American Society of Microbiology (ASM) 2021 World Microbe Forum

 infection (CDI) treatment resulted in a low recurrence rate when compared to placebo.

A team led by Colleen S. Kraft, MD, Emory University School of Medicine, evaluated the distribution of C difficile ribotypes and whether CDI recurrence was related to relapse or reinfection in patients with multiply rCDI.

The researchers previously tested an investigational microbiome therapeutic consisting of purified Firmicutes spores called SER-109 in an attempt to identify the typing of strains from infections to learn more about CDI disease and epidemiology.

“SER-109 may represent a paradigm shift in the clinical management of patients with recurrent CDI,” the authors wrote.

C difficile infections are generally caused by the disruption of the microbiome coupled with exposure to C difficile spores. The leading risk for infections is the exposure of broad spectrum antibiotics, which can cause collateral damage to beneficial microbes that normally reside in the gastrointestinal microbiome.

In addition, there is a current lack of antibiotics that target C difficile due to a lack of effect on C difficile spores that germinate within a disrupted microbiome, preventing a sustained response in the majority of patients.

The researchers previously found SER-109 was superior to placebo in reducing the recurrence of CDI during an 8 week phase 3 study (12.4% vs 39.8%; RR, 0.32; 95% CI, 0.18-0.58; 

Strain typing data is generally not available to assess whether recurrence is due to relapse or reinfection.

In the ECOSPOR III study, the researchers used selective media to isolate C difficile from baseline stool samples and stool samples from unscheduled visits for recurrence of diarrhea during a 24 week follow-up period. Each participant’s baseline stool sample was taken before randomization without regard to whether the patient had started or completed the standard-of-care antibiotic treatment.

The team also isolated C difficile from ethanol treated stool using C difficile selective agar—Cycloserine-cefoxitin-fructose agar with and without horse blood—as well as enrichment culture—Cycloserine Cefoxitin Mannitol Broth with Taurocholic Acid Lysozyme and Cysteine.

In addition, the investigators saved 1 C difficile isolate per stool sample and typed strains by PCR ribotyping.

In a post-hoc analysis, the researchers evaluated the distribution and prevalence of ribotypes in patients and determined whether the ribotype at recurrence was indicative of relapse or reinfection for up to 24 weeks.

In total, 122 patients (67%) yielded positive cultures at baseline, while 10 (5.5%) yielded no growth. In addition, 50 (27.5%) subjects did not contribute a sample. Overall, there were 33 different ribotypes at baseline with 020/014 the most common ribotype, which was identified in 18.9% of baseline patients.

Hypervirulent ribotypes 027 and 078 (0787/126) were also identified in 15.6% (n = 19) of the patient population at baseline.

A total of 47 recurrences were observed, 11 in the SER-109 arm and 36 in the placebo group. Of those, paired ribotypes were available for 32 recurrence events, including 9 in the treatment group and 23 in the placebo group.

Relapses were also more common in the study (n = 24; 75%).

However, relapse events were lower in patients treated with SER-109 (5 vs. 19). Reinfection events were comparable, but low (4 vs. 4).

“SER-109 significantly reduced CDI recurrence compared to placebo at 8 weeks after dosing with an observed safety profile comparable to placebo,” the authors wrote. “Multiple ribotypes were isolated, which is consistent with typically observed epidemiological studies. Low rates of recurrence with SER-109 observed in ECOSPOR III limit the ability to assess the impact of relapse versus reinfection; however, numerically, SER-109 demonstrated reduced rates of recurrence compared with placebo across ribotypes and protected against the dominant mode of recurrence (relapse) in patients with a history of multiply recurrent CDI.”

The researchers are currently enrolling patients with at least 1 episode of CDI for an open-label study.

Characterization of Ribotypes Among Study Participants in a Phase 3 Trial of Investigational Microbiome Therapeutic SER-109 to Reduce Recurrent Clostridioides difficile infection (rCDI)

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Strain typing data is not often available to assess whether recurrence is due to CDI relapse or reinfection.

