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The Pandemic Supercharged Decentralized Trials, Now What?

For Andy Coravos the tipping point was the Biogen Conference in Boston, February 2020. While only about 100 people attended the meeting, it became one…

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Andrea Coravos, CEO, HumanFirst

For Andy Coravos the tipping point was the Biogen Conference in Boston, February 2020. While only about 100 people attended the meeting, it became one of the most notorious super spreader events of the COVID-19 pandemic, ultimately leading to an estimated hundreds of thousands of cases around the world (Science, Dec. 2020).

“From that point on it was all hands on deck,” says Coravos, CEO of HumanFirst, a San Francisco-based firm that helps pharma companies and hospitals evaluate, select, and use sensors for clinical trials or home care. “Suddenly, it wasn’t safe for people, even the sickest patients, to go to a clinic or hospital site.” Thousands of trials ground to a halt.

One of the keys to restarting those trials was incorporating digital measures. There were lots of tools available already, but the question was often “Is this tool properly validated – and for this condition? Is it cyber secure?” Coravos says. That’s exactly what her team does. So they jumped into action.

The issues were not just which devices worked best for the job, but what exactly should be measured. “Think about sleep,” Coravos says. “What exactly is sleep? Should you measure how long you stayed asleep? How often you sweated? How you felt in the morning? Could you lift your grandkids up the next day?” In many ways, this was a whole different world from the traditional trial process of giving patients drugs and then checking their vitals and labwork.

Coravos was not alone is mobilizing her team for a full-throttle shift to decentralized clinical trials (DCTs). For anyone in the clinical trial field, no matter how peripherally, the onset of the COVID-19 pandemic was dramatic.

Rosamund Round
Rosamund Round, Paraxel

Rosamund Round of contract research firm Paraxel called the company’s president as soon as she heard about the pandemic’s surge in China. Vice President of the company’s Patient Innovation Center, Round advised that Paraxel start pressing customers to switch to DCTs. “The majority of clients were onboard immediately,” she says. “We had some who said ‘We’re not worried, this will blow over in a couple of weeks,’ but they came along too soon enough.”

She adds that, “I cannot think of a time that innovation has moved so quickly. These last two years have been wild.”

While it was a trial by fire, the crisis was tempered by the fact that so many people had already been working on encouraging the adoption of DCTs. The tools, framework, and mindset for the shift was there, it was just a matter of putting it in action and bringing regulators along. What experts on the frontlines have learned from this experience is straightforward: It’s crucial to validate the tools, some of DCTs tools and methods are now here to stay, and flexibility is mandatory, because not all patients want to do DCTs.

“The embrace of decentralized clinical trials during the COVID-19 pandemic worked tremendously well,” says John Cassidy, Global Head, eClinical Product & Commercial at Labcorp Drug Development.

Dos and Don’ts

At first, the pandemic uncovered the low-hanging fruit – things that were being done inefficiently, just because they were always done that way.

Craig H. Lipset
Craig H. Lipset, DTRA

“There is no reason a patient needs to come into a clinic for gait analysis,” says Craig Lipset, co-chair of the Decentralized Trials Research Alliance (DTRA). “Especially if that’s going to be a hardship for them. Why not use a remote device? They will literally do more walking to get from the parking lot than they do in the clinic.”

This puts digital health technologies (DHTs) in a pivotal position. “People have access to more DHTs now, from fitness trackers to apps and they have become more accustomed to tracking health metrics and continuous monitoring,” says Yashoda Sharma, program director of the Digital Medicine Society (DiMe). But some patients prefer to visit a clinical site. Either they don’t want the intrusion of a home visit, or they may just like the experience of visiting with staff.

Yashoda Sharma
Yashoda Sharma
Digital Medicine Society

 

“We had one rheumatoid arthritis trial where we were planning for DCT,” says Round “But the patients said they actually preferred clinic visits.” Meanwhile, parents of kids with rare diseases or other conditions, and people with low level chronic diseases far preferred DCTs. The lesson, Round says, is “Don’t make assumptions. Ask patients. Ask them a lot of things, and ask them often.”

Teonna Woolford, CEO of Sickle Cell Reproductive Health, says she found the daily e-diary she had to keep more time-consuming than a visit to a clinic would have been, during the trial she was participating in as the pandemic unfolded. “Maybe it’s because I’m a CEO, so I’m very busy,” she says. “But it seemed like a trip to a clinic once in a while would have been less bother.” Woolford adds that time off work, gas, parking, etc. “adds up” and she understands that for some patients a DCT is probably the only way they can participate in a trial.

Teonna Woolford
Teonna Woolford, CEO
Sickle Cell Reproductive Health Education Directive

Another critical factor was the regulatory environment. While that has typically been a tough landscape to navigate, the pandemic prompted some agencies to fall in step. The FDA quickly issued a guidance, (FDA’s Guidance for Clinical Trial Conduct During the COVID-19 Pandemic).

