Andy Studna

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Prilenia Therapeutics B.V. has announced it will present clinical data supporting a future Phase III study of the investigational therapy pridopidine for amyotrophic lateral sclerosis (ALS). Prilenia, a clinical stage biotechnology company that develops treatments for neurodegenerative diseases and neurodevelopmental disorders, plans to present the data during the 14th Annual California ALS Research Summit in Los Angeles.

The future Phase III study will examine the effectiveness of pridopidine for ALS and is slated to start in the second half of 2024. According to a company press release from Prilenia, “Pridopidine is an investigational oral, small molecule, highly selective and potent Sigma-1 Receptor (S1R) agonist being studied as a potential treatment for ALS and Huntington’s disease (HD). The S1R is highly expressed in the brainstem and spinal cord, areas implicated in ALS and important for bulbar function and speech.”

According to an estimate from the Centers for Disease Control and Prevention, there are over 31,000 patients living with ALS in the United States as of 2017. On average 5,000 new patients are diagnosed with ALS every year.

“Based on the clinical data generated to date, pridopidine has the potential to become a meaningful treatment for ALS, slowing key measures of disease progression, including function, respiration, quality of life and impact on speech, which is very meaningful for patients and caregivers, as well as prolonging overall survival,” said Michael R. Hayden, PhD, CEO and founder of Prilenia, in a press release. “We believe it is important for Prilenia to advance our clinical program in ALS, and we are actively planning a single, global, pivotal Phase 3 clinical trial. Our sincere appreciation to the many ALS patients, caregivers and healthcare providers who have contributed so much to our clinical studies as well as to those who will participate in future trials. We also are grateful to Dr. Merit Cudkowicz and the entire team at the Sean M. Healey & AMG Center for ALS for their innovative and passionate approach to evaluating pridopidine as we continue our close working relationship.”

According to the press release, pridopidine did not meet the primary outcome measure in an earlier Phase II study, the HEALEY ALS Platform Trial. However, there were data from the pre-specified subgroup that showed promising results with slower disease progression among participants with definite ALS who were also early in the course of the disease (less than 18 months from symptom onset).

“In the Phase II clinical trial, pridopidine showed encouraging results for the potential treatment of ALS across multiple secondary and exploratory measures with an excellent safety profile, and we are pleased to work closely with Prilenia on the advancement of this program into Phase III,” said Merit Cudkowicz, MD, MSc, principal investigator, and sponsor of the HEALEY ALS Platform Trial, Director of the Sean M. Healey & AMG Center for ALS, Chair of the Department of Neurology at Massachusetts General Hospital, and the Julieanne Dorn Professor of Neurology at Harvard Medical School said in a press release.

Prilenia Announces Clinical Data in Support of its Plans to Initiate Global Phase 3 Study in ALS. Prilenia Therapeutics B.V. News release. January 19, 2024. Accessed January 23, 2024. 

https://news.prilenia.com/press-releases/press-release-details/2024/Prilenia-Announces-Clinical-Data-in-Support-of-its-Plans-to-Initiate-Global-Phase-3-Study-in-ALS/default.aspx

Amyotrophic lateral sclerosis. Centers for Disease Control and Prevention, U.S. Department of Health & Human Services. Accessed January 23, 2024. 

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Data from prior Phase II study showed signs of pridopidine slowing disease progression in patients with amyotrophic lateral sclerosis.

Prilenia Announces Plans to Initiate Global Phase III Study of Novel ALS Treatment

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Utility Therapeutics, a UK-based biotechnology company, announced that the FDA has granted priority review to its new drug application (NDA) for pivmecillinam, a European-approved treatment of uncomplicated urinary tract infections (UTIs).

, UTIs occur far more frequently in women, with 20% having at least one in their lifetime. It is responsible for at least 8 million visits to healthcare facilities in the US per year. Bladder infection is the most common type of UTI.

Pivmecillinam, marketed under the brand name Pivya, has been used outside of the United States to treat uncomplicated UTIs for over 40 years. According to a Utility Therapeutics press release, the antibiotic has a clinical cure rate of 95% and it is recommended as a first-line option for UTI treatment in many countries, including Denmark.