SER-109 Reduces Rates of Recurrent C Difficile Infections

The US Food and Drug Administration (FDA) has approved dabigatran etexilate (Pradaxa) oral pellets for the treatment of children 3 months to <12 years old with 

With the indication, dabigatran etexilate is the first FDA-approved blood-thinning therapy for pediatric oral administration, with all previous agents available only in injection form. It was originally approved in 2010 for the reduction of stroke and systemic embolism risk in adult patients with non-valvular atrial fibrillation.

The therapy is specifically indicated for pediatric patients with VTE directly following injection blood thinner therapy for ≥5 days, and includes an indication for the prevention of recurrent clots in the same patient population who completed treatment for their first VTE.

The FDA additionally approved dabigatran etexilate in capsule form, for the treatment of blood clots in patients ≥8 years old with VTE directly after ≥5 days of blood thinner injection therapy, and to prevent recurrent clots in the same patient population after completing treatment for their first VTE.

The efficacy and safety of dabigatran etexilate in treating pediatric blood clots was assessed in a single open-label trial involving 267 patients aged ≤18 years old. Patients were randomized to either dabigatran etexilate or standard of care, with investigators comparing the treatment groups for number of patients to reach the composite endpoint:

Nearly half (n = 81; 45.8%) of patients administered dabigatran etexilate had achieved the composite endpoint, versus 42.2% (n = 38) of the 90 patients administered standard of care.

Another open-label, single-arm pediatric assessment of 214 patients with a history of blood clots evidenced the safety of the therapy, with just 1.4% (n = 3) patients treated with dabigatran etexilate experiencing a recurrence of blood clots.

The most common adverse events in treated pediatric patients included digestive system symptoms and bleeding. Pradaxa includes a boxed warning advising that early treatment discontinuation may be associated with increased risk of blood clots.

In a statement accompanying the approval, Ann Farrell, MD, director of the FDA’s Center for Drug Evaluation and Research’s Division of Non-Malignant Hematology, emphasized the importance of simplicity in treating a possibly fatal event risk in children.

"The FDA is committed to helping our youngest patients with serious medical conditions have treatments that are relatively easy to take,” Farrell said. "With today's approval of Pradaxa, pediatric patients have another therapeutic option to treat and prevent potentially deadly blood clots."

Dabigatran etexilate was approved in both oral pellet and capsule forms for varying pediatric patient populations.

FDA Approves Oral Blood-Thinning Drug For Children with VTE

This article was originally published in ContagionLive.

China has officially passed the 1 billion dose mark for 

 vaccinations administered, becoming 1 of the world’s fastest inoculation efforts.

Despite the high number of doses given out, the country is still remaining very strict with its elimination efforts.

The borders are still mostly closed off to international travel, and social distancing measures are still being strongly enforced in some areas.

China has also been offering millions of its vaccines to other countries, but many places, like Brazil, are refusing the shot in hopes of getting Pfizer or Moderna’s vaccine.

In Cuba, officials are reporting that their homegrown COVID-19 vaccine, Soberana 2, is showing promising results.

On Saturday, results from a late-phase trial were reported, showing the vaccine to be 62% effective with 2 out of its 3 recommended doses.

The country has shunned foreign-made vaccines, putting all of their hopes in their own. Cuba has partnered with Iran, which has also boycotted foreign made vaccines.

The Philippines has recently agreed to purchase 40 million doses of the Pfizer-BioNTech vaccine, which will provide a significant boost to the country which has been struggling with infections.

The order is set to be delivered through the third and fourth quarter of 2020.

Since the start of the pandemic, the Philippines has seen over 1.35 millions COVID-19 infections, with 23,500 deaths.

Data Table per Our World in Data (June 20, 2021, 12 AM EST)

In the United States, Rochelle Walensky, the director of the US Centers for Disease Control and Prevention, warned on Friday that the Delta variant is soon likely to become the dominant strain in the country. The more transmissible variant is likely to spread throughout the unvaccinated population.

Data Table per CDC COVID-19 Tracker (June 20, 2021, 6 AM EST)

For more information on COVID-19 vaccination research, distribution, and assessment, check out some of these recent Contagion stories:

Emergency Use Authorization vs. Full Approval: What are the Implications?

Update on CureVac COVID-19 Vaccine Phase 2b/3 Trial

What Role Will Novavax’s Vaccine Play in the Global COVID-19 Effort?

