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Roche nabs a priority review for Evrysdi, hoping to become the first oral treatment for infants with SMA

Roche has been duking it out with Biogen and Novartis ever since bursting into the spinal muscular atrophy space about a year and a half ago with its competitively priced oral treatment Evrysdi. Now the pharma giant is looking to stake its claim in a…

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Roche has been duking it out with Biogen and Novartis ever since bursting into the spinal muscular atrophy space about a year and a half ago with its competitively priced oral treatment Evrysdi. Now the pharma giant is looking to stake its claim in a younger subset of patients — and the FDA has agreed to give it a speedy review.

Regulators have granted priority review to a supplemental NDA for Evrysdi (risdiplam) to treat pre-symptomatic babies under 2 months old with SMA. While the drug is currently approved for adults, children and babies older than 2 months, a new approval here would make it the first at-home treatment available for younger infants. A decision is expected by May 30, according to Roche.

“Treating very young babies with Evrysdi before SMA symptoms arise may help them to achieve milestones such as standing and walking within timeframes typical of healthy infants,” CMO Levi Garraway said in a statement.

Evrysdi — licensed by Roche from PTC Therapeutics — is designed to treat SMA by modifying how the SMN2 gene is spliced, thus increasing functional SMN protein levels in both the central nervous system and peripheral tissues. SMN protein is critical for maintaining healthy motor neurons and movement.

The drug got a quick OK back in 2020, becoming the first oral treatment for SMA. Analysts penciled in a peak sales estimate of around $2 billion. Its competitors, Biogen’s Spinraza and Novartis’ Zolgensma, are administered by injection to the spinal cord and IV infusion, respectively.

Matthew Klein

“I think that that’s really important. One, just in general, saving people the inconvenience of going to a hospital. I think most people would much rather take something by mouth than have a procedure done, and probably even more important in COVID,” PTC COO Matthew Klein told Endpoints News. “I think people are really not wanting to… leave home, let alone go to medical facilities.”

At an interim analysis in the RAINBOWFISH study, all five patients under 2 months old maintained the ability to swallow and were able to feed exclusively by mouth after 12 months of treatment, according to Roche. Four of those five patients achieved milestones such as standing and walking independently, and all met the HINE-2 motor milestones of head control, sitting upright, rolling and crawling after 12 months.

The drug appeared safe, with no treatment-related serious events reported in any of the babies. Four treatment-emergent side effects were reported out of 12 babies, all of which were resolved or resolving with ongoing Evrysdi treatment. The most common side effects were nasal congestion (33%), cough (25%), teething (25%), vomiting (25%), eczema (17%), abdominal pain (17%), diarrhea (17%), gastroenteritis (17%), papule (17%) and pyrexia (17%).

“The AEs were reflective of the age of the babies rather than the underlying SMA,” Roche said.

From the start, Roche promised to “underwhelm” with Evrysdi’s price compared to competitors. The pharma giant set the price on a scale based on a child’s weight, maxing out when they reach 44 lbs at about 6 years of age. For example, for an infant who weighs 15 lbs and is less than 2 years old, the annual price of Evrysdi would be less than $100,000, a spokesperson told Endpoints.

Meanwhile, Zolgensma has earned the notorious title of the most expensive drug in the world at $2.1 million per patient, and back in 2020, Spinraza cost between $625,000 and $750,000 for the first year and around $375,000 every year after.

Evrysdi’s lower price hasn’t stopped it from reeling in mammoth sales. In Q3 of 2021, the drug netted around $429 million, compared to Zolgensma’s $375 million and Spinraza’s $$444 million. Spinraza’s Q3 sales decreased from $494 million in Q3 of 2020, which Biogen attributed to growing competition and the impacts of Covid-19.

Roche shelled out $30 million upfront for the rights to Evrysdi back in 2011, promising up to $460 million in biobucks and up to double-digit royalties on commercial sales. PTC raked in $35 million in milestone payments in Q3 of 2020 and $7.5 million in Q4, according to the company’s year-end report. The drug is currently approved in 70 countries and has been submitted for approval in 31 more.

