Hemophilia gene therapy: Where do we stand?

TAGS: Gene Therapy
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In hemophilia gene therapy, the gene introduced encodes for the clotting factor that the patient is lacking.

Hemophilia is a genetic disease that stems from the deficiency of a protein required for normal blood clotting – clotting factor VIII in hemophilia A or clotting factor IX in hemophilia B. As the level of factor VIII or IX in the blood usually stays the same throughout life, hemophilia is a lifelong disease. Hemophilia patients bleed excessively when injured, and those with more severe forms of the disease can even experience spontaneous bleeding around the joints or other areas that can be life-threatening.

Hemophilia is commonly treated using infusions to replace the missing clotting factor in the blood. These have been available since the late 1960s.

Gene therapy, a non-factor treatment currently in development, is starting to shift the treatment paradigm, as it addresses the root cause of the disease.

Hemophilia treatment advances were highlighted in the 11th Global Hemophilia Summit organised by Pfizer in September. The summit connected 916 healthcare professionals from 60 countries in a four-day-virtual programme. Gene therapy is a specialised treatment that inserts the corrected gene into the patient’s cells to replace the defective one or modulate the expression of a targeted gene to correct the disease. Significant progress is made in the field since discovering novel adeno-assisted virus (AAV) vectors that are small viruses used to deliver genetic material to the cells. This discovery has been promising as AAV vectors can do the job without damaging the cells or permanently altering the genome in an unwanted way.

In hemophilia gene therapy, the gene introduced encodes for the clotting factor that the patient is lacking. Following the treatment, it is expected that the patient would not need continued prophylaxis or factor replacement following trauma or before surgery.

Hemophilia gene therapy brings hope to many patients, as it is a one-time fix that is also cost-effective in the long run. The first patient dosed in the longest-running factor IX trial has now passed the 8-year mark with steady levels of factor expression.

Furthermore, there were 31 clinical trials for hemophilia in one of the latest ClinicalTrials.gov report, and the last phase clinical trials for factor VIII and IX are now underway.

The results from these clinical trials confirm that the safety and efficacy of gene therapy for hemophilia are persuasive. When licensed, gene therapy is initially limited to adults with severe hemophilia and will exclude those with inhibitors. Moreover, to check eligibility for gene therapies with viral vectors, it is crucial to run an immunity check against viral vectors, and patients with significant liver dysfunction, those who are positive for Hepatitis B (through surface antigen detection test) or positive for Hepatitis C infection (through RNA detection test) will not be eligible.

In conclusion, gene therapy remains a complicated area, which is highly demanding in terms of material and human resources. In Africa and the Middle East region, adequate funding and strategic partnerships are essential to provide a base to facilitate meaningful progress.

This year two knowledge-sharing sessions were conducted with the UAE MOHAP and SFDA together with Pfizer. Pfizer will continue to partner with UAE and Saudi Arabia’s scientific and regulatory authorities for novel initiatives, and continuous medical education and training in gene therapy. In these partnerships, there is a plan for providing centres to conduct five gene therapy clinical trials in the Middle East.

As companies will need to prepare for current and future manufacturing demand with time, personnel, and capacity to ensure new robust quality systems, treatment innovation will be accompanied by both opportunities and challenges. However, the future for hemophilia is exciting, and patients, physicians, healthcare leaders must leverage the coming wave of innovation.

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Mert Ceyhan

References available on request.

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