But just as importantly, the FDA aligned with the European Medicines Agency (EMA) to make it easier to meet both agencies requirements. “For many years the FDA had their rules and the EMA had theirs. But during the pandemic they created a framework so we could meet both agency’s requirements without jeopardizing quality or safety,” says Rasmus Hogreffe, VP of DCT Innovation at Medable.

Kathy Vandebelt
Kathy Vandebelt, Global Head
Oracle Health Sciences

Oracle stepped up to help accelerate the evaluation of the COVID-19 vaccines, some of the most rapidly tested and evaluated products in history. The data giant was well positioned to help with this effort. “We are the best at this,” says Katherine Vandebelt, Global Head of Clinical Innovation for Oracle Health Sciences. “Data collection, data architecture, analytics. That put us in position to lead in remote monitoring, consent, and more.”

One project Oracle developed, v-safe, helped monitor reported side effects from COVID-19 vaccines via patients’ smartphone or computer. It is an app that allows a confidential health check-in, as well as surveys and other tools. The company reports that over a hundred million records are in the system.

Online Doctor Consultation
Credit: vorDa / Getty Images

That data has already proved very valuable. As early as June of 2021, a New England Journal of Medicine report documented, that: “Early data from the v-safe surveillance system, the v-safe pregnancy registry, and the VAERS do not indicate any obvious safety signals with respect to pregnancy or neonatal outcomes associated with Covid-19 vaccination in the third trimester of pregnancy.”

Finally, there is the pressing issue of logistics. Simply delivering medications to patients became a challenge during the pandemic. Companies such as Medable, Paraxel, and others are now touting their ability to deliver temperature-controlled drugs within tight time windows to ensure that patients receive their medications safely and in a timely manner.

What’s Next for DCTs

“Training and adoption for sites is an area that deserves additional focus and is necessary to the success of DCTs,” says Labcorp’s Cassidy. He points out that decreasing the burden and training curve of using DCT methodologies can broaden the reach of those trials and progress the industry towards broader flexibility in trial conduct.

Lipset was involved in the first all-remote trial under an investigational new drug (IND) application, which was carried out by Pfizer about a decade ago (Orri et al., Contemp Clin Trials, 2014). This was a randomized, placebo-controlled, Phase IV (REMOTE) trial to evaluate tolterodine extended release (ER) 4 mg for overactive bladder.

“Some things worked and some didn’t. We were open about both,” he says. But there was not much momentum for DCTs even after that trial. Lipset points out that the two “guardrails” of clinical trials are patient safety and data integrity. It’s not surprising, he says, that people in this industry are cautious.

While he admits there was a surge of DCT adoption during the pandemic, he says it is premature to fly the “mission accomplished” banner. “It is conceivable that such a conservative industry will slip back into its comfort zone,” he says.

But he also points to the facts that FDA and other regulators (e.g in Sweden and Denmark) seem DCT friendly now, many sponsors have made “sizeable” commitments to this approach, and there is lots of guidance on how to pursue it (See Sidebar: Playbooks, Guidances, and Endpoints).

Vandebelt sees a new push for more real word data (RWD). All this data from remote monitoring provides an opportunity for data aggregators such as Oracle she says. “What happened over the last two years was unprecedented, and it took a lot of money and energy.” Now there can be a focus on using that data in new ways.

Ramus Hogreffe
Ramus Hogreffe, VP, Medable

In keeping with that, Hogreffe anticipates a push toward “bring your own device.” As devices are standardized, which platform patients have for personal use will become less relevant. Digital sensors will be plug and play. Meanwhile, the number of people with access to internet is steadily increasing, reaching a record 5 billion this year.

Says DiMe’s Sharma, “Many of the challenges facing clinical trials in general, still exist. The two biggest are trust and access.” Sharma points out that many patients have little trust in the healthcare system now. “Without a support system of clinicians and study teams, patients may lose even more confidence in the system and become reluctant to participate.”

Another question is whether DCTs can address the nagging issue of diversity, including ethnic and LGBQT participation. Making trials more convenient for people with cellphones or adding home visits doesn’t naturally tend to increase diversity. Many companies and organizations, including DiMe and Paraxel, are now looking at this since it has become clear that diversity is a major issue in data integrity for clinical trials.

Besides the urgency of safety during the pandemic, there is data supporting DCTS. A recent study from Tufts Center for the Study of Drug Development found that, on average, decentralized trials achieved a net financial benefit ranging from 5 to 14 times for Phase II and III trials through reduced trial timelines and other factors.

Working through issues like e-consent, logistics, and security have helped the pioneers of DCTs not only weather the pandemic, but thrive because of it. Participating in a clinical trial should be as smooth as buying on Amazon,” says Medable’s Hogreffe. “One click and you are in.”

