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Discovery of Genetic Link to PML Honored by Largest MS Conference in the World

Life-saving preventative screening now available to patients considering PML-inducing drugs; Discovery shared honors for Best of MSMilan2023

NEWPORT BEACH, Calif., Oct. 17, 2023 /PRNewswire/ -- The discovery of rare genomic variants leading to cases of drug-induced PML shared Best of MSMilan2023 honors for the latest and most breakthrough results at the 9th Joint ECTRIMS-ACTRIMS Meeting.

Two of the variants have a Positive Predictive Value of 100%, the strongest possible indication they are causative.

Co-hosted by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), the annual conference is the largest multiple sclerosis (MS) meeting in the world where 9,000 participants shared the latest advancements in MS research and treatment.

Progressive Multifocal Leukoencephalopathy (PML) is a rare but frequently fatal serious infection of the brain by the JC virus. While PML can occur in patients with a variety of conditions (e.g., HIV/AIDS, hematological malignancies, autoimmune disorders, and organ transplants), MS patients typically have an increased risk of PML due to drugs they take to treat their MS.

Lead co-author Dr. Eli Hatchwell was selected to give an oral presentation, where he demonstrated the genetic link to PML cases on drugs like natalizumab (Tysabri) and the biological significance of the genes where the mutations are located. Out of 1,500 abstracts presented, Dr. Hatchwell's was one of eight highlighted as Best of MSMilan2023 in its content area.

Preventative screening is expected to become a routine part of patient care, as previously recommended by leading neurologists Drs. Berger, Hartung, and Steinman. Additionally, patients have expressed their overwhelming support for variant testing. Recent surveys of several hundred current and former patients on the PML-linked drugs Tysabri, Ocrevus, Benlysta, and Mavenclad consistently show 90%+ are interested in being tested for the variants and that they and their doctors should be informed of its availability.

When Franklin Jordan, 58, a PML survivor who developed PML after taking Tysabri, learned about the availability of the genetic test, he said, "I would have taken the test in a minute. If I knew I was positive, I wouldn't have taken Tysabri." Tysabri is manufactured by Biogen Inc. and was originally withdrawn from the market in 2005. After emotional patient testimony, the drug was reintroduced with the FDA's highest Black Box Warning for PML in 2006 and it continues to be among the most effective disease modifying therapies for MS patients. In the last 10 years, Biogen has proactively added several mitigation measures, including blood testing, to lower PML risk for Tysabri patients but has not added this simple genetic screening to its repertoire.  

The four genomic variants predict who will develop PML better than BRCA testing predicts breast cancer, and if present they increase the risk of PML 10-fold. Two of the variants have a Positive Predictive Value (PPV) of 100%, the strongest possible indication that they are causative. Their population frequency is many orders of magnitude greater than the failure rate that triggered government safety regulators' recent decision to take steps to recall over 50 million airbag inflators this coming year.

Many MS medications currently carry a PML warning, including Tysabri, Ocrevus, and Rituxan, as well as Briumvi, Gilenya, Kesimpta, Mavenclad, Mayzent, Ponvory, and Tecfidera. However, medications widely prescribed for blood cancers and organ transplants, as well as autoimmune diseases like inflammatory bowel disease, lupus, and rheumatoid arthritis, also include PML warnings on their drug labels. Some of these drugs include Adcetris, Benlysta, Entyvio, Gazyva, Imbruvica and Jakafi. There are even drugs on the market experiencing an increase in reported PML cases, yet they do not carry a PML warning, such as Darzalex for multiple myeloma. 

Since 2011, drug-induced PML cases reported to the FDA have more than doubled. In the first half of 2023 alone there have been 335 cases and nearly 100 deaths in the FDA's adverse event reporting system (FAERS). As previously reported by the American Neurological Association in September 2023, nearly 100 drugs have been linked to PML in that database. 

To fill the immediate need for testing, the PML Foundation is currently offering a free test online. Simpler than a COVID swab, the at-home saliva test is processed in a CLIA-certified lab by PreventionGenetics, a leader in the field for almost 20 years. The free test is available at pmlrisktest.org.    

The original study was funded by Emerald Lake Safety LLC and Population Bio, Inc.

About Emerald Lake Safety
Emerald Lake Safety (ELS) conducts research into the mechanisms behind Serious Adverse Events associated with marketed pharmaceuticals. We conduct clinical and genomic research both on our own and in conjunction with leading academics and scientists from around the world. For more information visit www.emeraldlakesafety.com.

About Population Bio
Population Bio is a precision medicine company with a mission to make pharmaceuticals safer and more effective. By discovering disease-relevant genetic biomarkers, Population Bio helps develop targeted therapies and companion diagnostics faster and more cost effectively. Population Bio's patented technology platform is currently addressing complex neurological diseases such as Alzheimer's, Parkinson's, and Autism, as well as women's health conditions such as Endometriosis. For more information visit www.populationbio.com.

Press Contact:

Amy Losak
917-520-1207
losak@optonline.net

SOURCE Emerald Lake Safety LLC and Population Bio, Inc.