Jason M. Broderick

This article was originally published in UrologyTimes.

New insight shows the Pfizer and Moderna mRNA 

A research team from the University of Miami Miller School of Medicine assessed 45 healthy men (median age, 28 years) who received either the BNT162b2 mRNA vaccine (Pfizer-BioNTech) or the mRNA-1273 mRNA vaccine (Moderna).

In this population, the researchers did not observe reductions in any sperm parameters, including semen volume, sperm concentration, sperm motility, and total motile sperm count (TMSC).

“Vaccine hesitancy is a barrier to ending the COVID-19 pandemic, and we believe some of that hesitancy is due to public opinion about whether the vaccine might negatively affect fertility,” senior study author Ranjith Ramasamy, MD, associate professor and director of the Miller School’s Reproductive Urology Program, stated in a press release.

“We were the first to demonstrate that the COVID virus, itself, can affect male fertility and be a potential cause for erectile dysfunction. We are now the first to examine if there is any impact of the COVID vaccine on male fertility potential, which we did not find,” added Ramasamy.

The prospective, single-center study conducted at the University of Miami accrued 45 men aged 18-50 years between December 17, 2020, and January 12, 2021.

Overall, 21 men (46.7%) received BNT162b2 and 24 men (53.3%) received mRNA-1273 and semen samples were obtained at baseline and at a median follow-up of 75 days (IQR, 70-86) after the second vaccine dose.

The median abstinence periods before obtaining the samples were 2.8 days (IQR, 2-3) for the baseline sample and 3 days (IQR, 3-4) for the follow-up sample. The researchers completed the study on April 24, 2021.

“This is the full life cycle of sperm and 70 days is sufficient time to see if the vaccine impacts semen parameters,” Daniel C. Gonzalez, BSc, a medical student at the Miller School and the study’s first author, stated in the press release.

Across the 45 patients, the baseline sperm concentration was 26 million/mL (IQR, 19.5-34) and the follow-up sperm concentration was 30 million/mL (IQR, 21.5-40.5; 

 = .02). The baseline and follow-up TMSC values were 36 million (IQR, 18-51) versus 44 million (IQR, 27.5-98), respectively (

 = .001). The median semen volume was 2.2 mL (IQR, 1.5-2.8) at baseline and 2.7 mL (IQR, 1.8-3.6) at follow-up (

 = .01). The median total motility percentage was 58% (IQR, 52.5-65) versus 65% (IQR, 58-70), respectively (

The researchers noted that 8 men were oligospermic (median concentration, 8.5 million/mL; [IQR, 5.1-12]) prior to receiving the vaccination. Among this subgroup, only 1 man remained oligospermic after vaccination, and the other 7 men actually had an increase in their sperm concentration to normozoospermic range at follow-up (median concentration, 22 million/mL; [IQR, 17-25.5]). The investigators reported that no men became azoospermic after being vaccinated.

In their study conclusion, the author’s wrote, “Because the vaccines contain mRNA and not the live virus, it is unlikely that the vaccine would affect sperm parameters. While these results showed statistically significant increases in all sperm parameters, the magnitude of change is within normal individual variation and may be influenced by regression to the mean. Additionally, the increase may be due to the increased abstinence time before the second sample.”

Sperm Parameters Before and After COVID-19 mRNA Vaccination

Articles

The vaccines did not result in reductions in semen volume, sperm concentration, sperm motility, and total motile sperm count.

Moderna, Pfizer COVID-19 Vaccines Do Not Affect Male Fertility

Array BioPharma Inc released its financial results for the third quarter of fiscal 2010, reporting $18.4 million in total revenue for the period but a net loss of $15.2 million, or $0.30 per share. The numbers are an improvement over the third quarter of fiscal year 2009, when Array posted revenue of $6.0 million and had a net loss of $29.6 million, or $0.62 per share. At the close of the third quarter, Array had $100.3 million in cash, cash equivalents, and marketable securities, a figure that excludes the $45 million Array will receive during the fourth quarter from its recent partnership with Novartis International AG. 

The agreement licensed Array’s cancer drug ARRY-162, along with similar drugs, to Novartis for a potential $467 million in payments and royalties. News of the partnership initially caused Array shares to spike 35%; however, the increase retreated after Swiss bank UBS downgraded Array’s stock from a rating of “Buy” to “Neutral.” UBS based its assessment on the early development stage of most of Array’s pipeline and Array’s deals with Novartis and Amgen (ARRY-403 for type 2 diabetes) limiting the company’s need for additional partnerships. 

