WFH launches several new safe treatment product initiatives

The HIV/AIDS epidemic in the 1980s was a shock that made citizens and governments throughout the world scrutinize blood-supply safety. Since then, the WFH has been a leader in blood-safety and treatment-access initiatives.

During the Tuesday afternoon session “Leading Global Surveillance and Collaboration: The WFH’s Role in Ensuring Safety and Supply of Treatment Products,” presenters discussed new WFH programs, including a comparative database of factor products, a collaborative genotyping project using 5,000 blood samples from people with hemophilia A and B and a Worldwide Bleeding Disorders Registry.

David Page, the first chairman of the WFH’s Blood Safety Committee, detailed the WFH’s stance on blood safety, including factor manufacturing.

“Today, many governments and blood establishments are doing their best to be more discriminatory” after the HIV/AIDS and hepatitis C crises, Page said. This includes instituting donor referrals for high-risk populations, such as men who have sex with men (MSM). WFH recognizes that MSM donor-referral policies are discriminatory, but leaves specific policies to individual countries, he said.

In terms of blood products, Page said the WFH lists safety steps for manufacturing factor concentrates: Use only healthy donors, screen each donation with antibody and nucleic acid tests for multiple viruses, institute a plasma hold to allow time for a concern to be reported, and institute purification steps and viral reduction/removal steps.

Based on new research over the last 15 years, the Blood Safety Committee has had a clear shift in focus from pathogen effects to immunogenicity, Page said.

Brian O’Mahony, current chair of the Blood Safety Committee, discussed the committee’s involvement in worldwide regulations. The WFH’s main goal is to ensure adequate supply and access to treatment.

O’Mahony said key initiatives the WFH is involved in include:

  • The World Health Organization’s (WHO) Essential Medicines List. More than 130 countries use this list to develop their essential medicines. The WFH has helped ensure that FVIII, FIX and desmopressin are on the list.
  • The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products. More than 1,200 therapies have orphan status in Europe. The WFH has successfully fought against orphan drug designation for factor concentrates, arguing that it could hinder the development, licensing and marketing of similar products for hemophilia.
  • Paid plasma bans by organisations like WHO and the Canadian government. WFH and seven other patient organisations formed a plasma-users commission in 2010, and in 2011, released a consensus statement that plasma products made from both non-remunerated and remunerated donations are currently essential to meet global health needs.

But despite these efforts, “The debate goes on—it’s endless fun,” O’Mahony said sarcastically. “The problem is that there are some people whose views haven’t changed since the tragic events of the 1980s.”

Mark Brooker, WFH, discussed regulatory questions members ask about products:

  • Label indications for pediatric use. Most products, particularly in Europe, are licensed for adults only, Brooker said. Members have concerns that this delays getting products on the market.
  • SIPPET study fallout. This study found that recombinant FVIII users were more likely than plasma users to develop an inhibitor. “This is tricky for us because we’ve been using those recombinant factors for years,” Brooker said. The WFH is very clear that not treating is the worst choice, he added, meaning it’s better to use recombinant factor than to not treat at all.
  • Products not approved by the EMA and Food and Drug Administration (FDA). EMA and FDA approvals are accepted by most countries. But some countries can require testing for non-FDA and EMA products, which can be frustrating for small manufacturers.


Brooker also announced the WFH’s new Online Registry of Clotting Factor Concentrates. This registry was originally created by the International Society on Thrombosis and Haemostasis, and transferred to the WFH in 2008.

The registry is now online at Brooker said it’s a comprehensive clearinghouse for product information and also allows users to compare products. In the next few months, the WFH is planning to add regulatory status for products, with future plans to include data for products in the pipeline.

Glenn Pierce, board member of Global Blood Therapeutics, closed the session with a look at product data gaps and exciting new initiatives being created through the WFH and private-public collaborations.

“We could be doing a much better job in the global hemophilia community to provide evidence to support bleeding-disorder products,” he said.

First of all, Pierce said there’s an efficacy-effectiveness gap in bleeding-disorder product trials. Specifically, patient populations tend to be more homogenous than they are in real life, and the studies tend to focus more on patient outcomes than other data. Pierce said providing more data will appeal to payers, who want head-to-head comparisons of products, utilization of healthcare resources, and final versus surrogate endpoints.

For instance, he said, previously untreated patient (PUP) studies on the risk of inhibitor development may look at the same small numbers of PUPs. But only about 750 PUPs are born in the U.S. and Europe each year, so “We’re dealing with a small, precious commodity,” Pierce said. “The question is should we use the PUPs for product analysis, or to determine how to prevent inhibitor development?” Pharma really has no impetus to do the latter, he said.

Trough levels are another issue, Pierce said. The concept of a trough level of 1 percent stems from historical product shortages and consistently high per-unit pricing. “But inadequate trough levels are the biggest single cause of morbidity and mortality in prophylactic treatment,” Pierce said. Troughs should be at 10 to 15 percent factor activity, which is the minimum required for a bleed-free existence.

The good news is that there are some products in development for low trough levels: Emicizumab, Fitusiran, AAV-FIX and AAV-FVIII. “This should be changing treatment paradigms as we go forward,” Pierce said.

He also discussed a new, collaborative genotyping project to collect 5,000 blood samples from people with hemophilia A and B. The goal is to create a research repository to look for risk factors for the complications of hemophilia. So far, 2,000 samples have been sent to the U.S. National Institutes of Health for full genome sequencing.

The repository will be open to researchers within the next six months. “We are very fortunate to have this number of samples to be able to answer a number of significant research questions,” Pierce said.

The WFH is also creating a Worldwide Bleeding Disorder Registry (WBDR). The pilot phase is underway with 31 hemophilia treatment centers, with completion scheduled for this December.

“High-quality observational data is being collected,” Pierce said. “This facilitates research by sharing data with the scientific community to address gaps in evidence to improve diagnosis and care, support advocacy initiatives and allow the scientific community to address unresolved clinical questions.”