He adds that taking about 12 years to bring a drug to market “Is unambitious. People want to invest their time in something more productive.”

Round had a personal view of the crisis as she had COVID-19 herself and ended up taken by “blue lights,” as she says, to a hospital where she was seriously ill. “That was the last place I wanted to be.”

She notes that while she’s always been passionate about patient care, that experience helped her realize what a huge advantage DCTs are for some people. “Patients really appreciate it. DCT is not going away,” she says.

 

Playbooks, Guidances, and Endpoints
The FDA was quick to release guidances (see below) on how to conduct trials during COVID-19. Proponents of DCTs responded with comments, playbooks, and other documents that helped guide sponsors and others through this unfamiliar terrain.

Below are some of them:

DiMe’s Library of Digital Endpoints:
A crowdsourced library of digital endpoints focused on industry-sponsored studies of new medical products or new applications of existing medical products.

DiMe’s comment in response to the FDA draft guidance on:
Digital Health Technologies for Remote Data Acquisition in Clinical Investigations

DiMe’s Playbook: Digital Clinical Measures

FDA’s draft guidance on Digital Health Technologies for Remote Data Acquisition in Clinical Investigations
Oracle and Informa’s survey on Clinical Trial Management in a Post-Pandemic World
Paraxel’s Discussions on Diversity Report

 

Malorye Branca is a freelenace science writer based in Acton, MA.

The post The Pandemic Supercharged Decentralized Trials, Now What? appeared first on Inside Precision Medicine.

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Breaking the tape

The top performers among drugs launched in 2020 were each the first of their kind.

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Breaking the tape

The top performers among drugs launched in 2020 were each the first of their kind.

By Joshua Slatko • josh.slatko@medadnews.com

The leaders in pharma’s Class of 2020 were all firsts. Veklury, for COVID, and Tepezza, for thyroid eye disease, were each the first drug of any kind to be approved by FDA for their respective disease targets. And while other treatments for migraine exist, Ubrelvy was the first orally administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the treatment of migraine attacks once they start. The era of follow-ons in pharma may not entirely be over; but surely the industry’s researchers are still breaking barriers. 

Earning nearly $5.57 billion in sales during the product’s first full calendar year on the market, Veklury was the first drug approved by FDA for the treatment of COVID-19.

Veklury

The very first drug to be approved in the United States for the treatment of COVID-19, Gilead’s Veklury received emergency use authorization from FDA during May 2020, an expanded EUA three months later, and full approval for treating patients with COVID requiring hospitalization during October 2020. Veklury had originally been developed for the treatment of hepatitis C and had been studied in Ebola and Marburg virus, without success. 

FDA approval was based on three randomized controlled trials including final results of the National Institute of Allergy and Infectious Diseases’ double blind, placebo-controlled Phase III ACTT-1 trial, which showed that treatment with Veklury resulted in clinically meaningful improvements across multiple outcome assessments compared with placebo in hospitalized patients with COVID-19. Based on the strength of these data, Veklury became a standard of care for the treatment of COVID-19 in hospitalized patients.

In the randomized, double-blind, placebo-controlled ACTT-1 trial, Veklury significantly improved time to recovery as compared to placebo – by five days in the overall study population (10 versus 15 days) and seven days in patients who required oxygen support at baseline (11 versus 18 days). As a secondary endpoint, Veklury also reduced disease progression in patients needing oxygen, resulting in a significantly lower incidence of new mechanical ventilation or ECMO (13 percent versus 23 percent). In the overall patient population, there was a trend toward reduced mortality with Veklury compared with placebo at Day 29.

In June 2021, Gilead announced positive data from three retrospective studies of the real-world treatment of patients hospitalized with COVID-19, adding to the body of mortality and hospital discharge data for patients treated with Veklury. All three of the real-world analyses observed that, in the overall patient populations, patients who received Veklury treatment had significantly lower risk for mortality compared with matched controls. A reduction in mortality was observed across a spectrum of baseline oxygen requirements. The results were consistently observed at different time frames over the course of the pandemic and across geographies. Two of the studies also observed that patients who received Veklury had a significantly increased likelihood of discharge from the hospital by Day 28.

In January 2022, FDA granted expedited approval of a supplemental new drug application for Veklury for the treatment of non-hospitalized adult and adolescent patients who are at high risk of progression to severe COVID-19, including hospitalization or death. The expanded indication allowed for Veklury to be administered in qualified outpatient settings that can administer daily intravenous infusions over three consecutive days. FDA also expanded the pediatric EUA of Veklury to include non-hospitalized pediatric patients younger than 12 years of age who are at high risk of disease progression.

