Why Did My NDA Become a BLA on March 23, 2020?

During these challenging times when the world is focused on COVID-19 and the matters at hand, it’s understandable if you didn’t take much notice of March 23 as a significant date – one that’s been on the FDA’s radar for a while. March 23, 2020, was the date when certain New Drug Applications (NDAs) were deemed Biologic License Applications (BLAs). Below are key milestones in the timeline that illustrate how we got here:

  • March 23, 2010 – FDA enacts Biologics Price Competition and Innovation Act of 2009 (BPCI Act)
    Pursuant to this Act, any applications for biological products approved as NDAs would be “deemed to be” BLAs as of March 23, 2020.  This mainly applied to those protein products that were not chemically synthesized polypeptides.
  • December 2018 – FDA publishes guidance for industry
    The FDA guidance Interpretation of the “Deemed to be a License” Provision of the Biologics Price Competition and Innovation Act of 2009 provided sponsors with precise details regarding the statutes and specifics for certain types of applications. 
  • September 24, 2019 – FDA posts Preliminary List of Approved NDAs as of August 31, 2019, that will be converted to BLAs
  • Now – FDA publishes comprehensive list of Approved NDAs that were considered to be BLAs on March 23, 2020

This list includes those NDAs approved as of December 31, 2019.

If a sponsor had a pending application for a protein product under section 505 of the FD&C Act prior to this date, they would have needed to be in discussions with the FDA about their plan to transition to be in conformity with the requirements under section 351 of the Public Health Service Act. If you are a sponsor who has an NDA that is being converted, the FDA should have sent a letter on March 23, 2020, advising you that your approved application no longer exists as an NDA, but rather is now considered a BLA and will be regulated accordingly. 

The technicality around this action was triggered by the Biologics Price Competition and Innovation Act of 2009, which clarified the statutory authority under which certain protein products would be regulated by amending the definition of a “biological product” to include a “protein (except any chemically synthesized polypeptide).”

Why does all this matter? Most importantly, this deadline means that any follow-on products for these NDAs will need to win approval as a biosimilar. Sponsors will need to deploy the proper regulatory strategies and guidance that support the development of a biosimilar. If you are a sponsor that has an NDA that has been converted to a BLA or you are seeking to develop a regulatory strategy for future development of a “biosimilar,” please reach out to our Regulatory experts.

Gene Therapy in Dermatology: Transfer Techniques and Delivery Systems

Gene therapy holds the potential of long-term efficacy or even a cure for diseases with an underlying genetic basis, offering hope to patients with currently incurable diseases.

The use of gene therapy for dermatologic conditions is attractive for many reasons:1

  1. As the largest organ of the human body, skin is easily accessible for gene delivery
  2. The skin is a superficial organ, making it easy to manipulate and evaluate
  3. The skin is associated with a variety of monogenic diseases, conditions that arise from a well-defined single gene mutation

Despite factors that make the skin a desirable target for gene therapy, there are still no FDA-approved gene therapies for any dermatologic indications. Early efforts aimed at developing an effective gene therapy for skin diseases were hampered by several key hurdles:2 3

  1. Challenges in inducing sustained gene expression in vivo
  2. Difficulties in targeting genes to stem cells
  3. Obstacles in traversing the layered structure of the skin to achieve targeted, uniform transfer to different skin compartments

In this article, we review gene transfer techniques and gene delivery systems that could potentially be used for treating dermatologic conditions.

Gene transfer techniques

There are two primary approaches for gene transfer:

  1. In vivo gene therapy, where genetic material is transferred using a vector directly into the patient’s skin
  2. Ex vivo gene therapy, where cells collected from the patient using a skin biopsy are cultured, genetically manipulated, and then re-administered to the patient via injection, grafting, or some other method

The preferred approach will depend on the underlying dermatologic condition, as well as the vector used for gene delivery.