"This is a product that's been well-studied, it's been widely used across Europe, and it's on numerous guidelines as a first-line option," said Utility President and CEO Tom Hadley in a press release.

Utility Therapeutics acquired US rights to the drug in 2018 along with mecillinam, an intravenous formulation for which the company has submitted an NDA. Both drugs received the FDA's qualified infectious drug product designation in 2018. According to the release, if pivmecillinam is approved by the FDA, it would be the first new antibiotic approved in the United States for uncomplicated UTIs in over 20 years.

Hadley added in the press release that three of the most commonly prescribed first-line options for uncomplicated UTIs—nitrofurantoin, Bactrim (sulfamethoxazole and trimethoprim), and fluoroquinolones—are increasingly limited by resistance, efficacy, and safety issues, illustrating a clear unmet need.

"There are 30 million prescriptions written for antibiotics for uncomplicated UTIs every year, and over 90% of those are for those three products," Hadley said in the press release. "There's a huge need, and doctors need options."

The NDA includes six clinical studies supporting pivmecillinam's efficacy and 12 supporting its safety. The FDA is expected to make a decision by April 24, 2024.

In addition to news of the FDA’s priority review, Utility Therapeutics also announced that it has received a new round of funding led by the AMR Action Fund, making it the seventh company to receive funding. The AMR Action fund was established in 2020 and aims to invest more than $1 billion with the goal of bringing two to four new antibiotics to market by 2030.

"The number of safe, effective antibiotics that clinicians have at their disposal continues to dwindle in the face of rising rates of antimicrobial resistance," AMR Action Fund CEO Henry Skinner, PhD, said in another press release from Utility. "Bringing pivmecillinam to the US will give clinicians an important tool to help patients suffering from urinary tract infections and support efforts to enhance global access to this drug."

FDA to review European-approved oral antibiotic for urinary tract infections. (17 January 2024). CIDRAP - Center for Infectious Disease Research & Policy Research and Innovation Office, University of Minnesota, Minneapolis, MN. 

https://www.cidrap.umn.edu/antimicrobial-stewardship/fda-review-european-approved-oral-antibiotic-urinary-tract-infections

Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females (26 January 2023). Medscape. 

https://emedicine.medscape.com/article/233101-overview?form=fpf

UTILITY therapeutics Ltd. Announces Financing Led by the AMR Action Fund and FDA Acceptance of PIVYA New Drug Application with Priority Review. (17 January 2024). ACCESSWIRE. 

https://www.accesswire.com/825382/utility-therapeutics-ltd-announces-financing-led-by-the-amr-action-fund-and-fda-acceptance-of-pivya-new-drug-application-with-priority-review

Pivmecillinam (Pivya) has a clinical cure rate of 95% in uncomplicated urinary tract infections and is recommended as a first-line option for treatment in many countries.

Antibiotic for Uncomplicated Urinary Tract Infections Granted FDA Priority Review

Over the past few years, the world of generative artificial intelligence (genAI) took large steps forward with the introduction of tools such as the popular ChatGPT, which have elicited excitement across all industries; however, concerns remain. Of these industries, the impact of genAI seems particularly noteworthy in the healthcare sector, according to the authors of an analysis published by 

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The study authors noted that the enthusiasm for the potential of genAI is justified, considering that an estimated 30% of the $4.3 trillion spent annually on healthcare in the United States shows little or value.

 Further, they said the excitement for genAI to enhance the quality and efficiency of healthcare is understandable, given that tens of thousands of people die each year from preventable mistakes,

 and healthcare inequity is rampant, leading to fragmented access to care.

The study authors explored the productivity paradox and how it relates to the potential impact of genAI in healthcare. It also ties the paradox back to healthcare’s previous technology “boom” with the implementation of electronic health records (EHRs) and how that can potentially predict genAI’s impact in the present.