Africa sees third wave as only 1% of the population is fully vaccinated.

China Hits 1 Billion COVID-19 Vaccines Administered 

It can be a long, painstaking process to develop new drugs for any disease.

 (IBD) treatments due to the advent of biologics has been impressive for many in the industry.

, Jean-Frederic Colombel, MD, Director Inflammatory Bowel Disease Center Icahn School of Medicine at Mount Sinai, explained the added value biologics have given to IBD treatments and why there still remains some gaps in treatment for this patient population.

Colombel recently took part in a HCPLive® State of the Science event called Institutional Perspectives in Gastroenterology: Inflammatory Bowel Disease, which was chaired by Bruce E. Sands, MD, Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai Hospital and the Dr. Burrill B. Crohn Professor of Medicine.

Some of the biologics currently approved and showing success in treating either ulcerative colitis and Crohn’s disease include anti-TNF agents such as infliximab, natalizumab, and vedolizumab.

However, there is still a segment of patients that do not respond to this class of medications, highlighting the need for new biologics, as well as other classes of drug to help treat patients.

And while biologics have come a long way in a few short years, Colombel said it likely will take about a decade to develop and test new treatments.

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It could take up to 10 years to develop new treatments for inflammatory bowel disease.

Jean-Frederic Colombel, MD: The Commitment to Biologics for IBD

Findings from recent studies from Beni-Suef, Egypt called for a greater focus on developing rapid differential clinical diagnosis of COVID-19 among patients with respiratory diseases.

The team of investigators, led by Rania M. Sarhan, PhD, spoke of the prevalence of symptom screenings for patients, as COVID-19 and respiratory diseases often shared the same symptoms such as fever, pneumonia, lung infection and difficulty breathing.

Sarhan and colleagues collected data from 522 patients with either allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), and/or COVID-19. Participants ranged from 18-60 years old, and roughly 60% (n = 312) patients were women.

The participants were divided into 4 groups: asthmatic patients, asthmatic patients with allergic rhinitis, COPD patients, and COVID-19 patients.

The participants were further divided into 3 subdivisions of COVID-19 patients only, COVID-19 patients with COPD, and COVID-19 patients with asthma.

The data were collected from Beni-Suef University Hospital and Hospital of Chest Diseases in Beni-Suef, and analyzed for demographic and clinical features.

The prevalence of asthma and COPD in COVID-19 patients were nearly equal, totaling 30.7% and 35.1% respectively. However, patients with COVID-19 showed significant scarification as opposed to patients without the disease.

According to the study, chest CT scans conducted on patients with COVID-19 showed bilateral ground-glass opacity (GGO) with abnormal findings.

Additionally, patients with COVID-19 experienced different and worse symptoms than other participants in the study, despite some similarities being noted earlier in the study.

Fever, dry cough, diarrhea, loss of smell and taste senses, shortness of breath, and blue lips were significantly more prevalent symptoms in all COVID-19 patients. Despite this, no significant effects observed when controlled for age, gender or comorbidities.

The findings in Sarhan and colleagues’ study echo recent research into correlations between respiratory disease and COVID-19 risk. A collection of articles published at the American Academy of Allergy, Asthma and Immunology (AAAAI) 2021 Virtual Sessions indicated that asthmatic patients may not face a heightened risk of COVID-19 severity, hospitalization, or death.

Lakiea Wright, MD, of Brigham and Women’s Hospital and Thermo Fisher Scientific offered her perspective on the AAAAI findings in an interview with HCPLive.

The review and analysis showed the presence of asthma in COVID-19 patients did not result in greater hospitalization risk, length of hospital stay, admission to the intensive care unit, or death.

“It was really non-allergic asthma in this cohort that was associated with hospitalization for COVID…and in these patients, they were using bronchodilators and corticosteroids in the past 6 months,” Wright said. “In this cohort, asthma and COPD were risk factors for severe COVID, but it was really about the disease severity of the asthma and COPD that correlated, rather than corticosteroid use.”

Both the Egypt and AAAAI findings showed a greater need for clarification of ailments in asthmatic patients, especially those suffering from COVID-19.

