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Grifols Betting on Free OTC Tests to Expand COPD Diagnoses, Treatment

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NEW YORK – To combat widespread underdiagnosis of a protein deficiency that can result in chronic obstructive pulmonary disease, Grifols is launching an over-the-counter version of its genetic test to screen for the deficiency.

The OTC test will be offered for free, the firm added, and with proper screening, such patients could benefit from treatments, including Grifols' own plasma-based AAT augmentation therapy.

Starting in the second quarter of 2023, Grifols will provide, without the need for a prescription, its US Food and Drug Administration 510(k)-cleared AlphaID test, a PCR-based test that uses at-home collected cheek swab samples and lab-based testing to identify 14 genetic variants in the serpin peptidase inhibitor class A member 1 (SERPINA1) gene that are linked with decreased protease inhibitor activity in a patient's blood and lungs.

Those mutations explain about 95 percent of cases of AAT deficiency, according to the 510(k) document for the OTC test. The agency noted, however, that the test results alone do not describe a person's overall risk of developing AAT deficiency, which should be considered along with other genetic and nongenetic factors.

The test will be available over the counter in the US only although the firm is considering offering it in Canada, which also allows direct-to-consumer sales of such tests.

The test, developed through Grifols' Progenika Biopharma subsidiary, is meant to help adult patients identify a cause of liver and lung disease, including COPD. By making the test free and available without a prescription, Grifols officials cited overwhelming underdiagnosis of the genetic condition by physicians who often dismiss breathing difficulties as the products of advanced age or lack of previous exercise, or who misdiagnose the symptoms as the products of asthma.

The AAT protein is produced in the liver and released into the bloodstream. In the lungs, it inactivates neutrophil elastase that originates in white blood cells, protecting lung tissue from damage by those enzymes. Deficiency of that protein can lead to early onset emphysema, chronic progressive fatigue, shortness of breath, chronic cough, and wheezing.

Antonio Martinez, president of Grifols Diagnostics, said the AAT deficiency is diagnosed in only about 10 percent of the patients who have the genetic condition.

"It takes several years until these patients are diagnosed, and that's a significant cost for the health system," he said. "If you arrive at the right diagnosis from the beginning, that patient will not suffer that long journey until he is correctly diagnosed, and it will mean savings for the health system because you are not wasting resources until the patient is diagnosed."

The firm's OTC test is the same as the prescription AlphaID test Grifols has been distributing globally since 2018. The firm launched the prescription test in the US in November 2019 for use by healthcare providers saying at the time that it would help patients understand their condition and make informed treatment decisions. That test was also free to patients.

The 510(k) documents state that any diagnostic or treatment decisions must be based on confirmatory prescription testing and/or other information a healthcare professional deems appropriate. Grifols' fingerstick AlphaID Confirm test is one such confirmatory test.

Grifols added that the company performed a user comprehension study with 525 participants ahead of the over-the-counter clearance as well as conducted additional studies to verify the adequacy of its test methods, laboratory analysis, and website for ordering tests.

Martinez said Grifols has already provided about 1 million of the prescription-based tests through doctors' offices and is now trying to increase demand through public education about the disease and the free OTC tests that could help identify who would benefit from the firm's treatment.

Grifols' Prolastin-C and Prolastin-C Liquid are two of at least five AAT augmentation therapies available in the US, including Takeda's Aralast NP and Glassia products and CSL Behring's Zemaira, according to the nonprofit Alpha-1 Foundation.

Martinez said Grifols has not evaluated the cost of each test or set a budget for how many tests it will distribute. The free testing program will be exclusive to the US as such tests can be provided only by prescription in Europe.

Ronald Crystal, chair of genetic medicine at Weill Cornell Medicine, said providing earlier diagnoses and treatments through Grifols' over-the-counter test could reduce long-term harm to patients. He has seen more than 500 patients with AAT deficiency during his career, often after those patients had already accumulated significant damage.

"I think it's useful to have these tests widely available — that's very positive," he said. "But people have to use them to be able to make the diagnosis. They have to be knowledgeable of the disease to want to do the test."

According to Grifols, about 16 million Americans are living with COPD, and while smoking is the primary cause, AAT deficiency is the top genetic cause of the disease. Clinical practice guidelines published by the journal Chronic Obstructive Pulmonary Diseases indicate AAT deficiency likely affects 1 in every 2,500 to 1 in 5,000 people in the US and Europe.

A more recent article published in 2020 in Chronic Obstructive Pulmonary Diseases indicates AAT deficiency is one of the most common genetic diseases yet only between 5 percent and 10 percent of people who have AAT deficiency receive the correct diagnosis. The article indicates the risk varies by the inherited mutations to the SERPINA1 gene. About 1 in 4,800 people are homozygous for the SERPINA1 Pi Z allele, putting them at risk of severe disease, whereas about 1 in 1,100 carry a Pi S and Pi Z allele combination that can contribute to disease development but are less likely to result in severe disease.

The earlier the diagnosis, the earlier those patients can begin receiving augmentation therapy, which involves weekly intravenous doses of AAT, Crystal said. Simple blood tests for AAT deficiency are widely available but, other than pulmonary specialists, doctors tend not to think about it or be aware of it, he said.

The hereditary disorder is often undiagnosed because it tends to produce subtle symptoms in nonsmokers, at least at first, Crystal said. While a smoker may develop those breathing difficulties in their mid-30s to mid-40s, a member of the nonsmoking majority may not develop disease related to the condition for another 20 years.

AlphaID isn't the first over-the-counter AAT deficiency test on the market. The FDA granted 23andMe premarket authorizations for a slew of direct-to-consumer tests in 2017, including its AAT deficiency test that Grifols cited as a predicate device in seeking 510(k) clearance. The 23andMe genome service test for alpha1-antitrypsin deficiency is a saliva-based test for two variants in the SERPINA1 gene using magnetic bead-based DNA extraction and PCR analysis.

According to Grifols, an estimated 2 percent to 3 percent of COPD patients have AAT deficiency although it is rarely diagnosed, and the percentage of people who have liver disease and AAT is unknown.

Grifols plans to make the over-the-counter test available through a website that the company has been using to advertise its prescription test. The company will ship the testing kits directly to homes, where patients can collect saliva samples and ship them back to Grifols' CLIA laboratory for test processing. The company will send each patient a report in about five to seven business days indicating whether their test results suggest they are at increased risk of developing lung or liver disease compared with the overall population, slightly increased risk, not likely at increased risk, or at unknown risk. Grifols will also send recommendations that each patient with elevated risk visit their doctor, who can consider the results along with other clinical observations.

More than 80 percent of patients at increased risk will develop lung or liver disease during their lifetime whereas 20 percent to 80 percent of those at slightly increased risk will develop lung or liver disease, according to the FDA.

Martinez said the company hopes its efforts will increase awareness of AAT deficiency and help the 90 percent of patients who lack diagnoses.

"The aim is to improve the quality of life of these patients," he said. "It takes a long time to be diagnosed, so this is a very pioneering change to benefit the patient."

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