These actions by FDA came amidst a surge in COVID-19 cases and the reduced susceptibility to several anti-SARS-CoV-2 monoclonal antibodies (mAbs) due to the Omicron variant. In contrast, Veklury targets the highly conserved viral RNA polymerase, thereby retaining activity against existing SARS-CoV-2 variants of concern. In vitro laboratory testing has shown that Veklury retains activity against the Omicron variant. 

Quarterly sales, VekluryThe FDA sNDA approval, pediatric EUA expansion, and updated National Institutes of Health Treatment Guidelines for COVID-19 that additionally recommend Veklury for treatment in non-hospitalized settings were based on results from the PINETREE Phase III randomized, double-blind, placebo-controlled trial. The study evaluated the efficacy and safety of a three-day course of Veklury for intravenous use for the treatment of COVID-19 in non-hospitalized patients at high risk for disease progression. An analysis of 562 participants randomly assigned in a 1:1 ratio to receive Veklury or placebo, demonstrated that treatment with Veklury resulted in a statistically significant 87 percent reduction in risk for the composite primary endpoint of COVID-19 related hospitalization or all-cause death by Day 28 (0.7 percent, 2/279) compared with placebo (5.3 percent, 15/283). In the study, no deaths were observed in either arm by Day 28.

In February, Gilead released data demonstrating the in vitro activity of Veklury against 10 SARS-CoV-2 variants, including Omicron. Results of Gilead’s studies were consistent with other in vitro studies independently conducted by researchers from institutions in other countries, including Belgium, the Czech Republic, Germany, Poland and the United States, which confirmed Veklury’s antiviral activity against multiple previously identified variants of SARS-CoV-2, including Alpha, Beta, Gamma, Delta and Omicron.

The study analyzed in vitro antiviral activity by two methods to understand the susceptibility of 10 major SARS-CoV-2 variants to Veklury. The study results showed similar activity of Veklury against the variants and an early ancestral A lineage isolate detected in Seattle, Wash. (WA1 strain). Specifically, Delta and Omicron variants both remained fully susceptible to Veklury, and these laboratory results demonstrated that Veklury has remained active against all major variants isolated over the past two years.

In April, FDA approved a supplemental new drug application for Veklury for the treatment of pediatric patients who are older than 28 days, weighing at least 3 kg, and are either hospitalized with COVID-19 or have mild-to-moderate COVID-19 and are considered high risk for progression to severe COVID-19, including hospitalization or death. This approval made Veklury the first and only approved treatment for pediatric COVID patients in the United States. Under the expanded indication, a three-day Veklury treatment regimen is recommended to help prevent hospitalization in non-hospitalized COVID-19 pediatric patients who are at high risk for COVID-19 disease progression. For hospitalized pediatric patients who do not require invasive mechanical ventilation and/or ECMO, a five-day treatment course is recommended. The approval was supported by results from the CARAVAN Phase II/III single arm, open-label study, which demonstrated that Veklury was generally well-tolerated among pediatric patients hospitalized with COVID-19 with a high proportion of participants showing clinical improvement and recovery, as well as data from trials in adults.

Tepezza

Tepezza

Tepezza was the first drug ever approved by FDA for the treatment of thyroid eye disease.

When it earned approval in January 2020, Horizon Therapeutics’ Tepezza became the first and only FDA-approved medicine for thyroid eye disease, a serious, progressive and vision-threatening rare autoimmune disease that is associated with proptosis (eye bulging), diplopia (double vision), blurred vision, pain, inflammation, and facial disfigurement. Tepezza is a fully human monoclonal antibody (mAb) and a targeted inhibitor of the insulin-like growth factor-1 receptor (IGF-1R) that is administered to patients once every three weeks for a total of eight infusions.

The FDA approval of Tepezza was supported by a robust body of clinical evidence, including statistically significant, positive results from the Phase II clinical study, as well as the Phase III confirmatory clinical study OPTIC. The OPTIC study found that significantly more patients treated with Tepezza (82.9 percent) had a meaningful improvement in proptosis (≥ 2 mm) as compared with placebo patients (9.5 percent) without deterioration in the fellow eye at Week 24. Additional secondary endpoints were also met, including a change from baseline of at least one grade in diplopia (double vision) in 67.9 percent of patients receiving Tepezza compared to 28.6 percent of patients receiving placebo at Week 24. In a related analysis of the Phase II and Phase III clinical studies, there were more patients with complete resolution of diplopia among those treated with Tepezza (53 percent) compared with those treated with placebo (25 percent).