While mortality rates do not differ between participant groups in either studies, Wright and the investigators from the Egypt studies came to the same conclusion.

Sarhan and colleagues suggested COVID-19 diagnosis in patients should be confirmed by ground-glass opacity and abnormal findings on chest CT, while Wright spoke on the ever-changing landscape that COVID-19 presented.

“I would say that there’s a lot of information out there, we’re still understanding it, and the pace at which we’re trying to understand SARS-CoV-2 and COVID-19 is just so rapid,” Wright said. “A really good take-home is that we have that meta-analysis suggesting asthma in general is not a risk factor for COVID-19, but we want to make sure that patients with asthma have their asthma controlled during the pandemic.”

“Differential Clinical Diagnosis and Prevalence Rate of Allergic Rhinitis, Asthma, and Chronic Obstructive Pulmonary Disease among COVID-19 Patients,” 

was published online in The International Journal of Clinical Practice.

Investigators suggest symptoms in asthmatic patients are more severe, although it does not result in higher mortality rates.

Asthmatic Patients Experience Harsher Reaction to COVID-19

A recent study out of Europe investigated the clinical efficacy and cost-effectiveness of stratified care, in comparison to the current practice for patients with 

It served as an updated version of the UK STaRT Back trial, which demonstrated stratified care’s superiority in improved clinical outcomes, reduced costs, and increased efficiency of healthcare delivery.

Investigators, led by Lars Morsø, University of Southern Denmark, Odense, adapted the trial to match Danish primary healthcare setting and guideline recommendations.

They found no differences in clinical outcomes between patients with non-specific LBP receiving stratified care, compared to usual care in Danish primary care.

Investigators performed a two-armed, parallel-randomized controlled trial (RCT).

Participants were recruited between 2015 – 2017, with the last 12-month follow up questionnaire completed in December 2018.

Further, inclusion criteria included adults ≥18 years with non-specific LBP with or without associated leg pain.

Exclusions included serious pathology, serious illness or influential comorbidity, psychiatric illness, spinal surgery during last 6 months, pregnancy, or currently receiving physiotherapy for LBP.

In addition, data was collected at baseline, and then at 3- and 12-month follow-up after randomization.

For outcomes on the 3 most common domain of treatment success in LBP, investigators collected data from the patient-reported LBP Roland Morris Disability Questionnaire (RMDQ), time off work, and patient-reported global change.

Secondary outcomes included pain intensity, participant satisfaction, wellbeing, healthcare resource utilization, and quality-adjusted life years.

After screening, investigators randomized 334 patients, half of the original intended number of study participants. Patients were allocated 1:1 to stratified care (n = 169) or current practice (n = 164)

At baseline, participants had a median age of 46 years, with 58% women. The team noted nearly one-third of patients had experienced LBP for more than 12 months.

Further, patients had a median pain severity score of 6 on a numeric rating scale of 0 – 10.

Investigators noted that the mean change in primary outcome of disability was similar in intervention and control arms at 3 months (5.9 versus 5.5) and 12 months (6.1 versus 6.5).

Thus, a non-significant mean score was found in RMDQ scores at 3 months (-0.5; 95% CI, -1.8 – 0.9) and at 12 months (0.4; 95% CI -2.1 to 1.3), with a mean difference of 0.1 (95% CI, -1.5 – 1.6)

At 3 months and 12 months, no overall differences were found in self-reported time off work, even in medium- and high- risk groups.

Investigators noted that the outcome of patient-reported global change showed small differences across arms.

At 12 months, differences between the intervention and the control arms were worse (6% vs. 9%), no change (32% vs. 32%) and better/much better (61% vs. 59%).

Investigators found that stratified care intervention resulted in fewer treatment sessions (3.5 versus 4.5), as well as lower total healthcare costs (13.4 versus 228, 

 = .002). They found no difference in cost-effectiveness.

The team concluded no differences were found in patients with non-specific LBP who received stratified care.

However, they noted that stratified care may result in fewer treatment sessions, as well as reduced costs related to prescription and x-rays.

“Although stratified care may be challenging to deliver, the SBT appears to have usefully informed clinical decision-making; this is in keeping with a previous study,” investigators wrote. “In the future, we would recommend assessing fidelity to the matched treatments and monitoring of the number of treatment sessions provided.”

