Disease of the Month: Hemophilia

Shots:

To create a wholesome environment for the current and the future generation, it’s totally up to life science companies and decision-makers to embrace and integrate every prospect of the underlying disease conditions and address those issues to find cures
To continue the series for disease of the month, PharmaShots brings this month a summary of the disease Hemophilia, a rare, genetic disorder that slows down the blood clotting process
17^th April is observed as World Hemophilia Day to raise awareness for hemophilia and other bleeding disorders.

Introduction:¹

Hemophilia is a rare, genetic disorder that slows down the blood clotting process, results in an increased risk of bleeding after an injury or surgery. It is more prominent in males as compared to females

It occurs when a clotting factor is missing or levels of the clotting factor are low

The three types of hemophilia are:

Hemophilia A (80%),
Hemophilia B (20%) and
Hemophilia C (<1% of cases)

Hemophilia A (Classic Hemophilia/Factor VIII Deficiency):

It caused by missing/ defective/ low level/ low expression of factor VIII (F8 gene mutation), Although it is passed down from parents to children. It affects ~10 in 100,000 people. Hemophilia A is four times as common as hemophilia B.

Hemophilia B (Christmas Disease/Factor IX deficiency):

It caused by missing/ defective/ low level / low expression of factor IX gene (F9 gene mutation). It affects ~3 in 100,000 people in the US

Hemophilia C (Rosenthal Syndrome):

It caused by missing/defective/low level/ low expression of factor XI (F11 gene mutation). Most commonly found in the Ashkenazi Jewish population. This hemophilia type is very rare, affecting 1 in 100,000 people.

Causes:

The most commonly type is Hemophilia inheritance that passed from mother to son through faulty gene located on mother’s X chromosome. Also, it could be congenital known as Congenital hemophilia. In some people hemophilia develop without any family history of the disorder known as acquired hemophilia.

Symptoms:¹

Prolonged oozing after injuries, tooth extractions or surgery
Hematoma
Bruising
Bleeding into the joints, mouth and gums
Bleeding of the mouth and gums, and bleeding that is hard to stop after losing a tooth.
Bleeding after circumcision
Bleeding after having shots, such as vaccinations.
Bleeding in the head of an infant after a difficult delivery.
Blood in the urine or stool
Nosebleeds without a known cause

Diagnosis:²

Prothrombin time (PT) test, a clotting factor test is performed to check the blood clotting factor in the body
Activated partial thromboplastin time test, a blood test to time blood clot formation.
Specific clotting factor test, a blood test that show specific clotting factor levels (such as factor 8 and factor 9)
Genetic testing for people with a family history of hemophilia, might be used to identify carriers to make informed decisions about becoming pregnant

Epidemiology:³

According to the US CDC, hemophilia A occurs in ~1 in 5,617 and hemophilia B is ~1 in 25,000-30,000 male births. In Aug 2022, there were ~33,000 people with hemophilia in the US.

Market Size:⁴ The global hemophilia market size accounted for $12.2B in 2021 and is projected to increase at $22.2B by 2030 at a CAGR of 6.9%

Treatment:⁵

The main treatment for severe hemophilia is boosting/ replacing missing clotting factor but some people who went through replacement therapies develop antibodies, called inhibitors, which attack the clotting factors that control bleeding. To overcome this, a technique called immune tolerance induction (ITI) is used in which clotting factors given on a daily basis to bring down inhibitor levels
In some forms of mild hemophilia Desmopressin hormone can inject slowly into a vein or used as a nasal spray to stimulate the body to release more clotting factor
Clot-preserving medications/anti-fibrinolytics medications help prevent clots from breaking down
Avoid blood-thinning medications like heparin, warfarin, clopidogrel etc.
Fibrin sealants can be applied directly to wound sites to promote clotting and healing. Fibrin sealants are especially useful for dental work.

Key Players in the Market:

Hemgenix (etranacogene dezaparvovec)⁶is a one-time gene therapy for the treatment of adults for hemophilia B, who is currently use Factor IX prophylaxis therapy, or have current or historical life-threatening bleeding, repeated, serious spontaneous bleeding episode. It was developed by UniQure and marketed by CSL Behring through a 2021 licensing agreement

Other key leaders with approved molecules in the market are: Novo Nordisk, Sanofi, Roche, Bayer etc.

Clinical Trial Analysis:⁷

As of Mar 23, 2023, total 69 clinical trials are ongoing worldwide for hemophilia. Some of the key molecules involved in the trials are: Concizumab and Mim8 (Novo Nordisk), Emicizumab (Hoffmann-La Roche) etc.

Various gene therapy researches are ongoing that may offer a cure for hemophilia in the future. Also, research is ongoing on Stem cells from bone marrow to provide therapeutic aid for hemophilia A patients

Based on G10 geography distribution, the interventional clinical trials are classified in the below mentioned graph in two groups based on its status i.e., active (recruiting, active, not recruiting, not yet recruiting and enrolling by invitation) and inactive (withdrawn, suspended terminated and trials with unknow status). The interpretation showed that highest no. of trials being conducted in the USA and the least number of trials are reported in India and Japan (as represented in the graph)