“Although history would say yes, there are unique aspects of both genAI and healthcare’s current context that are likely to help address the challenges. If they do, genAI may deliver on its promise in health care within a few years, not decades,” the study authors wrote.

They add that previous research on the productivity paradox indicates that the primary reason why new technologies fail to rapidly achieve their fullest potential is that the earliest versions are frequently flawed and later versions are more likely to achieve a lasting impact.

“When considering whether genAI will deliver on its promise in health care, one way to shape the conversation is around two critical factors,” the authors of the article suggest. “First, is there something about genAI, compared with previous technologies, that will hasten iterative improvements in the technology? Second, is there something about the intersection of genAI and the current health care ecosystem that will accelerate the development of complementary skills and processes, or partly obviate the need for them?”

The article provides context on how the earliest versions of EHRs faced many obstacles, which led to underdelivery on initial expectations. Moving to the present, there are still obstacles that digital technologies in healthcare must overcome, which include regulatory issues, a highly concentrated market, and the large number of stakeholders in healthcare affected by these technologies.

While these challenges remain, the authors observe that genAI has the potential to bring about significant improvements in healthcare productivity and quality. They note that healthcare leaders are better prepared for the changes genAI may bring, and genAI may find early success in addressing administrative tasks. They predict the timeframe for genAI to overcome the productivity paradox in healthcare will be shorter compared to previous technologies. To achieve successful implementation, they said that leaders in the space must effectively address concerns that arise, meet regulatory standards, and perform strategic planning.

“Does that mean that health care will be completely transformed by genAI in the next few years? That seems unlikely, although certain use cases, such as digital scribes and some forms of back-office automation, could make a big difference relatively quickly,” the authors wrote. “But it does mean that what might have been a decades-long path for genAI to overcome the productivity paradox in health care may now be traversed in 5 to 10 years, and for some digitally advanced organizations, even sooner. None of this will happen automatically.”

The authors noted four key areas that demonstrate the potential of genAI to bring about rapid improvements. First, is genAI’s ease of use, which requires little user expertise to operate, as illustrated by the explosion in popularity of ChatGPT. Second, the adoption of genAI can be expedited because it can be delivered via software straight to the user’s computer.

Third, technological advances have made it easier to achieve a seamless interface between the EHR and third party genAI applications. Fourth, genAI has demonstrated the potential to improve over time with limited supervision by humans.

However, to ultimately realize the great potential of genAI in healthcare, stakeholders will need to collaborate to overcome the myriad challenges that remain, the authors concluded.

“GenAI developers will need to effectively address concerns regarding hallucinations, bias, safety, and affordability,” the authors wrote. “Regulators will need to enact standards that facilitate trust in genAI without unduly stifling innovation. 

"And, most important, healthcare leaders will need to put in place actionable roadmaps that prioritize the areas where genAI can create the greatest benefits for their organizations, paying close attention to those complementary innovations that remain necessary and striving to mitigate the known problems with genAI and any unanticipated consequences that emerge. Given the health care system’s outsized role in both human health and in economics, the stakes could hardly be higher.”

1. Wachter RM, Brynjolfsson E. Will Generative Artificial Intelligence Deliver on Its Promise in Health Care? 

 Published online November 30, 2023. doi:10.1001/jama.2023.25054

2.Berwick DM﻿, Hackbarth AD﻿. Eliminating waste in US health care. 

3. Newman-Toker DE﻿, Nassery N﻿, Schaffer AC﻿, et al. Burden of serious harms from diagnostic error in the USA. 

 To Err Is Human: Building a Safer Health System

5. Blease, C., McCarthy, J., & Ridge, D. (2023). The Use of Artificial Intelligence in Health Care: Benefits and Challenges. JAMA: Journal of the American Medical Association, 329(15), 1234–1256. 

6. Brynjolfsson E﻿, Hitt LM﻿. Beyond the productivity paradox: computers are the catalyst for bigger changes. 

Critical factors need to be addressed for pharma stakeholders to realize the full potential of generative artificial intelligence.