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US Allows 2 Million Baby Formula Cans In From UK, Lets Abbott Release 300,000 Specialty Cans

US Allows 2 Million Baby Formula Cans In From UK, Lets Abbott Release 300,000 Specialty Cans

Authored by Mimi Nguyen Ly via The Epoch Times…

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US Allows 2 Million Baby Formula Cans In From UK, Lets Abbott Release 300,000 Specialty Cans

Authored by Mimi Nguyen Ly via The Epoch Times (emphasis ours),

The U.S. Food and Drug Administration (FDA) announced on Tuesday it will allow about 2 million cans of baby formula from the United Kingdom into the country, and allow Abbott Laboratories to release about 300,000 cans of specialty formula, to help ease the ongoing nationwide shortage.

“We continue to do everything in our power as part of the all-of-government efforts to ensure there’s adequate infant formula available wherever and whenever parents and caregivers need it,” FDA Commissioner Robert Califf said in a statement. “Our recent steps will help further bolster supply of infant formula, including through the import of safe and nutritious products from overseas based on our increased flexibilities announced last week.

Importantly, we anticipate additional infant formula products may be safely and quickly imported into the U.S. in the near-term based on ongoing discussions with manufacturers and suppliers worldwide.”

Shelves are empty of baby formula at a store in Chelsea, Massachusetts, on May 20, 2022. (Joseph PreziosoAFP via Getty Images)

The FDA announced it is “exercising enforcement discretion” to allow the importation of the 2 million cans from UK-based company Kendal Nutricare. The cans, which are under the company’s Kendamil brand, have no safety or nutrition concerns after an evaluation, and are expected to land on U.S. store shelves starting in June, the FDA said.

Kendal Nutricare currently has over 40,000 cans in stock for immediate dispatch, the agency said, adding that the U.S. Department of Health and Human Services is discussing options to get those cans into the country as soon as possible.

The FDA also announced it is letting Abbott release some 300,000 cans of its EleCare amino acid-based formula for babies and infants who urgently need it to survive, on a case-by-case basis.

The cans of specialty formula were previously produced at Abbott’s facility in Sturgis, Michigan, where other baby formula products that were recalled by Abbott on Feb. 17 were produced.

These products will undergo enhanced microbiological testing before release. Although some EleCare product was included in Abbott Nutrition’s infant formula recall, these EleCare products that will be released were in different lots, have never been released and have been maintained in storage under control by Abbott Nutrition,” the FDA noted.

“Given the critical need of this product for some individuals, the FDA encourages parents and caregivers to consult with their health care providers to weigh the potential risk of bacterial infection with this product,” it added. “Parents and caregivers seeking access to these products should contact Abbott directly to request that a product be made available to them by calling 1-800-881-0876.”

The ongoing baby formula shortage in the United States was recently exacerbated after Abbott Laboratories, the biggest U.S. supplier of powder baby formula, in February recalled some products, including those under the brand Similac, and temporarily shuttered its manufacturing facility in Sturgis, Michigan, which was producing up to one-quarter of the country’s baby formula.

The recall came after reports of bacterial infections among four infants, two of whom died. The FDA, which launched an investigation into the matter following consumer complaints, cannot conclude whether the cases of infants that fell sick were directly related to the Abbott facility until its investigation is concluded, Califf previously said.

Production at the Sturgis facility is set to restart on June 4, Abbott said in a statement. The company said it would prioritize making EleCare and supplying it on or about June 20. It also the formula would be provided to children in need for free.

Prior to the Abbott recall, the baby formula shortage among multiple manufacturers was brought on by supply chain pressures linked to COVID-19 pandemic lockdowns.

Also on Tuesday, the Federal Trade Commission launched an inquiry into the ongoing shortage of baby formula in the country, calling for public input on the matter.

The Biden administration has sought to relieve the shortage by importing emergency supplies from Europe via Defense Department-contracted commercial aircraft under “Operation Fly Formula.” The first lots of formula arrived in Indianapolis, Indiana, from Germany on Sunday.

President Joe Biden has also invoked the Cold War-era Defense Production Act to help manufacturers obtain ingredients to produce more formula.

Tyler Durden Thu, 05/26/2022 - 07:20

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Updated: US sees spike in Paxlovid usage as Merck’s molnupiravir and AstraZeneca’s Evusheld are slower off the shelf

New data from HHS show that more than 162,000 courses of Pfizer’s Covid-19 antiviral Paxlovid were administered across the US over the past week, continuing…

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New data from HHS show that more than 162,000 courses of Pfizer’s Covid-19 antiviral Paxlovid were administered across the US over the past week, continuing a streak of increased usage of the pill, and signaling not only rising case numbers but more awareness of how to access it.