In October 2020, Horizon announced new long-term follow-up data from the Phase II clinical trial of Tepezza, which showed a sustained response up to one year following completion of treatment for thyroid eye disease. All patients with Week 72 data (37/37) reported some improvement in at least one of the study outcomes from baseline. 97 percent (36/37) of study participants had an improvement in clinical activity score (decrease of at least 1 point). 86 percent (31/36) had any decrease in proptosis. One patient chose elective TED surgery at Week 70 and did not have proptosis measurements at Week 72. Of patients with baseline diplopia, 70 percent (23/33) had an improvement of at least one grade. 70 percent (26/37) had disease inactivation (CAS of 0 or 1 point).

During December 2020, Horizon announced that the company expected a short-term disruption in Tepezza supply as a result of government-mandated COVID-19 vaccine production orders related to Operation Warp Speed that dramatically restricted capacity available for the production of Tepezza at its drug product contract manufacturer, Catalent. In March 2021, FDA cleared a prior approval supplement to the previously approved Biologics Licensing Application giving Horizon authorization to manufacture more Tepezza drug product resulting in an increased number of vials with each manufacturing slot. The company began to resupply the market in April, which ended the supply disruption.

Tepezza Quarterly SalesIn April 2021, new pooled data from the Tepezza Phase II and III trials was published in The Lancet Diabetes & Endocrinology. This data further reinforced that Tepezza significantly improves proptosis and diplopia for TED patients in different subgroups, with most maintaining a long-term response. There was no evidence for acute disease rebound (increase in percentage of patients no longer meeting proptosis, diplopia or ophthalmic composite outcome) seven weeks after the last dose of Tepezza. Proptosis (87 percent; 62/71), diplopia (66 percent; 38/58) and ophthalmic composite outcome (92 percent; 66/72) responses were observed seven weeks after the last dose of Tepezza. A post-hoc analysis of the composite ophthalmic outcome indicated that 81 percent (68/84) of Tepezza patients versus 44 percent (38/87) of placebo patients were responders at Week 24. Proptosis (67 percent; 38/57), diplopia (69 percent; 33/48) and composite outcome response (83 percent; 48/58) were observed 51 weeks after the last dose of Tepezza for those who had long-term off-treatment data available.

Additionally, in a post-hoc analysis, Tepezza-treated patients with more severe disease (those with ≥3 mm of proptosis and/or inconstant or constant diplopia) and those with less severe disease at baseline both experienced significant improvements in proptosis and diplopia. In patients with more severe disease, those treated with Tepezza had a proptosis response of 79 percent (50/63) compared to 17 percent (11/65) of those who received placebo, and a diplopia response of 68 percent (38/56) compared to 31 percent of those who received placebo (15/49). In patients with less severe disease, those treated with Tepezza had a proptosis response of 71 percent (15/21) compared to 9 percent in those who received placebo (2/22), and a diplopia response of 80 percent (8/10) compared to 30 percent in placebo (3/10).

In post-hoc analyses, patients who received Tepezza in both the lower baseline CAS subgroup (4 or 5) and the higher CAS subgroup (6 or 7) demonstrated statistically significant improvements compared with placebo in proptosis and diplopia. Overall response and CAS of 0 or 1 response also improved.

Post-hoc analysis from the Phase III study also demonstrated that in patients treated with Tepezza, those with higher (≥10 IU/L) or lower (<10 IU/L) serum thyrotropin-binding inhibitory immunoglobulin (TBII) baseline levels both had a proptosis response (mean reduction of -3.65 mm and -3.01 mm, respectively) with no treatment difference between the two groups. In patients with higher baseline TBII, 71 percent (10/14) of patients who received Tepezza experienced an improvement in diplopia compared to 23 percent (3/13) of patients who received placebo.

In November 2021, Horizon announced findings of a real-world adherence analysis of Tepezza for the treatment of TED. The analysis found that more than 90 percent (n=995) of people who were prescribed Tepezza for TED went on to complete all eight infusions, indicating a high level of adherence to the medicine in clinical practice. The study evaluated 1,101 people living with TED (71 percent female, mean age 58 years) who started treatment with Tepezza prior to July 2020. Non-compliance was low at approximately 1 percent (n=15). Only 8 percent (n=84) reported that they discontinued because of adverse events.

In June 2022, Horizon announced results of a new analysis examining rates of hyperglycemia among patients treated with Tepezza for TED compared to placebo in the Phase II and OPTIC Phase III clinical trials. The analysis found a total of nine adverse event reports of hyperglycemia in eight patients (8/84, 10 percent) who received Tepezza, and one patient (1/86; 1.2 percent) who received placebo. The majority (5/8, 63 percent) of patients who experienced hyperglycemia while taking Tepezza had pre-existing diabetes. Of the hyperglycemic AEs reported in the Tepezza-treated patients, all were controlled with medicine. All reported AEs were grade 1 (>ULN-160mg/dl) or grade 2 (161 – 250mg/dl), and none led to study discontinuation. HbA1c levels increased by 0.22 percent in those treated with Tepezza compared to 0.04 percent among placebo patients.

