic condition which means their blood does not clot properly.

People with haemophilia A have a shortage of a clotting agent called Factor VIII, while people with haemophilia B do not have enough Factor IX.

In the 1970s, a new treatment using donated human blood plasma was developed to replace these clotting agents.

But whole batches were contaminated with deadly viruses.

After being given the infected treatments, about 1,250 people in the UK with bleeding disorders developed both HIV and hepatitis C, including 380 children.

About two-thirds later died of Aids-related illnesses. Some unintentionally gave HIV to their partners.

Another 2,400 to 5,000 people developed hepatitis C on its own, which can cause cirrhosis and liver cancer.

It is difficult to know the exact number of people infected with hepatitis C, partly because it can take decades for symptoms to appear.

A second group of patients were given contaminated blood transfusions after childbirth, surgery or other medical treatment between 1970 and 1991.

The inquiry estimates between 80 and 100 of these people were infected with HIV, and about 27,000 with hepatitis C.

In total, it is thought about 2,900 people have died.

What did the infected blood inquiry say?

Announcing its findings in May 2024, the inquiry said victims had been failed "not once, but repeatedly", and that the risk of viral infections in blood products had been known since 1948.

Inquiry chairman Sir Brian Langstaff said there had been a lack of openness from the authorities and elements of "downright deception", including the destruction of documents.

He said half-truths were also told, so people did not know about the risk of their treatment, the availability of alternatives, or even whether they were infected.

"This disaster was not an accident," said Sir Brian. "The infections happened because those in authority - doctors, the blood services and successive governments - did not put patient safety first."

The report said:

too little was done to stop importing blood products from abroad, which used blood from high-risk donors such as prisoners and drug addicts

in the UK, blood donations were accepted from high-risk groups such as prisoners until 1986

blood products were not heat-treated to eliminate HIV until the end of 1985, although the risks were known in 1982

there was too little testing to reduce the risk of hepatitis, from the 1970s onwards

How does the compensation scheme work, and how much compensation will infected blood victims get?

Chancellor Rachel Reeves announced the £11.8bn total compensation figure during the Budget on 30 October.

The government had previously said that the first compensation payments would be made to victims before the end of 2024.

Family members and loved ones of those infected will also be entitled to compensation from 2025.

Payments will be exempt from tax, and will not affect benefits.

The final amounts for individuals are being assessed against five criteria: harm caused, social impact from stigma and isolation, impact on autonomy and private life, care costs and financial loss.

Outlining the compensation scheme after the inquiry reported in May 2024, the then-Conservative government suggested how much people might receive:

a person infected with HIV could expect to get compensation of between £2.2m and £2.6m

those with a chronic hepatitis C infection, defined as lasting more than six months, could expect to receive between £665,000 and £810,000

the partner of someone infected with HIV who is still alive today could expect to receive about £110,000, while a child could get £55,000

Annual payments will be available for relatives who had been financially dependent on the loved one who died.

In cases where people who would be entitled to compensation have themselves died, the money will go to their estate.

Have any compensation payments already been made?

In late 2022, following advice from the inquiry, the Conservative government made interim payments of £100,000 each to about 4,000 surviving victims and bereaved partners.

In June 2024, a second interim payment of £210,000 was paid to those infected.

In October 2024 the government said more relatives of those who died could also apply for £100,000 interim payments if the money had not already been claimed.

How did the infected blood scandal happen?

In the 1970s, the UK was struggling to meet the demand for blood-clotting treatments, so imported supplies from the US.

But much of the blood was bought from high-risk donors such as prison inmates and drug-users.

Factor VIII was made by pooling plasma from tens of thousands of donors.

If just one was carrying a virus, the entire batch could be contaminated.

UK blood donations were not routinely screened for hepatitis C until 1991, 18 months after the virus was first identified.

When did authorities know about infected blood?

By the mid-1970s, there were repeated warnings that imported US Factor VIII carried a greater risk of infection.

However, attempts to make the UK more self-sufficient in blood products failed, so the NHS continued using foreign supplies.

Campaigners say haemophiliacs could have been offered an alternative treatment called Cryoprecipitate. This was much harder to administer, but was made from the blood plasma of a single donor, lowering the infection risk.

BBC News has also uncovered evidence children were infected with hepatitis C and HIV after being placed on clinical trials of new treatments - often, without their family's consent.

As late as November 1983, the government insisted there was no "conclusive proof" that HIV could be transmitted in blood, a line robustly defended by former health minister Ken Clarke when he appeared before the inquiry.

What happened in other countries affected by infected blood?