In comparison to this week, about 670,000 courses of the Pfizer pill have been administered across the first five months since Paxlovid has been on the US market, averaging about 33,000 courses administered per week in that time.

A Pfizer spokesperson told Endpoints News the company does “not have any concerns nor foresee any supply issues in our ability to support if [usage] rates increase.”

Cumulatively, as of May 24, almost 3.8 million doses of Paxlovid have been made available to states so far by the federal government, and about 2.4 million of those have been ordered by states, with more than 831,000 courses administered.

Signs for such a spike in usage were evident earlier this month, as in a call with reporters senior HHS officials credited the surge in the use of Paxlovid to their outreach, and through the Biden administration’s Test to Treat initiative, which allows for use of Paxlovid with a positive test at participating pharmacies.

“We have seen more than a 315% increase in Paxlovid use over the past four weeks. In the first week of May, nearly 115,000 courses were dispensed,” an official said at the time.

Meanwhile, outside of Paxlovid, few other treatment options are really in wide use.

Merck’s molnupiravir, known commercially as Lagevrio, has struggled to make its way out of the inventory closet, according to the latest numbers posted by HHS.

Only about 20,000 courses of the Merck pill were used in the past week, and only about 13% of the total US inventory of molnupiravir has been used to date. That compares with about 35% of overall usage of Paxlovid courses ordered by states so far, and the bulk of those orders have come within the last several months.

But for AstraZeneca’s preexposure mAb Evusheld, only about 16,000 courses were administered in the past week. About 38% of all Evusheld ordered by states has been administered so far, according to the latest HHS numbers.

For Eli Lilly’s bebtelovimab, which is a monoclonal antibody that’s supposed to be used ahead of molnupiravir if both are on hand, about 100,000 courses in total have been administered of 379,526 courses ordered (542,330 courses available). Bebtelovimab is the follow-on mAb after Lilly’s former combo mAb (850,000+ courses distributed earlier in the pandemic) that lost efficacy against the latest variant.

Meanwhile, HHS has become less and less transparent with its data and information on its distribution of Covid-19 therapeutics.

After the Trump administration, and the beginning of the Biden administration allowed for the public posting of weekly calls between HHS and states on Covid-19 therapeutic distribution, those calls have since been made private and the prior recordings have been deleted from the ASPR website.

In addition, each week’s therapeutic administration numbers have to be tallied independently because HHS now deletes the previous week’s numbers.

Editor’s note: Article updated to add Pfizer comment and note the stats for Lilly’s Covid-19 treatments bebtelovimab too.

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Why are clinical trials struggling with diversity?

In the diverse world we live in, the products we produce, the services we create and the places
The post Why are clinical trials struggling with diversity?…

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In the diverse world we live in, the products we produce, the services we create and the places we work should be as equally representative. In recent years this has seen diversity, equity, and inclusion (DEI) become a big focus for industries to get right.

Within pharma and healthcare, where greater representation has been proven to lead to better health outcomes for all patients and the pharmaceutical companies developing medicines, change is also happening.

Fair and timely access to efficacious medicine is one of the vital tenets of the healthcare industry and is a critical building block of the sector’s environmental, social and governance (ESG) objectives. But historically there are groups that are typically neglected due to the current systems in place. Racial disparities are still commonplace in many clinical trials with white-ethnic groups often overrepresented amongst trial participants.

Factors such as ethnicity, gender, sexual orientation and age can contribute to interindividual differences in treatment responses and risks of adverse events. Inadequate clinical trial representations of all populations can therefore leave underrepresented groups vulnerable due to the lack of subgroup-specific data.

While many pharma companies are actively working on initiatives to improve diversity in clinical trials, we still have a long way to go. The good news is that technology is being harnessed to promote a DEI-conscious agenda within the clinical trial space, making diversity more attainable than it ever has been.

To understand why improving diversity, mitigating bias, and reinforcing inclusion in clinical trials is such a big task, it’s important to understand the challenges currently at play.

Unpacking the status quo

Traditional Randomised Control Trials (RCTs) continue to form the backbone of clinical efficacy and safety data submitted to health authorities for regulatory review. A risk-benefit approach underpins the decision-making process to evaluate human drugs, drug/device combinations and advanced therapy medicinal products for licensing of human medicines.