Robert E. Conway, CEO of Array, disagrees with UBS’ value assessment. “Based on our current assumptions, our analysis of the estimated risk-adjusted net present value of [the] potential income from our partnered drugs alone significantly exceeds the current market capitalization of the company,” he said. He pointed out that the recent deals with Novartis and Amgen would “provide Array with $105 million in initial payments, over $1 billion in potential milestone payments, double-digit royalties, and commercial co-detailing rights.” In addition to the substantial benefit Array derives from its multiple partnerships, Conway noted that the company’s primary asset is its proprietary pipeline, which has numerous compounds owned 100% by Array.

Array’s oncology pipeline includes inhibitors of HER2, EGFR, KSP, p38, and Tie-2. Eight abstracts disclosing data from studies of several of these anticancer drugs were presented at the 

American Association for Cancer Research 101

, held from April 17 to 21, 2010, in Washington, DC. 

Array is working with Novartis to develop MEK162 (ARRY-162) and MEK300 (ARRY-300), and other MEK inhibitors. With the maximum tolerated dose of MEK162 now established, Array is proceeding with expansion of a phase I trial in patients with biliary tract cancer, which is taking place at 10 trial locations in North America. The expansion study will be evaluating the pharmacokinetics and pharmacodynamics of the drug, along with tolerability. Array hopes MEK162 will prove successful in multiple indications.

ARRY-520, a kinesin spindle protein inhibitor, is in phase I trials in patients with solid tumors and in phase I/II trials for patients with acute myeloid leukemia and multiple myeloma. Array hopes to complete these trials in the current fiscal year. In a proof-of-concept study, investigators are evaluating the activity and safety of the p38/Tie-2 inhibitor ARRY-614 in a phase Ib/II trial of patients with myelodysplastic syndromes. 

Three phase Ib trials evaluated ARRY-543, an ErbB-family inhibitor, in combination with other agents as a treatment for solid tumors. One looked at ARRY-543 in combination with capecitabine (Xeloda), another with docetaxel (Taxotere), and the third with gemcitabine (Gemzar). Researchers reported that these trials have established the maximum tolerated dose of ARRY-543. They expect to present updated data at a selected conference later this year and are moving forward with plans for a phase II combination trial. ARRY-380 is a HER2 inhibitor being studied in a dose-escalation, phase I trial of patients with advanced cancer.

In addition to the new deal with Novartis on its MEK inhibitors, Array has an arrangement with AstraZeneca to continue development of AZD-6244, a MEK inhibitor being investigated in KRAS-mutated non—small cell lung cancer and BRAF-mutated melanoma. The company reported that AstraZeneca is continuing with two phase II combination trials of AZD-6244 combined with MK-2206, an AKT inhibitor being developed by Merck. 

Array has partnerships with Amgen, InterMune, Eli Lilly, Celgene, and Genentech to develop existing drugs or collaborate on the development of new drugs, not only in oncology but also in diabetes and immune disorders. Array recently estimated the net present value of its partnered and wholly owned programs at more than $800 million.

Array BioPharma Inc released its financial results for the third quarter of fiscal 2010, reporting $18.4 million in total revenue for the period but a net loss of $15.2 million, or $0.30 per share.

Array BioPharma Has No Shortage of Partners

A struggle with cancer is often referred to as a battle. Now, a study reveals patients with cancer and caregivers even experience a condition common to soldiers, post-traumatic stress syndrome. The disorder does not arise from cancer’s primary theater of conflict, the tumor site, but rather from a secondary battlefield, the patient’s wallet. The report, issued by the nonprofit Cancer Support Community (CSC), in conjunction with biotech company Genentech Inc, found the financial burden of cancer costs leaves patients and caregivers vulnerable to anxiety, depression, and other mental health issues. Eighty-one percent of patients and 72% of caregivers surveyed reported “moderate to severe” levels of stress due to financial issues.

According to Joanne S. Buzaglo, PhD, senior director of research at CSC, researchers were surprised by the severity of the condition. “It is hard to imagine, but the levels of post-traumatic stress reported were even greater than that of those who witnessed the terrorist attacks in New York City on September 11 and akin to that of underprivileged, displaced survivors of Hurricane Katrina.”