Effectiveness of Stratified Treatment for Back Pain in Danish Primary Care: A Randomised Controlled Trial

,” was published online in the European Journal of Pain.

Patient-reported scores showed no overall differences across 3- and 12- month follow-up. 

No Significant Difference in Low-Back Pain Stratified Care Compared to Usual Care

New data shows zuranolone (SAGE-217/BIIB125) 50 mg provided statistically significant improvement in depressive symptoms compared to placebo at day 15 in patients with 

Stakeholders from Sage Therapeutics and Biogen announced the positive results from the phase 3, double-blind, randomized, placebo-controlled WATERFALL study showing the treatment met the predetermined primary endpoint, assessed by the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score.

The LS mean changes from baseline in HAMD-17 total score at day 15 for patients treated with zuranolone 50 mg was -14.1, compared to the placebo group with an LS mean score of -12.3 (LS mean difference, -1.7 points; 

In the WATERFALL study, the researchers evaluated the efficacy and safety of the drug in 543 adults with MDD aged 18-64 years old. Each patient enrolled in the study had a HAMD-17 total score of at least 24 at screening and day 1 prior to dosing.

For the past 6 decades, clinicians have mainly relayed on monoamine-based antidepressants to treat chronic MDD. This class of treatment is administered daily and require sufficient exposure and continuous use to maintain effect. However, the new treatment is a two-week, once-daily oral drug with a molecule designed to provide a rapid-acting, sustainable treatment option.

The safety analysis shows the treatment was generally well-tolerated and exhibited a safety profile consistent with previous clinical trials.

A total of 161 patients (60.1%) in the treatment cohort experienced a treatment emergent adverse event, compared to 120 patients (44.6%) in the placebo group. However, the majority of these adverse events were considered mild to moderate, with the most common events being somnolence 15.3% (vs 3.0%), dizziness 13.8% (vs 2.2%), headache 10.8% (vs 7.8%), and sedation 7.5% (vs 0.4%).

The majority of these events occurred during the 14-day treatment period.

In addition, 2 patients in both the placebo group and the zuranolone group experienced a serious adverse event, while no deaths occurred in either study group. Nine (3.4%) patients reported a treatment emergent adverse event that led to drug discontinuation in the treatment arm, compared to 4 patients (1.5%) in the placebo group.

Finally, there was no signal for withdrawal symptoms identified as assessed by the 20-item Physician Withdrawal Checklist (PWC-20), or for increased suicidal ideation or behavior as per the Columbia-Suicide Severity Rating Scale (C-SSRS).

“Sage’s expertise in the modulation of the GABA receptor pathway in the brain, coupled with insights on the treatment wants and needs of clinicians and patients, has resulted in our targeting a unique benefit/risk profile with the development of zuranolone supported to date by the data generated in the WATERFALL Study and the broader Landscape and NEST programs,” said Barry Greene, Chief Executive Officer at Sage Therapeutics, in a 

“We dared to imagine a different future for the treatment of MDD where patients have the potential to experience a rapid response that is well-tolerated and that may enable them to stay better with long periods free from depression symptoms, and free from daily chronic treatments and related side effects.”

The treatment was well-tolerated with a safety profile consistent with previous clinical trials. 

Zuranolone Reduces Depressive Symptoms in Phase 3 Trial

As the United States begins to emerge from the pandemic, healthcare providers continue to reflect on the impacts of the virus and lockdowns on patient with chronic, debilitating conditions. 

communities have fared during the pandemic and the challenge of building up trust during the ongoing national and global vaccination campaigns in these patients. She spoke to the importance and role of communities and local clinics in overcoming such deep-rooted hurdles.

HCPLive: Now we are starting to see the US and other countries with higher vaccination rates beginning to slowly open up and resume normal life. Looking back, what do you think this pandemic has revealed about sickle cell care? What are the lessons that have been learned?

As an important issue for sickle cell disease communities, the pandemic cannot be reiterated enough. Individuals with sickle cell disease primarily come from communities of color, right? As a community that has already been impacted by lack of of adequate health care, those issues compound the impact of the pandemic.

