Govt considers low-dose emicizumab for haemophilia, trial finds it more effective than existing treatment

‘Miracle drug’ can cost Rs 13 lakh for haemophilia A patient annually, but reduced dose found efficacious & cost-effective in small trial. Larger trial is under way.

Roche’s emicizumab is the top therapy for a common form of haemophilia called ‘haemophilia A’ | Pixabay

New Delhi: The Centre is evaluating whether low-dose emicizumab, a drug that has revolutionised haemophilia management, can be offered in place of the current treatment provided for the condition in government hospitals, following a recommendation by the Indian Council of Medical Research (ICMR).

State governments offer haemophilia management drugs free of cost to patients with assistance from the central government under the National Health Mission.

A few states in the country have started providing emicizumab—the therapy for a common form of haemophilia called ‘haemophilia A’ by Swiss pharma giant Roche, available under the brand name Hemlibra—but most others do not.

Even for the states trying to offer the novel therapy, sustaining the supplies due to its high cost—the drug can cost nearly Rs 13 lakh for an average hemophilia A patient annually—remains a challenge.

Haemophilia is a genetic bleeding disorder that prevents blood from clotting properly due to a deficiency in proteins responsible for clotting. Patients with this condition experience prolonged bleeding after injuries, easy bruising, and have increased risk of internal bleeding that can be life-threatening.

Haemophilia A is caused by a lack of or low level of factor VIII, a crucial protein required for blood clotting.

While high dose primary FVIII prophylaxis (25-40 international units or IU/kg every 48 hours) still remains the standard of care for persons with haemophilia A in countries with adequate resources, in countries like India only low-dose FVIII (10-15 IU/kg twice a week) is used owing to its cost-effectiveness.

“Given the dramatic benefit emicizumab offers in terms of reducing bleeding episodes, it has emerged as a therapy of choice for haemophilia A,” Dr Manisha R. Madkaikar, director of Mumbai-based ICMR-National Institute of Immunohaematology (ICMR-NIIH), told ThePrint.

But due to its high costs, most patients have not been able to access it at government hospitals, she said.

Now, Health Technology Assessment (HTA) under the department of health research in the Union health ministry, responsible for generating evidence related to clinical, cost effectiveness and safety of medicines, devices and health programmes, is assessing whether reduced emicizumab can replace the low dose primary FVIII prophylaxis which is offered to patients owing to cost reasons.

“This is after our scientific research showed that half of the standard dose of emicizumab is as effective in managing haemophilia as its standard dose, and far more efficacious and cost-effective than the current standard of care offered,” Madkaikar said.

According to sources in the health ministry, a larger trial to validate the finding is under way.

Haemophilia and its changing treatment landscape 

Health experts explain that when somebody bleeds, their body takes steps to stop the bleeding and 13 different proteins called clotting factors work together to form a blood clot.

Haemophilia, passed to a child from their parents, prevents blood from clotting. People with haemophilia have a clotting factor that is missing or reduced. As they cannot form blood clots, this makes bleeding last longer than it should.

It is estimated that India has nearly 1,40,000 haemophilia patients, of whom only nearly about 27,000 are registered. The majority of the patients with the condition have haemophilia A, the commonest form of the disease.

In the case of haemophilia A, when there is low level of blood-clotting protein, Factor VIII (FVIII) and its level measured in percentage terms determines the severity of the condition.

Severe haemophilia usually becomes apparent in the first years of life–often when the child starts to move about independently. Haemorrhages often occur in the joints, especially the weight bearing joints such as knees and ankles.

Such joint bleeding can cause severe pain and often permanent damage and disability if not treated properly. Other mild, moderate or even life-or-limb threatening bleeds can occur in the muscles, soft tissues, gastrointestinal tract or even the brain.

In addition, trauma, major surgery, tooth extractions or other minor surgical interventions require medical treatment to manage the associated bleeding.

“Approximately 30-50 percent of haemophilia patients have severe disease and can require treatment for bleeding several times per month,” Dr Varun Kaul, paediatrician and researcher in thalassemia and haemophilia at Baba Farid University of Health Sciences in Punjab, told ThePrint.

Traditionally, the primary treatment for haemophilia involved the replacement of the missing clotting factor and most often, this therapy was used to be given after a bleeding episode.

However, prophylaxis or preventive treatment is now considered the gold standard for haemophilia management and this can involve either replacing the clotting factors periodically or using non-factor therapies such as emicizumab, Dr Kaul added, calling it a “miracle drug”.

Emicizumab was launched in the country in 2019 and has emerged as the medication of choice for most physicians treating the condition.

A bispecific antibody designed to target two antigens, it is administered subcutaneously and offers distinct advantages by reducing bleeding risk, lowering inhibitor development, and improving treatment adherence and long-term efficacy.

“The drug works by mimicking FVIII and considerably brings down bleeding episodes in its users and remarkably improves their quality of life,” Kaul said, adding that considering the cost-effectiveness with low-dose, it “makes sense to consider the option”.

Why low-dose emicizumab?

According to ICMR researchers, while low dose FVIII, which the government programme offers, reduces annual bleeding rate, long-term joint outcomes remain poor.

Also, among those with haemophilia A, only 9 percent of those under 18 years and 4 percent of those over 18 years actually receive FVIII prophylaxis for a myriad of reasons, some of which include inadequate or unsustainable supply, issues of access, adherence, awareness, and lack of laboratory monitoring, they said.

The researchers noted that emicizumab is the first non-factor bispecific monoclonal antibody approved for use in haemophilia A patients in India, and with the recommended dose, gives zero treated bleeds and helps in the resolution of target joint bleeds in the majority of patients.

However, its cost precludes its use in countries like India.

It was for this reason that an audit of low-dose off-label use of the drug was planned with the aim of assessing its efficacy and safety compared with that of low-dose FVIII prophylaxis.

The study involved 23 patients and was published last year in Journal of Thrombosis and Haemostasis. It showed that a standard dose of emicizumab cost Rs 13 lakh annually per patient, but on low dose, which resulted in the same benefits to the patients, its cost came down to under Rs 5.1 lakh.

In comparison, low dose FVIII prophylaxis costs Rs 5.37 lakh per patient.

“Low-dose emicizumab offers a cost-effective treatment option and can improve access in developing countries,” the paper notes, adding that the findings need to be confirmed in a larger and better-controlled study.

“A decision to provide low-dose emicizumab for managing haemophilia may result in huge savings to the government exchequer in the long run,” Madkaikar, who was among the scientists who conducted the research, said.

Kaul, who is not associated with the research, agreed. “At a programmatic level, it may be more pragmatic to let all patients who need the drug access it and get benefitted,” Kaul also said.

(Edited by Nida Fatima Siddiqui)