FDA to Lift Ban on Blood Donations from Gay Men, the House Approves the 21st Century Cures Act, and more

FDA Plans to Lift Ban on Blood Donations from Gay Men

In 1983, shortly after the onset of the AIDS epidemic, the U.S. Food and Drug Administration (FDA) advised blood centers to refuse blood donations from gay men for fear of contaminating the blood supply. However, the FDA recently concluded that contemporary practices of blood screening render the ban unnecessary.

In a formal proposal issued on May 12, 2015, the FDA recommended ending the 32-year-old ban on blood donations from men who have sex with men (MSM), provided they haven’t had such sex in the previous 12 months.

This proposal is a follow-up to the agency’s announcement last December that it intended to issue a proposal to lift the ban in 2015. Last year, two separate federal advisory committees recommended this one-year deferral policy as safe, based partly on the experience of the United Kingdom, Sweden, Japan, Australia, and other countries that already had adopted it.

However, groups in the lesbian-gay-bisexual-transgender (LGBT) community object to the requirement that MSM must be sexually abstinent 12 months prior to donating blood, contending that current blood donation testing detects all known serious blood-borne pathogens, including HIV, within 45 days of exposure. A shorter deferral, of two months or less, may be appropriate, they suggested.

The American Civil Liberties Union also took issue with the FDA plan. “The FDA’s proposal must be seen as part of a continuing process and not an endpoint,” said Ian Thompson, ACLU legislative representative. “The reality for most gay and bisexual men – including those in committed, monogamous relationships – is that this proposal will continue to function as a de facto lifetime ban.”

Peter Marks, MD, PhD, deputy director of the FDA’s center for biologics evaluation and research, said that compelling scientific evidence to shorten the deferral policy to less than one year is not yet available. Furthermore, medical data from other countries with the 12-month deferral policy in effect demonstrate that the limit does not lower the safety of the blood supply. He also described the policy as being consistent with other limits. For instance, there is a one-year deferral for men or women who have had sex with someone who is HIV-positive and for men or women who had sex with an intravenous drug user.

“The FDA has carefully examined and considered the available scientific evidence relevant to its blood donor deferral policy,” said FDA Commissioner Margaret A. Hamburg. Now, she said, the FDA “will take the necessary steps to recommend a change to the blood donor deferral period.”

The FDA did note that this new proposal does not reflect any shortage of blood donations, and there is not an urgent need to increase the number of eligible blood donors.

The proposed FDA guidance to blood centers was officially published in the Federal Register on May 15 and is now open for public comment. When the 60-day window for public comment closes, the FDA will issue a final version of the recommendations.

Sources: The Wall Street Journal and the FDA’s “Revised Recommendations for Reducing the Risk of Human Immunodeficiency Virus Transmission by Blood and Blood Products: Draft Guidance for Industry”

Researchers Make Progress in Making All Blood Types Universally Accepted

Scientists have made promising progress in developing a method for transforming any type of donated blood into type O – the universal blood type that can safely be given to any patient – according to research published in the Journal of the American Chemical Society. Led by David H. Kwan, PhD, a team of scientists created a special enzyme that can shear off the substances on red blood cells that are responsible for potentially fatal immune reactions if a patient receives the wrong type of blood.

The enzyme is not yet effective enough to allow for large-scale processing to convert type A or type B blood into type O, said Dr. Kwan, a postdoctoral fellow of chemistry at the University of British Columbia’s Centre for Blood Research in Vancouver, Canada. “We’re not there yet. This is a step toward that,” Mr. Kwan said. “The big thing is that we’ve shown that it’s feasible to improve these enzymes.”

The enzymes used in the study strip away antigens that determine blood type; while the methodology has been around for about 15 years, this is the first promising report of its effectiveness. Mr. Kwan and his colleagues performed what’s called “directed evolution” on the enzyme, generating mutant versions and selecting the ones that did the best job of stripping away blood antigens. In just five generations, the enzyme became 170 times more effective – not yet effective enough to solve the problem of ABO mismatch, the researchers said, but improved enough to show that the process of enhancing the enzyme does work.

If this technology proved effective in converting any-type blood into the universal donor type O and feasible on a large scale, the effect would be transformational. Blood banks tend to lean heavily on donors who are type O, particularly if their blood also is RH-negative, the authors noted. About 11 percent of hospital transfusions involve donated type O, RH-negative blood; however, this specific blood type is in short supply, with only about 6 percent of the population carrying it.

“This is a significant step toward developing [methods] for the complete removal of blood group antigens,” the authors wrote, “allowing for blood transfusions and organ and tissue transplants from donors that would otherwise be mismatched.”

Source: Kwan DH, Constantinescu I, Chapanian R, et al. Toward efficient enzymes for the generation of universal blood through structure-guided directed evolution. J Am Chem Soc. 2015;137:5695-705.

FDA Approves New Recombinant Factor IX Product for Hemophilia

The U.S. FDA approved a recombinant factor IX (rFIX) product for the control and prevention of bleeding episodes, as well as for perioperative management in adults and children 12 years of age or older with hemophilia B. The FDA’s approval was based on results from global, multicenter phase I/III clinical studies evaluating the rFIX product’s safety, efficacy, and pharmacokinetics in previously treated patients with severe to moderately severe hemophilia B. In these trials, one or two infusions of the rFIX product resolved 84 percent of the bleeding episodes participants experienced. Pharmacokinetic study results showed that the newly approved rFIX product achieved similar behavior to another licensed recombinant coagulation factor IX product on the market. In addition, administration of the rFIX product resulted in hemostasis in study participants who underwent major surgical procedures. The most common adverse drug reactions included headache, weakness, apathy, lethargy, and injection site discomfort.

