Science Policy Around the Web December 10th, 2019

By Kellsye Fabian MS, PhD

Image by allinonemovie from Pixabay 

Two New Drugs Help Relieve Sickle-Cell Disease. But Who Will Pay?

The FDA recently approved two new treatments for sickle-cell disease — Adakveo and Oxbryta. Sickle-cell disease is caused by a gene mutation that results in abnormal hemoglobin and sickle-shaped red blood cells. These cells clump together, restricting the flow in blood vessels and limiting oxygen delivery to the body’s tissues. This leads to severe pain and organ damage. Adakveo, made by Novartis, can prevent occurrence of bouts of severe pain caused by misshapen blood cells getting stuck in blood vessels. Oxbryta, made by Global Blood Therapeutics, can prevent disease-induced anemia that can result in permanent damage to the brain and other organs. For a disease that has been historically overlooked, the availability of these new cutting-edge medicines may represent new hope for people with sickle-cell disease. However, the new drugs might not be accessible to all ~100,000 Americans with the disease. Each treatment must be taken for life and is priced at $100,000 a year, which is double the median family income in the US.

Novartis and Global Blood Therapeutics have been in negotiation with insurance providers about covering the new drugs. Both companies are optimistic that most insurers will pay for the new treatments. The companies argue that without these drugs, the management of sickle-cell disease is expensive. Treating sickle-cell disease complications such as pain, stroke, and organ damage costs about $10,000 a year for children and about $30,000 for adults. Not included in that amount is the economic burden on adults who cannot work due to debilitating disabilities associated with sickle-cell disease and on family members who often wind up as caregivers.

Despite this, some experts and patient advocacy groups question the drug makers’ justification for the treatments’ hefty price tags. Actual development costs and taxpayer support must be considered when setting the price for these treatments. 

More affordable options are available for sickle-cell disease patients. Hydroxyurea, which was approved in 1998 and can reduce the frequency of pain crises and stroke, costs about $1,000 a year. While some patients on public insurance programs have $0 co-pays for Hydroxyurea, only 30% of sickle-cell patients take it. Therefore, insurers may possibly require sickle-cell disease patients to be treated with hydroxyurea before moving on to the more expensive Adakveo or Oxbryta.

Medicaid covers about 50% of sickle-cell disease patients while Medicare covers another 15%. It remains unclear how these programs can afford to pay for all who might need the new drugs. 

(Gina Kolota, New York Times) 

FDA warns Liveyon about selling unapproved stem-cell products that pose a risk to consumers

The FDA has issued a warning to Liveyon Labs and Liveyon LLC of Yorba Linda, California for making and selling unapproved umbilical cord blood products. The agency also issued a warning for significant deviations from safety practices that create serious risks for patients that receive the stem cell therapy.

In 2018, Liveyon LLC distributed contaminated non-FDA-approved umbilical cord blood products processed by the San Diego-based company, Genetech, Inc. The products were linked to the hospitalization of twelve patients who received the injections or infusions. Liveyon conducted a voluntary recall and began making its own products called Pure and Pure Pro through Liveyon Labs. These products are marketed mainly as a treatment for patients with back, knee, and other joint problems. 

An FDA inspection conducted in May revealed that Liveyon Labs and Liveyon LLC were manufacturing and distributing products that are considered drugs although they did not have the approval to do so. An approved biologics license application is needed to lawfully market a drug and an approved investigational new drug application (IND) is required for a drug to be used in humans during the development stage. No such licenses or INDs exist for Pure and Pure Pro. The inspection also documented that the companies did not meet safety standards, including failing to screen donors’ relevant medical records for communicable disease, inadequate aseptic practices to prevent contamination, and deficient environmental monitoring, such as failing to establish a system for cleaning and disinfection the processing room and equipment. According to the FDA, Liveyon took some corrective actions after the inspection. However, Liveyon has yet to provide “proof of updated policies and procedures” and it did not address its lack of required approvals. 

The FDA requested a response from the companies within 15 working days that details how the issues will be corrected. Failure to correct the problems could lead to seizure, injunction or prosecution. Liveyon said it would cooperate with the FDA. 

(Laurie McGinley, The Washington Post) 

Sickle Cell Disease in Sub-Saharan Africa: Using Science Diplomacy to Promote Global Health

By: Steven Brooks, PhD

         Science diplomacy is an important conduit through which nations can cooperate with each other to help address issues of common concern. Establishing international collaborations based on scientific research and resource sharing can be a valuable tool to promote advances in global health and to help foster research communities in developing nations. In 2001, Nelson Mandela proposed a model for building and advancing a network of institutions investing in Science, Engineering, and Technology (SET) across sub-Saharan Africa (SSA) to enhance economic diversification, promote job growth, and improve living conditions for peoples across the region. Since then, significant strides have been made by many international organizations, including the World Health Organization, World Bank, and United Nations, to invest in SET institutions and researchers across SSA. Much work is still needed, however, to address the significant global health disparities affecting SSA. According to the United Nations Development Programme, life expectancy in SSA is on average only 46 years. Among the largest contributory factors to this gap is HIV/AIDS, but non-communicable diseases and genetic conditions such as Sickle Cell Disease (SCD) contribute as well. SCD in particular offers a stark geographic contrast in disease outcome: in the United States, childhood mortality (up to age 18) from SCD is below 10%, while in SSA the early childhood mortality rate is 50-90% by age 5. This drastic difference in childhood mortality from SCD raises an important question- why is the difference in mortality rates so large, and what can be done to eliminate it?