Many other countries were affected, although some - including Finland - used older treatments until much later rather than switch to Factor VIII, which minimised HIV infections.

Delivering the findings of the inquiry, Sir Brian criticised UK government claims in the 1990s that screening for hepatitis C began as soon as the technology was available.

He said that 23 other countries - including Japan, Finland and Spain - introduced the screening before the UK.

In the US, companies that supplied infected products have paid out millions in out-of-court settlements.

Politicians and drug companies have been convicted of negligence in countries including France and Japan.

In his evidence to the inquiry, former health secretary Andy Burnham suggested there may be grounds for charges of corporate manslaughter in the UK.

Living With Hemophilia: Expert Insights On Management And Treatment

In an exclusive conversation with Deccan Chronicle, Dr. G Vikram Kumar sheds light on the complexities of hemophilia, its impact on patients' lives, and the recent breakthroughs in the treatment and management of this rare blood disorder.

Can you explain the basics of hemophilia, its types (A and B), and how it affects the body's ability to clot blood?

Hemophilia is a rare, inherited blood disorder that causes one's blood to clot less, which results in an increased risk of bleeding or bruising. Hemophilia happens because one's body doesn't make enough protein (clotting factors) to help blood form clots. Clotting factors are proteins in one's blood. They work with platelets to form blood clots that control bleeding. Low clotting factor levels increase bleeding risk. There are several types of Hemophilia. Hemophilia may be severe, moderate or mild based on the amount of clotting factor in your blood. Conventionally, the healthcare providers managed this condition by replacing the missing clotting factor (Replacement therapy/Prophylaxis). However, now with the non-factor prophylactic treatment made available, this provides superior and durable bleed protection than conventional therapies.

There are three types of hemophilia:

• Hemophilia A: This is the most common type of hemophilia. It happens when you don't have enough clotting factor 8 (factor VIII). The CDC estimates about 10 in 100,000 people have hemophilia A.

• Hemophilia B: Hemophilia B happens when you don't have enough clotting factor 9 (factor IX.) The CDC estimates about 3 in 100,000 people in the U.S. Have hemophilia B.

• Hemophilia C: Hemophilia C is also known as factor 11 (factor XI) deficiency. This hemophilia type is very rare, affecting 1 in 100,000 people.

What are the common symptoms and complications associated with hemophilia?

The most significant symptom is unusual or excessive bleeding or bruising. People with hemophilia may develop large bruises after minor injuries. This is a sign of bleeding under their skin. They may bleed for an unusually long time, whether that's bleeding after surgery, bleeding after dental treatment or simply bleeding from a cut finger. They may start bleeding for no apparent reason, such as sudden bloody noses. How much bruising or bleeding people have depends on whether they have severe, moderate or mild hemophilia: People with severe hemophilia often have spontaneous bleeding or bleeding for no apparent reason. People with moderate hemophilia who have serious injuries may bleed for an unusually long time. People with mild hemophilia may have unusual bleeding, but only after major surgery or injury. Other symptoms may include:

• Joint pain from internal bleeding: Joints in your ankles, knees, hips, and shoulders may ache, swell, or feel hot to the touch.

• Bleeding in the brain; People with severe hemophilia very rarely develop life-threatening bleeding in their brains. Brain bleeds may cause persistent headaches, double vision or make you feel very sleepy.

What are the current treatment options available for hemophilia patients in India, and how accessible are they?

There are two main modes of replacement therapy for hemophilia patients: either to stop bleeding (on-demand) or regular infusions of clotting factor to prevent bleeds (prophylaxis). Current treatment options include:

• Plasma-derived clotting factors

• Recombinant Factor Concentrates

• Extended Half-life Factor Products

• Non-factor therapy: Emicizumab (only approved drug in India)

Unlike other replacement therapies which require infusion via IV route up to 2-3 weeks, non-factor therapies offer a convenient subcutaneous form of treatment with a maintenance dosing frequency of once a month.

How does prophylactic treatment differ from on-demand treatment for hemophilia, and what are the benefits of prophylactic treatment?

All forms of prophylaxis (with Clotting Factor Concentrates or prophylaxis with non-factor replacement agents,e.G. Emicizumab) provide superior benefits over episodic/On demand therapy. Conventional prophylaxis, initiated early in life, has been associated with over 90% reduction in joint bleeding rates, annualized joint bleeding rates (AJBRs) below 3 per year, and a significant reduction in joint deterioration and degenerative joint disease.

• Prophylaxis also provides protection from other types of hemorrhages in hemophilia, including preventing or substantially reducing the risk of intracranial hemorrhage.