Generative Artificial Intelligence Could Transform Healthcare if Challenges Are Addressed

CRISPR Therapeutics has announced the completion of the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee meeting for exagamglogene autotemcel (exa-cel) for the treatment of sickle cell disease (SCD) in patients aged 12 years and older with recurrent vaso-occlusive crises (VOCs). Exa-cel is the first potential therapy to emerge from a strategic partnership between CRISPR Therapeutics and Vertex Pharmaceuticals.

During the committee meeting, which was held on October 31, 2023, independent FDA advisers praised the treatment. During the hearing, Vertex Pharmaceuticals, which developed the treatment with CRISPR Therapeutics, reported that exa-cel appears to be safe and highly effective at preventing episodes of excruciating pain that plague patients with SCD. The treatment worked in 29 of 30 patients who were followed for at least 18 months and doesn't appear to cause any serious short-term safety concerns, the company reported.

"In totality, the data support the remarkable clinical benefit of exa-cel in patients with SCD," William Hobbs, MD, PhD, vice president, clinical development, Vertex told the committee.

The FDA concurred with the potential benefits of exa-cel and did not ask advisers to take the usual step of assessing exa-cel's benefits or whether the agency should approve the therapy.

Instead, because of the high stakes of approving an entirely new kind of technology to treat people for the first time, the FDA asked advisers to focus on whether sufficient research had been done to spot "off-target" effects of the treatment—unintended editing errors that missed their mark in the DNA and that could potentially cause long-term health problems.

The advisers suggested that Vertex and CRISPR could assess the potential safety risks of their SCD gene therapy after approval. If the therapy is approved, Vertex has proposed a 15-year follow up of patients to evaluate the safety outcomes of exa-cel. This 15-year follow up will help generate data from real-time monitoring of the therapy, which uses the new gene editing CRISPR technology.

Although the advisers agreed that additional research could be helpful, several members expressed enthusiasm for the treatment.

"It's really exciting to see how many patients have been treated and how positive the results have been," said Scot Wolfe of the UMass Chan Medical School. "We want to be careful to not let the perfect be the enemy of the good."

SCD is caused by a genetic defect that produces an abnormal form of the protein hemoglobin, which red blood cells need to carry oxygen through the body. These red blood cells then get jammed inside blood vessels.

The jagged cells cause unpredictable attacks of intense pain and damage vital organs. Throughout their lives, patients with SCD are repeatedly rushed to the hospital for powerful pain drugs and blood transfusions. This affects their ability to finish school, hold jobs, or care for themselves or their families. Patients are also prone to strokes and other serious complications.

If approved, exa-cel could be the first genetic therapy available to approximately 20,000 patients with severe SCD in the United States. The FDA granted priority review for exa-cel in the treatment of patients with SCD and assigned a Prescription Drug User Fee Act (PDUFA) action date of December 8, 2023. Exa-cel’s Biologics License Application (BLA) for transfusion-dependent beta-thalassemia (TDT) was assigned a PDUFA date of March 30, 2024.

CRISPR Therapeutics Announces Completion of FDA Advisory Committee Meeting for Exagamglogene Autotemcel (exa-cel) for Severe Sickle Cell Disease. 

October 31, 2023. Accessed November 1, 2023. 

https://ir.crisprtx.com/news-releases/news-release-details/crispr-therapeutics-announces-completion-fda-advisory-committee

FDA advisers see no roadblocks for gene-editing treatment for sickle cell disease. 

https://www.npr.org/sections/health-shots/2023/10/31/1208041252/a-landmark-gene-editing-treatment-for-sickle-cell-disease-moves-closer-to-realit

FDA panel says Vertex/CRISPR to assess safety risks of gene therapy in follow-up study. 

November 1, 2023. Accessed November 1, 2023. 

https://www.reuters.com/business/healthcare-pharmaceuticals/fda-panel-says-vertexcrispr-assess-safety-risks-gene-therapy-follow-up-study-2023-10-31/

Exagamglogene autotemcel (exa-cel) has shown the potential to be a landmark therapy in preventing episodes of excruciating pain among patients with sickle cell disease.