Ubrelvy

Ubrelvy

Ubrelvy was the first orally administered calcitonin gene-related peptide receptor antagonist (gepant) to be approved by FDA for the treatment of migraine attacks once they start.

Approved by FDA in late December of 2019, Ubrelvy was the first orally administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the treatment of migraine attacks once they start. Ubrelvy works by blocking CGRP, a protein that is released during a migraine attack, from binding to its receptors. It works without constricting blood vessels, which some older treatments were known to do. FDA’s approval was based on four clinical studies (ACHIEVE I, ACHIEVE II, UBR-MD-04, and 3110-105-002), which demonstrated efficacy, safety, and tolerability of orally administered Ubrelvy in the acute treatment of migraine. Both 50 mg and100 mg dose strengths demonstrated significantly greater rates of pain freedom and freedom from the most bothersome migraine-associated symptom at two hours, compared with placebo. Ubrelvy joined AbbVie’s portfolio when that company completed its acquisition of Allergan in May 2020. 

In August 2020, AbbVie announced Serena Williams as the spokesperson for Ubrelvy to raise awareness of an effective acute treatment option for people living with migraine. The multichannel marketing campaign featuring Williams highlighted how Ubrelvy works for people with different lifestyles by helping individuals treat their migraine attacks anytime, anywhere. As spokesperson, she was featured in a video, available on social media, talking with neurologist and paid AbbVie consultant Dr. Jennifer McVige about her experience with migraine and Ubrelvy. Williams was also included in print and digital advertising and other marketing initiatives.

In September 2021, FDA approved Abb­Vie’s Qulipta, another drug from the gepant family, for the preventive treatment of episodic migraine in adults. Qulipta is the first and only oral calcitonin gene-related peptide receptor antagonist specifically developed for the preventive treatment of migraine. The approval was supported by data from a robust clinical program evaluating the efficacy, safety, and tolerability of Qulipta in nearly 2,000 patients who experienced 4 to 14 migraine days per month, including the pivotal Phase III ADVANCE study, the pivotal Phase IIb/III trial, and the Phase III long-term safety study.

Ubrevly quarterly salesIn the pivotal Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group ADVANCE trial, the primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period. All Qulipta dose groups met the primary endpoint and demonstrated statistically significant reductions in mean monthly migraine days compared to placebo. Patients treated with 60 mg of Qulipta across 12 weeks experienced a 4.2-day reduction from baseline of 7.8. A key secondary endpoint in the ADVANCE trial measured the proportion of patients that achieved a ≥50 percent reduction in monthly migraine days across the 12-week treatment period. The trial demonstrated that 56 percent/59 percent/61 percent of patients in the 10 mg/30 mg/60 mg Qulipta arms, respectively, achieved a 50-100 percent reduction, compared to 29 percent of patients in the placebo arm.

During June, AbbVie submitted a supplemental NDA to FDA for Qulipta to support the preventive treatment of chronic migraine in adults. If approved, Qulipta would be the first gepant cleared for the broad indication of the preventive treatment of migraine, including episodic and chronic. The supplemental NDA submission includes data from the pivotal Phase III PROGRESS trial in patients with chronic migraine, which supplements the existing data in episodic migraine. People living with chronic migraine experience headaches for 15 or more days per month, which, on at least eight of those days per month, have the features of migraine.

The Phase III PROGRESS trial met its primary endpoint of statistically significant reduction from baseline in mean monthly migraine days compared to placebo across the 12-week treatment period in adults with chronic migraine. The trial also demonstrated that treatment with Qulipta 60 mg once daily (QD) and 30 mg daily (BID) resulted in statistically significant improvements in all six secondary endpoints. This includes a key secondary endpoint that measured the proportion of patients that achieved at least a 50 percent reduction in mean monthly migraine days across the 12-week treatment period. 

Josh Slatko, Med Ad News Josh Slatko is contributing editor of Med Ad News and PharmaLive.com.

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Over the top

The biopharma industry’s response to the global pandemic has propelled some COVID-19 vaccines into the leading ranks of the world’s best-selling products,…

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Over the top

The biopharma industry’s response to the global pandemic has propelled some COVID-19 vaccines into the leading ranks of the world’s best-selling products, with Pfizer/BioNTech’s Comirnaty surpassing AbbVie’s Humira for the No. 1 spot.

By Andrew Humphreys • andrew.humphreys@medadnews.com

The ripple effects of the worldwide COVID-19 pandemic continue to be felt throughout the biopharmaceutical realm, from allocation of business resources to the revenue impact of new vaccines and treatments for the industry’s main players. No biopharma company has thrived more during the pandemic’s reign than Pfizer, which experienced the largest increase in market capitalization during 2021 at $127 billion, rising to $331 billion. 