• Longer-term benefits include reduction of chronic musculoskeletal pain, functional limitations, and disability, need for orthopedic surgery, hospitalization, emergency room visits, and reduced length of hospital stays; all of this leads to greater participation (i.E., regular attendance) in educational, recreational, and professional activities, with improved quality of life.

• Because of these benefits, the World Health Organization (WHO), the World Federation of Hemophilia (WFH), and many national and international hemophilia organizations have endorsed early prophylaxis as the standard of care for children with a severe phenotype hemophilia and recommend that prophylaxis be continued lifelong.

Additionally, adults with severe phenotype hemophilia (if not already on prophylaxis) should initiate prophylaxis as well.

People with severe hemophilia in developing countries often don't survive till adulthood. Can you elaborate on the challenges they face?

• Lack of awareness of disease among healthcare workers and patients.

• Lack of diagnostic facilities

• Lack of continuous supply of clotting factor concentrates

• Lack of uniform protocols for the management of hemophilia across the country

How do limited access to healthcare facilities, diagnosis, and treatment impact hemophilia patients in India?

• Due to lack of access there will be a delay in the diagnosis of new cases

• Existing cases of hemophilia if they suffer any new bleed they have to travel long distances to receive factor concentrate. This is very important especially when they get life-threatening bleeds like an intracranial bleed

• Delay in diagnosis of hemophilia patients with inhibitors

Could you discuss a case study of a patient from Hyderabad who benefited from prophylactic treatment? We had 17-year-old twins who were suffering from hemophilia A. I saw them for the first time in March of 2021 march. At that time their mother used to bring both of them from a distance of 80km to Hyderabad. Most of the time they are not used to walking due to bleeding in the psoas muscle or bleeding in knee joints and used to have a lot of pain. They were depressed and not used to attending college regularly. It's not only the patients, the entire family used to suffer.

We have screened them for inhibitors and one of them was positive for inhibitors. We have started one child on factor 8 prophylaxis and another on emicizumab prophylaxis.

How has this patient's quality of life improved since starting prophylactic treatment?

Both of them are not having any spontaneous bleeding. Now they are attending college regularly. They come to take factors without their parents' help now. They are doing regular physiotherapy and have a better quality of life.

Are there any recent advancements or breakthroughs in hemophilia treatment that you're excited about?

Challenges with existing treatments are they have to be given intravenous route, more frequent administration, and risk of inhibitor development.

Newer therapies like extended half-life factors can be given less frequently

Drugs like Emicizumab can be given subcutaneous route, once a month and do not affect inhibitor formation

More exciting therapies like gene therapy which offer cures are still under clinical trials

How does hemophilia impact mental health and emotional well-being?

Due to recurrent spontaneous bleeds many patients if not treated properly develop target joints and joint deformities. This will eventually lead to disability which causes school or work absenteeism and lead to depression and poor quality of life

Can you discuss the importance of early diagnosis and treatment in managing hemophilia?

Early diagnosis and treatment of hemophilia is important because it can:

• Prevent tissue damage: Treating bleeding with factor replacement therapy as soon as possible can stop bleeding before tissue is damaged.

• Reduce the need for factor concentrates: Early treatment can reduce the amount of factor concentrates needed and help patients recover more quickly.

• Prevent hemophilic arthropathy: Early treatment with clotting factor concentrates can prevent hemophilic arthropathy.

• Improve long-term prognosis: Early detection, follow-up, and treatment can improve patients' long-term prognosis.

• Reduce mortality: Prompt diagnosis and treatment can reduce mortality.

• Prevent neurological sequelae: Prompt diagnosis and treatment can prevent neurological sequelae.

How do physical therapy and rehabilitation fit into the overall treatment plan for hemophilia patients?

Physical therapy is essential for reducing disability and improving the quality of life. Individualized rehabilitation programs could have a positive impact on the management of pain, joint health, and disability improvement. Joint mobilization and muscle stretching techniques have been reported as effective methods for improving joint health, range of motion, and joint pain.

Are there any notable differences in hemophilia management between pediatric and adult patients?

The goal of the treatment of a child with hemophilia is to enable the patient and their families to manage the illness as independently as possible and therefore lead more normal, healthy lives. It is important to provide primary prophylaxis to children to avoid target joints and subsequent disabilities.

For adults with hemophilia, it is important to reduce bleeding and severity of bleeding episodes. This can help prevent permanent joint damage and even death. Improving quality of life and life expectancy for people with hemophilia.

Despite different goals of therapy, the treatment modalities are common across age groups.

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