The study, entitled “Evaluation of the Challenges and Barriers to Accessing Financial Support for Cancer Patient Treatment,” differed from previous research in that it used a standardized measure to analyze symptoms of post-traumatic stress related to cancer costs. Researchers surveyed an ethnically diverse group of 105 patients and caregivers. Over half of the respondents were employed. Twenty-five percent of patients and 18% of caregivers surveyed had household incomes of  <$20,000/y. Ninety-one percent of patients had insurance coverage, with 19% using Medicare or Medicaid. 

For several individuals, the distress arose from an inability to afford medical bills totaling thousands of dollars. Others reported insurance coverage issues, including calendar-year limitations on appointments with specialists. For most, attempting to solve the fiscal crisis only worsened the despair. Many patients began sacrificing their health, skipping medication doses, or selecting inferior, less expensive treatments. Others depleted savings, borrowed money from family or friends, or started working a second job. 

As their fiscal problems mounted and stress levels rose, respondents experienced several barriers to needed assistance. Approximately 50% of patients lacked the funds for mental health support. Nearly half of patients were unaware of financial assistance programs, while others feared they would not qualify for aid or were unwilling to face financial scrutiny. Some were simply too exhausted and overwhelmed from their cancer treatment to pursue assistance. “Those with the greatest economic need often fail to seek out assistance due to the distress they are experiencing,” said Buzaglo.

Those who did seek financial assistance found the Internet and social workers to be the best information sources. Some patients (34%) were enrolled in pharmaceutical or copay assistance programs. For more on the study, go to 

A struggle with cancer is often referred to as a battle. Now, a study reveals patients with cancer and caregivers even experience a condition common to soldiers, post-traumatic stress syndrome.

Overwhelming Cancer Costs Can Cause Post-Traumatic Stress  

The American Society of Clinical Oncology (ASCO) updated its 2003 recommendations for genetic testing to keep pace with exponential progress in genetic science. The new guidelines encompass developments in genetic testing from the past 7 years, including direct-to-consumer (DTC) genetic testing and public access to genetic tests with unproven clinical benefit. A podcast and article summarizing the recommendations are available at www.cancer.net.

“The awareness of individual genetic differences within the population has sparked a number of significant developments and an unprecedented level of raw information being made available, not only to health professionals, but also to the public in the form of DTC tests,” said Kenneth Offit, MD, MPH, chief of Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center, and chair of ASCO’s Ethics Committee, in a press release. “ASCO’s updated recommendations on genetic and genomic testing attempt to get back to the basics— patient safety and clinical utility&mdash;for the individuals considering genetic testing and the doctors who offer testing or may be asked by patients to interpret DTC test results,” he said.

Genetic testing can help assess the risk of disease, identify genetic carriers, diagnose disease, or predict the course of a disease. Currently, genetic tests are available for malignancies of the breast, ovaries, and colon, and for some rare cancers. Most tests have been professionally mediated and have proven clinical usefulness. DTC genetic testing and those tests for which clinical usefulness has not been demonstrated scientifically fall short of the new ASCO standards. ASCO believes that tests with unproven clinical utility, like tests to identify genetic variations and assess cancer risk, need to be evaluated in clinical trials. ASCO also supports indicating which tests have personal, but not clinical, utility.

In 2004, the Centers for Disease Control and Prevention (CDC) established the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) to help evaluate genetic tests and genomic applications and their transition from research to practice. The EGAPP Working Group has developed processes for assessing the validity and utility of a genetic test in clinical practice, but the CDC has no authority to regulate genetic testing, which falls under the purview of the FDA. ASCO proposes that the FDA and Centers for Medicare and Medicaid Services develop standards to assess the accuracy, validity, and quality of genetic tests and genetic testing facilities. According to ASCO, creating a compulsory public registry that requires manufactures of genetic tests to make full disclosure would facilitate better oversight.

ASCO advises individuals to use caution when using genetic technologies that do not meet the new standards. According to ASCO, people using DTC tests should consult their healthcare provider for assistance with interpreting results and for advice on follow-up care, based on established cancer risk factors. As the price of genetic testing continues to fall, with recent full screening now available for $5000, more people may request genetic screening to assess their risk for various cancers, making it increasingly important to develop guidelines and regulations for those who manufacture and distribute genetic tests.

ASCO urges renewed focus on establishing higher standards for genetic testing in oncology. Beyond professional mediation and clinical practicality, ASCO advocates the following: genetic tests need interpretable results, individuals tested should demonstrate genetic cancer susceptibility, and individuals should receive pre- and post-test counseling.

The American Society of Clinical Oncology (ASCO) updated its 2003 recommendations for genetic testing to keep pace with exponential progress in genetic science.