Source: FDA news release

IBM’s Watson Supercomputer to Help Guide Cancer Therapies at 14 Centers

Starting in late 2015, 14 U.S. and Canadian cancer institutes will use the IBM’s Watson computer system to choose therapies based on a tumor’s genetic fingerprints in an effort to bring precision cancer treatments to more patients. Pioneering precision medicine approaches have shown to be effective in some areas of oncology, where matching therapy to DNA has the potential of improving patient outcomes. However, finding the right drug to target the cancer-causing DNA mutations can take weeks. Watson, with its database of clinical trials and research papers on particular cancers and potential therapies, can do it in minutes. Using a “big data” approach to genomic analysis, Watson will sift through thousands of mutations to try to identify which mutations in a patient’s DNA fingerprint are drivers of the malignancy using a scoring system to distinguish these mutations from others. The computer system will then match the actionable targets to approved and experimental drugs. For now, chemotherapy and radiation will remain the standard of care for common cancers, but faced with so much genomic data, “the solution is going to be Watson or something like it,” said oncologist Norman Sharpless, MD, professor of medicine and genetics at the University of North Carolina’s Lineberger Comprehensive Cancer Center, one of the participating centers. “Humans alone can’t do it.”

The collaborating centers include: Ann & Robert H. Lurie Children’s Hospital of Chicago; BC Cancer Agency in British Columbia; City of Hope, in Duarte, California; Duke Cancer Institute in North Carolina; McDonnell Genome Institute at Washington University in St. Louis; New York Genome Center; Sanford Health in South Dakota; University of Kansas Cancer Center; University of Southern California Center for Applied Molecular Medicine; and University of Washington Medical Center.

Source: Reuters

FDA Grants Breakthrough Therapy Designation to BCL-2 Inhibitor in CLL

The U.S. FDA has granted breakthrough therapy designation to the investigational drug venetoclax for previously treated patients with relapsed or refractory chronic lymphocytic leukemia (CLL) with 17p deletion. Venetoclax is an oral B-cell lymphoma-2 (BCL-2) inhibitor designed to selectively inhibit the function of the BCL-2 protein. The BCL-2 protein prevents apoptosis of some cells, including lymphocytes, and can also be expressed in other cancer types. Venetoclax is currently under evaluation in phase II and phase III trials in patients with CLL and other malignancies. Approximately 30 to 50 percent of patients with relapsed or refractory CLL harbor the 17p deletion, and the median life expectancy for these patients is less than two to three years. The new investigational drug was associated with high objective response rates as a single-agent and in combination with rituximab in earlier phase Ib trials.

Source: AbbVie press release

House Committee Approves the 21st Century Cures Act to Accelerate Drug Approvals

On May 21, a U.S. House of Representatives committee unanimously approved a bill, known as the 21st Century Cures Act, that would bring new drugs to the market more quickly. The bill, developed by the House Energy and Commerce Committee, requires the U.S. FDA to incorporate patient experience into its decision making, streamline its review of drugs for additional uses, and consider more flexible forms of clinical trials. The draft of the bill calls for the Secretary of Health and Human Services to create pathways that would expand access to new cures for patients and ease the regulatory burdens involved in developing new cures, including clinical trials. Offsets would also include certain changes in government payments to insurance companies and a reduction in Medicaid payments for some medical equipment.

In addition, the Cures Act incentivizes projects that repurpose existing therapies for other indications and directs funding efforts at boosting research in areas of unmet need. The Cures Act would increase funding to the National Institutes of Health by $10 billion and boost FDA funding by $550 million over five years. While the bill was cheered by patient advocacy groups, critics fear that it will weaken the FDA’s ability to restrict marketing of drugs for unapproved uses and potentially lower safety and efficacy standards by relying on less rigorous clinical data.

Source: Reuters

FDA Updates Pomalidomide Labeling With New Multiple Myeloma Results

The U.S. FDA has updated the label for pomalidomide plus low-dose dexamethasone to include data from the phase III MM-003 study, which reported a significant extension of progression-free and overall survival, versus high-dose dexamethasone alone, in patients with relapsed/refractory multiple myeloma.

In the phase III study, 455 patients with multiple myeloma who had received prior treatment for at least two regimens (including bortezomib and lenalidomide) were randomized to receive either pomalidomide plus low-dose dexamethasone (n=302) or high-dose dexamethasone alone (n=153). Patients had received a median of five prior therapies – 95 percent were refractory to lenalidomide, 79 percent were refractory to bortezomib, and 75 percent were refractory to both. Median progression-free survival was 3.6 months in the combination group versus 1.8 months with high-dose dexamethasone alone (HR=0.45; 95% CI 0.35-0.59; p<0.001). Patients taking pomalidomide also experienced greater median overall survival than patients taking high-dose dexamethasone (12.4 vs. 8.0 months; HR=0.70; 95% CI 0.54-0.92; p=0.009).

In February 2013, the FDA granted pomalidomide an accelerated approval as a treatment for patients with multiple myeloma following two prior therapies, including lenalidomide and bortezomib.

Source: Celgene press release