Comirnaty became the first COVID-19 vaccine to gain full approval.

Pfizer has collaborated with BioNTech to jointly develop the mRNA-based coronavirus vaccine Comirnaty/BNT162b2 to help prevent COVID-19. Comirnaty/BNT162b2 accounted for 45 percent of Pfizer’s total revenue during 2021, coming in at $36.78 billion. For the first six months of 2022, Pfizer reported Comirnaty direct sales and alliance revenue of $22.08 billion. As of July 28, Pfizer forecasted $32 billion in revenue for Comirnaty for full-year 2022, with gross profit to be split evenly with BioNTech, which includes doses expected to be delivered throughout the fiscal year. 

Comirnaty is based on Bi­oN­Tech’s proprietary messenger RNA technology. As the first-ever approved mRNA therapy, Comirnaty additionally represents BioNTech’s first commercial product. Through the vaccine, BioNTech’s revenue grew from €482.3 million ($571 million) in 2020 to €18.98 billion ($22.45 billion) for 2021. In reporting first-quarter 2022 results, BioNTech reiterated the company’s prior full-year 2022 financial year outlook of €13 billion ($15.4 billion) to €17 billion ($20.11 billion).

Pfizer-BioNTech’s COVID-19 vaccine is authorized by the U.S. Food and Drug Administration under Emergency Use Authorization (EUA) for active immunization to prevent coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 6 months of age and older. Comirnaty (approved under a Biologics License Application)/BNT162b2 (authorized under EUA) in July 2022 became the first COVID-19 vaccine to be granted FDA approval for adolescents 12 years and older, following U.S. emergency use authorization in May 2021. Comirnaty became the first FDA-approved COVID-19 vaccine for individuals 16 years and older during August 2021. 

The impact of the worldwide pandemic led to the unseating of Humira (adalimumab) as the world’s top-selling pharmaceutical product in 2021, which was the medicine’s best-performing year ever. Humira has annually been the best seller among prescription medicines dating back to 2012. The drug’s combined revenue for 2021 between AbbVie and Japan’s Eisai topped $21.18 billion. AbbVie reported $20.69 billion of that total, the first time Humira broke the $20 billion barrier in one year for the North Chicago-based company. For first-half 2022, AbbVie reported Humira worldwide revenue of $10.1 billion.Humira

Humira is administered as a subcutaneous injection. The biologic therapy is approved for treating various autoimmune diseases in North America and in the European Union: rheumatoid arthritis (moderate to severe), psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease (moderate to severe), plaque psoriasis (moderate to severe chronic), juvenile idiopathic arthritis (moderate to severe polyarticular), ulcerative colitis (moderate to severe), axial spondyloarthropathy, pediatric Crohn’s disease (moderate to severe), hidradenitis suppurativa (moderate to severe), pediatric enthesitis-related arthritis, non-infectious intermediate, posterior and panuveitis, pediatric ulcerative colitis (moderate to severe), and pediatric uveitis. Humira is approved in Japan for treating intestinal Behçet’s disease and pyoderma gangrenosum.

Humira is sold in other markets around the globe, including Japan, China, Brazil, and Australia. The medication accounted for 37 percent of AbbVie’s total net revenue during 2021 and nearly 36 percent during the first six months of 2022.

Moderna’s COVID-19 vaccine Spikevax (mRNA-1273) has been authorized for use or approved in more than 70 countries. The FDA fully approved the BLA for Spikevax for individuals 18 years of age and older in January 2022. Moderna’s COVID-19 vaccine was made available under EUA in the United States on Dec. 18, 2020. The full licensure of Spikevax in the United States joined that in Canada, Japan, the European Union, the UK, Israel, and other countries where the adolescent indication is additionally approved. 

During June 2022, Moderna gained EUA from the FDA for the company’s COVID-19 vaccine mRNA-1273 in young children ages 6 months through 5 years of age at a dose level of 25 µg. Moderna has additionally received emergency use authorization for a 50 µg two-dose regimen of mRNA-1273 for children ages 6 through 11 years old and a 100 µg two-dose regimen for adolescents aged 12 through 17 years old. 

Spikevax marks Moderna’s first commercial product. Sales amounted to nearly $17.68 billion during full-year 2021. For the first six months of 2022, Moderna reported product sales of about $10.46 billion.

Keytruda ranks as the world’s top-selling cancer therapeutic. Global sales for Merck’s checkpoint inhibitor grew from $11.08 billion during 2019 to $14.38 billion for 2020 and $17.19 billion in 2021. For first-half 2022, Merck reported Keytruda global sales of $10.06 billion. The anti-PD-1 (programmed death receptor-1) therapy contains the active chemical pembrolizumab.

Keytruda

Keytruda works by increasing the ability of the body’s immune system to help detect and fight tumor cells. The humanized monoclonal antibody blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes that may affect both tumor cells and healthy cells.