One of the things that we learned from our experience in the pandemic as healthcare providers—and this is me speaking anecdotally—is the importance of communication. When you have a team that you trust, to take care of your health, then you build a relationship with them over time.

I think that one of the most important lessons learned for me was the importance of staying connected with my patients during the pandemic. I needed to be able to give them high quality information about when to seek medical care and about how to continue to take their medications.

I needed to give them important information about what the signs were of COVID-19 infection, particularly in individuals with sickle cell who have acute chest syndrome. Imagine the potential for COVID-19 exacerbating that problem, right?

I had to tell them that although there was a message out in the community—that people who had symptoms of COVID-19 should stay at home—that may not be the case for individuals with sickle cell disease.

We had a big communication barrier. In certain cases, the messaging that was going out to the general population was probably not the message that many of us as healthcare providers wanted our patients living with sickle cell disease to hear. We have to really address those compounded barriers and try to make a way for individuals with sickle cell disease to get the care that th ey need.

Those things included telehealth to make sure that they could still get medical care without needing to come physically to the hospital. 

Again, I mention that communication effort—which was primarily through town halls, social media, awareness campaigns—so that they understood what signs of COVID-19 they should be watching out for. Then, that transitioned to messaging about the importance of getting the vaccine. 

And then I think that the other piece of what I thought was so important was the impact of George Floyd's death, which put stress on our communities. Because even at that, it meant that the local healthcare were impacted in black communities. 

Pharmacies were closed due to concerns about safety in their communities, often the same thing with local labs. So that meant that we had to rely on these other patterns of communication to make sure that individuals with sickle cell got what they need. 

And then finally, I think the other thing that is striking to me is that individuals with sickle cell disease are already compromised day to day, and they don't necessarily feel or experience some of the things that are causing problems in them.

Typically, sickle cell disease is characterized as a disease of recurrent acute pain episodes. They're unpredictable. But those are also just  a small fraction of what physicians are concerned about in sickle cell disease. The premature breakdown of red cells and chronic organ damage that can lead to premature death is a major issue too.

So, getting individuals on therapies like Oxbryta that address the underlying condition and can modify those problems is really important.

I would rather them go through a pandemic as healthy as possible and as protected as possible. So, it's very concerning to me that many individuals with sickle cell disease were not on disease modifying therapies before we went into pandemic. And I think now we have to change that and make sure that we're protecting them in the best way possible.

You mentioned the importance of messaging, particularly about vaccinations. Of course, this national and global campaign has been a massive logistical undertaking, especially for communities of color. What has that messaging and conversation looked like for these communities and for patients living with sickle cell disease? How do you work to build trust and confidence in them? 

I think you mentioned a very key word when you talk about vaccine confidence: And that's trust. Trust in the scientific community, trust in the medical community, and trust in your health care providers to give you the information that you need to make a good decision about whether or not the vaccine is the right choice for you.

Universally and unconditionally, I believe that the vaccine is the right choice for patients living with sickle cell. One of the things that we needed to do was to provide information to those living with sickle cell disease about the vaccine so that they could make an informed decision.

This meant addressing some of the myths that were out there in the community about the vaccine, such as that it was rushed and that it could actually lead to problems related to fertility. All of these myths we had to address in the sickle cell community, just like we had to address in the general population.

And then we had to give this message in a way that didn't judge. We had to acknowledge the fact that every individual has the right to make their own decision, including individuals living with sickle cell disease. Giving them the tools, the information that they needed to make these decisions was first and foremost.

I think the pattern that we saw was very similar to the general African American community. We had a portion of individuals that were ready to get the vaccine right away. And definitely, I had that.

We had to make sure that when they were ready for the vaccine that we could actually provide it. So, finding places where they could get the vaccine in their community, providing a place for them to get it in the hospital, or even in the clinic, where they routinely go was first and foremost. 

Then you have a population of individuals who want more information. They want to see how individuals in their own geographic and disease communities are doing with the vaccine. They needed more time to get educated.

Then there's just a small portion of individuals that were very reluctant to get the vaccine. But I honestly believe that those individuals are also individuals that over time will reconsider.