SCD represents a significant public health success in the United States. From the early 1970s, average life expectancy of people with SCD has substantially increased from 14 years of age to over 40 years, and childhood mortality rates have continued to decline. These vast improvements in SCD mortality in the US are attributable to improvements in screening and early diagnosis, as well as surveillance for early childhood infections and prophylactic treatments.  Availability of therapies like hydroxyurea and access to blood transfusions have also contributed to reducing childhood mortality, while several currently ongoing clinical trials in the US are testing the use of bone marrow transplantation as a curative procedure for patients with severe complications of SCD. While the best practices for diagnosing and treating SCD are well-established in developed nations, lack of global implementation has meant that these advances in treatment have had very limited effect on reducing mortality and improving quality of life in developing nations. More than 85% of all new SCD cases occur in SSA, with over 240,000 infants with SCD born in SSA annually (compared to less than 2,000 in the US). Many nations in SSA do not have the resources or personnel to implement protocols for screening and diagnosis, and many children are born outside of hospitals. As a result, most children born with SCD in SSA will go undiagnosed, and therefore untreated, leading to devastatingly high rates of early childhood mortality for children with SCD.

The disparity in health outcomes between children born with SCD in developed nations and developing nations in SSA should be addressed through science diplomacy. An opportunity exists for diplomatic cooperation between scientists and health officials from the US and their counterparts in SSA to build infrastructure and train researchers and healthcare professionals to diagnose, treat, and innovate new solutions for SCD. The crucial first steps towards improving outcomes in SCD – parental and newborn screening, early childhood nutrition standards, parental and community education, and anti-bacterial and anti-viral vaccinations and prophylaxis – are achievable through diplomatic efforts and collaboration with governmental health agencies across SSA. Proof of this concept has been demonstrated in Bamako, Mali, with the success of the CRLD (The Center for Sickle Cell Disease Research and Control), a SCD-specific treatment and research center that reflects an effort of the government of Mali, with funding and medical resources provided by the Foundation Pierre Fabre. The CRLD utilizes modern diagnostic techniques to screen for SCD. It also provides immunizations, hospitalizations, and access to preventive medicine, and provides education and outreach to patients and to the larger community. Historically, the infant mortality rate from SCD in Mali was estimated to be 50% by age 5. Since the opening of the CRLD in 2005, only 81 of the over 6,000 patients enrolled at CRLD have died, a mortality rate for this cohort that is comparable to rates in the US and UK. The CRLD also has modern laboratories that conduct research, with over 20 academic papers published from the CRLD so far. The ongoing success of the CRLD is proof that investment in, and collaboration with, governments and medical professionals in Africa can lead to equitable health outcomes in SCD. Similar investments by the US government and the National Institutes of Health (NIH), possibly through intramural research programs, and in cooperation with health-focused private foundations, could lead to similar success stories in communities across SSA.

The NIH supports and facilitates collaborations in global health research through the NIH Fogarty International Center (FIC), which currently sponsors projects in 20 countries across SSA. NIH has also invested intramural resources into collaborations in SSA to combat Malaria. The National Institute of Allergy and Infectious Diseases (NIAID) trains and sponsors investigators to independently conduct research in Mali (NIAID’s Mali ICER (International Centers of Excellence in Research)). Despite its significant history of investment in SSA, the NIH offers almost no international support for research related to SCD. The NIH FIC only currently funds one project related to SCD, preventing pediatric stroke in Nigerian Children. The Division of Intramural Research at the NIH is currently home to robust basic science and clinical-translational research on SCD. Intramural researchers can and should collaborate with clinicians and scientists from SSA who will lead the effort to combat SCD in their home nations. More broadly, the NIH could spearhead an initiative to bring together stakeholders from the US government, health ministries from nations in SSA, and private foundations that support efforts to reduce or eradicate global disease, to begin establishing a network of laboratory and clinical facilities for testing and treatment, as well as to train clinicians and researchers from SSA in diagnostic and research techniques specific to SCD, and to design and disseminate educational resources for increasing communal knowledge regarding SCD across SSA.

In addition to significantly improving SCD mortality and health outcomes in SSA, these efforts of science diplomacy will have substantial benefits in the US as well. The US is home to a sizeable, and growing population of people living with SCD. As life expectancy continues to increase, new challenges will arise for effectively treating serious complications associated with SCD, such as renal disease, stroke, cardiovascular disease, heart failure, cardiomyopathy, and pulmonary hypertension. By collaborating with researchers and healthcare leaders studying large populations of people with SCD in SSA, the NIH will foster innovation and generate new insights about SCD that are uniquely informed by the data and perspectives of African scientists and populations. The NIH and the US government can establish a mutually beneficial program of treatment, education, and research that will enable developing nations to treat their patients with the same methods available in the US. Investing in 21^st century methods of diagnosis and treatment, as well as contributing funding, training, and infrastructure to clinicians and researchers in SSA, can strengthen diplomatic relationships between governmental leaders and scientists alike and lead to lasting collaborations that strengthens research and innovation into new treatments for SCD.

Have an interesting science policy link?  Share it in the comments!