Outside the COVID-19 vaccine domain, Keytruda is expected to overtake Humira as the top-selling prescription medicine in 2023 when the latter’s U.S. market exclusivity is set to expire. AbbVie has entered into settlement and license deals with several adalimumab biosimilar manufacturers. The licenses in the United States will start during 2023 and the licenses in Europe began in 2018. “The inevitable arrival of Humira biosimilars in the U.S. next year means that AbbVie is hurtling towards biopharma’s biggest-ever patent cliff,” according to Evaluate Pharma analysis.

Meanwhile, Keytruda is anticipated to continue thriving as the product’s compound patent is protected from expiration in all majors markets until at least 2028 (the United States and China) and into the following decade in the EU and Japan. 

According to analysts from Evaluate Pharma, come 2028, Keytruda will remain the top-selling non-Covid treatment with estimated sales of $30.9 billion. By that year, the top-selling pharmaceutical of all-time, Humira, will no longer be a member of the top 10 sellers (see graphic on this page). 

Per Evaluate Pharma, the No. 2 seller in 2028 is projected to be Bristol Myers Squibb and Ono Pharmaceutical’s Opdivo (nivolumab), predicted to trail Keytruda by nearly half in revenue at $15.7 billion. A fully human monoclonal antibody that binds to the PD-1 on T and NKT cells, the biological product Opdivo has received approvals for various anti-cancer indications including bladder, blood, colon, head and neck, kidney, liver, lung, melanoma, mesothelioma and stomach.

Biggest Selling Drugs, Evaluate Pharma

Download the listing of the top 200 medicines based on global sales during 2021

Andrew Humphreys is contributing editor of Med Ad News and PharmaLive.com.

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Braxia and KetaMD, CEOs McIntyre and Gumpel Speak on Acquisition

Last week, the Canadian company Braxia Scientific acquired 100% of the issued and outstanding stock of KetaMD, Inc. This is an exciting acquisition, and…

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Last week, the Canadian company Braxia Scientific acquired 100% of the issued and outstanding stock of KetaMD, Inc. This is an exciting acquisition, and in today’s interview, The Dales Report’s Nicole Hodges talks with CEOs Dr. Roger McIntyre and Warren Gumpel of Braxia Scientific and KetaMD respectively.

For some background information, KetaMD is a U.S. based, privately-held, innovative telemedicine company, with a mission to address mental health challenges via access to technology-facilitated ketamine-based treatments. Braxia Scientific is Canada’s first clinic specializing in ketamine treatments for mood disorders. They recorded revenue of $1.49m for 2022 fiscal year, ended March 31. On a year-over-year basis, revenue increased 47.5%.

Here’s some highlights from the interview.

KetaMD gives Braxia a presence in the US

Dr. McIntyre says that KetaMD gives Braxia what they’ve had as their vision from the beginning: a US presence. KetaMD is a living program. It’s already running, has infrastructure, and patients. McIntyre believes that a program like KetaMD is something Braxia’s needed to scale and obtain commercial success.

With telemedicine, Braxia has a potential to serve a gap in access. The zeitgeist of “patient going to medicine” has flipped, McIntyre says. “Now it’s medicine goes to the patient, and that is long overdue.”

COVID speeding a trend that was already happening

In 2020, 80% of physicians indicated they had virtual visits. That’s a number up from 22% the year before. But this is something that many doctors, McIntyre included, believe always should have happened. The pandemic only was the catalyst for innovation and making the option viable.

While some treatments will always need a clinic or a hospital, McIntyre believes some treatments can be done safely at home. And they are, for many chronic diseases. He feels implementing ketamine and psychedelics would be among these treatments where service could be expanded into the home. It would require careful SOPs in place, best practices, and surveillance. But he believes Braxia Scientific could deliver this with KetaMD.

Gumpel to stay as CEO of KetaMD

Gumpel says that KetaMD benefits in this acquisition from being part of the world’s most prominent researchers in depression, psychedelics, and ketamine. In the acquisition, he’ll stay on as CEO. He admits that Dr. McIntyre has been a huge part of collecting the data on the safety of ketamine treatment, and has a strong motivation to “see this thing through until most of society can access that – or at least the people that need it and want it.”

Gumpel admits he has a personal connection to ketamine treatment. As a person who has experienced bouts of depression for years, it saved his life, he says. He is grateful he was living within walking distance of ketamine treatment in Manhattan. It made him extremely aware of the accessibility gap, which in part inspired KetaMD.

Be sure to tune in for the full interview regarding Braxia and KetaMD, right here on The Dales Report!

The post Braxia and KetaMD, CEOs McIntyre and Gumpel Speak on Acquisition appeared first on The Dales Report.

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