At first, we had very slow vaccine uptake in the sickle cell community at my institution, and so we had to do awareness campaigns, town halls, find ways of communicating, find ways to get individuals access to the vaccine.

Then we had to find a way for people who took the vaccine to share their experience with individuals with sickle cell disease. They would talk about how safe it was, and how, in their experience, it didn't exacerbate problems associated with sickle cell.

You can imagine there were challenges with making sure that the vaccine producers were including people in trials from communities of color. But I imagine there were a few people with sickle cell disease who were probably available to actually participate in these clinical trials.

So, we had to gather that information on the safety of the vaccine. Our patients at Children's Hospital went through the process and we found it very safe. Very few of them had major complications, and they now are fully vaccinated and hopefully going through the normal routine of getting back into a clinic community that is not as concerned about COVID-19 exposure.

I think we have a long way to go, though. And I think that we need to continue to spread this message about the vaccine to make sure that individuals with sickle cell have access to the vaccine and then to continue to provide information so that people can make good decisions.

Finally, it is important not to judge, or what I call vaccine shame. We need to understand that a lot of the times that the reason that individuals are less confident about the vaccine is that they may not have a trusting relationship with their healthcare team.

That means we have to go in and develop a community of trust, with shared experiences from other individuals with sickle cell disease, so that they can make an informed decision.

It really speaks to the power of community with individuals of shared and similar experiences. Like you said, that healthcare provider or care team is one piece of it, but it seems that those with shared conditions or experiences can also be an integral part of building this key trust and ensuring one another can get the best possible, high quality care.

And I think that that aspect of access to high quality care is the core of what we at GBT are really trying to emphasize.

I think that the other aspect of that is when you think about the communities where there are few sickle cell experts available to provide high quality care. This is a challenge of manpower that we are facing.

When we first launched the vaccine at our hospital locally, we were trying to do it on weekends, and in a group setting where individuals no matter their condition could come and get vaccinated. What we found is that when we made the vaccine available in our clinic—where individuals with sickle cell go to get care by their team—that's when we had the highest show rates.

One of the things that I would like to see with vaccine access over time is being able to get the COVID-19 vaccine from your routine health care provider. I think that that is going to be a challenge with all of the ways that the vaccine needs to be stored and trying to track the log of the vaccines to make sure that they're not wasted.

But I think that that is really going to be ideal for most individuals, which is to provide it at a time that is convenient for them by a team that they know.

In part I of the Q&A, Smith-Whitley discussed World Sickle Cell Day and the value it has for raising awareness of sickle cell disease communities and their challenges. 

This past year has brought unique challenges for sickle cell disease patients and communities of color. The ongoing vaccination campaign is yet another challenge that healthcare communities must find ways to overcome. 

Kim Smith-Whitley, MD: Sickle Cell, COVID-19, and Building Trust in the Vaccines

Today is World Sickle Cell Day, an opportunity for healthcare providers, advocates, and patients to reflect on and raise awareness for the state of care for 

While scientific and therapeutic advancements have been made for these patients, there is still so much work that needs to be done, notes Kim Smith-Whitley, MD, executive vice president and head of research and development at Global Blood Therapeutics. The issues that sickle cell communities consistently face, as exacerbated by their physical and socioeconomic vulnerabilities, are particular and nuanced.

Smith-Whitley spoke on the importance of World Sickle Cell Day, what it means for affected communities, the therapeutic advancements, and how healthcare providers can continue seeking educational opportunities to better care for their patients. 

HCPLive: What do you consider to be the importance of World Sickle Cell Day for you and the healthcare community?

 As I'm sure you're aware, sickle cell has been often overlooked, and communities have been impacted by healthcare disparities and social inequities. And although, as scientists, we took a deep dive into sickle cell disease to understand the genetic variation that actually led to this condition, but science kind of abandoned sickle cell patients in the process.

Despite the first person being described with sickle cell in 1910, we still do not have good access to high quality care in 2021.

So, I think that the spirit of World Sickle Cell Day— when it was sponsored by the United Nations in 2008—was to increase awareness of sickle cell. But I believe this was not only to increase awareness in general, but to increase awareness of the journey of those individuals living with sickle cell disease—to emphasize their experience, to emphasize the way that they have to deal with the stigma and the way that they have had limited access to therapies. 