It is well-established that safety and efficacy data is highly influenced by internal (intrinsic: ethnicity, sex, age, genetic background) and external (extrinsic: climate, education, access to healthcare) factors. The challenge for regulators and pharma companies is that safety and efficacy data from an RCT may not always translate to the real world ‘effectiveness’ of a medicine (how efficacious the drug is in patients once marketed) which is governed by these complex intrinsic and extrinsic factors.

To mitigate against potentially lower drug efficacy or a different drug safety profile in a wider population vs those findings evidenced in RCTs it is important for companies to include ‘patient-orientated’ outcomes (relief of symptoms) alongside traditional endpoints (blood pressure, glucose concentrations). The diversity of clinical trial patients in the context of disease prevalence is key to capturing ‘patient-orientated’ outcomes in populations. For example, with skin conditions, textbooks, studies, and trial photos often present lighter-skinned individuals’ symptoms, which are bound to differ in darker skinned individuals.

The pandemic brought imbalances into sharp focus

The race to produce a vaccine which could protect the world against COVID-19 brought the topic of diversity in clinical trials, or lack of it, into sharp focus.

Vaccines approved for public use require comprehensive RCTs to establish their safety and efficacy. The demographics of vaccine trial participants should reflect the vulnerable groups to whom infection with the disease presents the greatest risk of harm and mortality. However, this did not happen to the extent it could have during trials for the COVID-19 vaccine.

Research has shown a disproportionately higher rate of COVID-19 infection and mortality among the elderly and minority ethnic groups who are more likely to be negatively impacted by social and economic deprivation linked to pre-existing health conditions. In the UK, during the first wave of the COVID-19 pandemic, ethnic minority groups (except for women in “Chinese” or “White Other” categories) had higher rates of death post-exposure compared with the “White British” population.

These issues are not confined to the UK; in the US, some minority groups including Black, Latino, Pacific Islander and Indigenous peoples have been shown to have twice the COVID mortality rate of Caucasian people.

Despite policies, guidelines, and regulations to promote the diversification of clinical trial groups by the European Medicines Agency (EMA) and FDA, the inclusion of key demographic populations within clinical research continues to be less than proportionate to their representation in society.

Why are certain ethnic groups underrepresented?

Redressing the imbalance in trial participation is not a simple task. Throughout the pandemic, the issue of vaccine hesitancy was compounded by ethnic disparities. This is underpinned by historical mistrust in healthcare organisations, governments, and clinical research, which is still prevalent in some communities.

Factors influencing trust vary between ethnic groups. Reported experiences of discrimination, perceived structural inequalities impacting the access to and quality of healthcare, and concerns of trial under-representation are likely to influence trust issues, of which the latter is within the remit of companies to acknowledge and address with appropriate measures to effect change. Without diverse participation in clinical research there is a lack of breadth in safety and efficacy data. Certain groups of individuals may then not trust that the medicines have been produced with them in mind and may be highly sceptical of the resulting evidence base and prescribing label of medicines.

In the second half of this article, we’ll look at how technology is being used to make clinical trials more diverse and consider some of the lessons learned during the COVID-19 pandemic.

About the authors

Tanya Chambers is an ex-MHRA (Medicine and Healthcare Regulatory Agency) Senior Assessor with over 15 years’ experience principally evaluating preclinical data packages (small molecules and biologics) accompanying clinical trial applications, EU & UK marketing authorization applications (MRP/DCP/Centralised submissions) and variations across all therapeutic areas. Most recently, Tanya led the preclinical rolling review for COVID anti-viral applications resulting in national roll-out, and was product lead for the review of a vast array of development programmes via UK innovative licensing pathways: iLAP and EAMs. In addition, Tanya has working knowledge of the collaborative review of promising oncology treatments alongside Australia (TGA), Canada (Health Canada), UK (MHRA), Singapore (HSA), Switzerland (Swissmedic) and Brazil (ANVISA): ‘Project ORBIS’.

Liam Johnstone has six years of toxicology experience working across regulators in the UK, developing expertise in medicine, consumer product and agrochemical safety whilst working at the MHRA, OPSS and HSE, respectively. As a Non-Clinical Assessor at MHRA he assessed non-clinical data packages for new and generic medicines. He has provided scientific advice to companies both nationally and as part of the Scientific Advice Working Party (SAWP) on the suitability of non-clinical data packages and study plans, as well as generating guidance for the European Medicines Agency (EMA)

 

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