We've been limited with a number of disease modifying therapies for sickle cell disease, only reaching 4 in November of 2019. So, when you compare that to other inherited rare diseases, it really is quite low in number, and that's a discrepancy that we need to impact.

For me, the spirit of World Sickle Cell Day is to raise awareness of those healthcare disparities and to emphasize the impact of the social inequities. Part of this spirit is to talk about the stigma that individuals with sickle cell disease have to overcome, particularly as individuals who are drug seeking for their pain episodes, and raise their voice. This is all to allow us to understand the experiences of those both nationally and globally with sickle cell.

You said there are few disease modifying therapies for patients with sickle cell. Can you just provide an overview of where we are now and what you see as hope and potential for the future?

One of the striking things to me is that, although sickle cell has been in the US since 1910, we really are not doing more than just supportive care for the majority of these patients. We use medications to treat the pain, but we don't have good therapies that treat the underlying cause of that acute pain.

And so, for individuals living with sickle cell disease, and really until the 1990s, we didn't have specific disease modifying therapies. We would use transfusion therapy to try to prevent complications or to lessen the severity of complications once they occurred.

We had antibiotics that we could use to decrease infections, which was very important to increasing survival in childhood and was the basis for newborn screening. But we really didn't have therapies that could prevent some of the complications of sickle cell disease—until hydroxyurea therapy.

And then we had an agent L-glutamine (Endari) that came along about 20 years later. This helped address the antioxidant stress associated with red cell health.

And finally, in November of 2019, we had two new therapeutic agents available for us: crizanlizumab (Adakveo) and voxelotor (Oxbryta). One of the wonderful things about these two agents is that these drugs were developed specifically for sickle cell disease.

When we had L-glutamine and hydroxyurea, we were kind of borrowing from other processes in order to apply them to sickle cell disease. But these two agents were directed specifically at sickle cell from the start.

And one of the things that was, I think, very beneficial about these two agents is that they came at a time where we were having almost a slump in awareness about sickle cell disease.

Crizanlizumab was used to decrease pain in individuals with sickle cell disease. It is a piece of lectin inhibitor that you get once a month through an IV in order to decrease pain episodes.

And then we have voxelotor, which is an agent that prevents sickle hemoglobin polymerization and improves red cell health. Subsequently, hemoglobin levels rise and the early destruction of red cells or hemolysis decreases. And I think that individuals have a sense of improved health when they're taking x-rays. 

These agents then came along, and then the pandemic hit. Now, individuals with sickle cell disease are probably less likely to hear about these agents because I'm sure that their medical teams were focused on trying to communicate the complications of COVID-19 infection, trying to educate them on how to lower their exposure.

One of the things that is distressing to me after having come through the pandemic is a lack of sense of urgency about getting these disease modifying therapies to individuals with sickle cell.

I think that there is a false sense of confidence in the sickle cell provider community and thinking that our patients are doing okay. Because they may be on hydroxyurea, they may not have  frequent pain episodes—but again, that is not preventing progression of chronic organ damage.

We really need to take a step back and look at what we need to do to get voxelotor in the hands of individuals with sickle cell disease. We should do our best to improve red cell health and to limit, hopefully, what I believe will be chronic organ damage in this patients.

What is your advice to healthcare providers who are looking to find more opportunities to educate themselves and others on sickle cell disease, its related complications, and the therapeutic options?

I think you should always listen to your patients and their families first. Talk to your patients about what they're experiencing and educate your patients about what's available to them.

When it comes to discussions around disease modifying therapies, this is an opportunity to bring individuals living with sickle cell disease into the decision making process. This is respectful and compassionate care, giving individuals the information that they need to make a decision alongside you.

And so, you should be educating yourself as a health care provider about what these options are. They should be going to conferences. Global Blood Therapeutics recently has been at EHA and at the FSCDR conferences. We are very prominent in the ASH meeting as well.

Educate yourselves by going to conferences, accessing information online, and learning more information about Oxbryta and the benefits that it can provide for individuals with sickle cell disease.

A sickle cell expert reflects on the state of care and access for sickle cell communities. 

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