Viral vectors for gene delivery

The epidermis was one of the first targets for in vivo experimental gene transfer, where vectors are administered directly to the patient.4 While there are non-viral gene delivery systems, viruses — particularly retroviruses — remain the most commonly used vectors for cutaneous gene transfer. Retroviral vectors transcribe their RNA into DNA and then integrate into the infected host genome. For epidermal stem cell populations, which have a low mitotic rate, lentiviral vectors may be preferred for in vivo therapy due to their ability to infect non-dividing cells.1 For ex vivo gene therapy, both oncoviral and lentiviral vectors have demonstrated the capacity for long-term therapeutic gene expression in skin.5 6 Adenoviruses, the most commonly used gene therapy vector across all therapeutic areas, have demonstrated only about two weeks’ expression in the skin, which may limit their utility in dermatologic conditions that require long-term expression.1

Non-viral vectors for gene delivery

Compared to viral vectors, non-viral vectors such as plasmid DNA may be more cost-effective, less toxic, and less immunogenic. Non-viral gene transfer is typically characterized by short-term gene expression and low transfection efficiency, which may be desirable for wound healing. While the preferred method of cutaneous DNA delivery is topical application, the efficiency of transgene delivery with this route is low as the stratum corneum limits DNA transport.1

Other methods for physical or mechanical delivery of genes include ultrasound- or electrical field-mediated gene transfer, magneto-permeabilization, and microneedles. Research has also focused on methods such as biodegradable nanoparticle carrier systems for enhancing the efficiency of topical, dermal, or transdermal gene delivery. However, due to low transfection efficiency in vivo compared with viral vectors, nucleic acid vectors may have limited utility for gene therapy in skin diseases.

What to expect in the future

To date, the most significant clinical advances in gene therapy for dermatologic conditions have been made in epidermolysis bullosa, with three companies currently conducting pivotal trials.7 Gene therapy is also being actively studied for melanoma and ichthyosis.8 9 We will explore these advances in the next article in our dermatology gene therapy series.

There remains room for additional progress. Of the 1,052 clinical trials involving gene therapy, gene-modified cell therapy, cell therapy, and tissue engineering, only 22 studies are focused on dermatologic conditions.10 Advances in the molecular characterization of dermatologic diseases continue to deepen our understanding of the underlying pathogenic processes and gene expression profiles involved in skin disorders. With continued optimization of vector design and gene transfer strategies, as well as the development of imaging tools for monitoring gene delivery and treatment response, we expect to see an increase in the number of dermatology gene therapy trials in the coming years.

With expertise across most major dermatological indications, more than 190 rare disease studies in the past five years, and product development experience with multiple next-generation biotherapies including gene therapy, Premier Research is uniquely positioned to support innovators in this developing field. Contact us today to learn more.


1 Gorell E, at al. Gene therapy for skin diseases. Cold Spring Harb Perspect Med. 2014;4(4):a015149.

2 Somani AK, Esmail N, Siminovitch KA. Gene therapy and dermatology: more than just skin deep. J Cutan Med Surg. 1999;3(5):249-259.

3 Kaspar RL, et al. Imaging functional nucleic acid delivery to skin. Methods Mol Biol. 2016;1372:1-24.

4 Williams RS, et al. Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles. Proc Natl Acad Sci. 1991;88:2726-2730.

5 Larcher F, et al. Long-term engraftment of single genetically modified human epidermal holoclones enables safety pre-assessment of cutaneous gene therapy. Mol Ther. 2007;15:1670-1676.

6 Siprashvaili Z, et al. Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue. Human Gene Ther. 2010;1299-1310.

7 Evaluate. Gene therapies go skin deep to tackle epidermolysis bullosa, March 11, 2019. Available at https://www.evaluate.com/vantage/articles/analysis/spotlight/gene-therapies-go-skin-deep-tackle-epidermolysis-bullosa. Accessed March 18, 2020.

8 ClinicalTrials.gov. Search for melanoma gene therapy, March 18, 2020.

9 ClinicalTrials.gov. Search for ichthyosis gene therapy, March 18, 2020.

10 Alliance for Regenerative Medicine. Q3 2019 Data Report. Available at https://alliancerm.org/publication/q3-2019-data-report/. Accessed February 26, 2020.

FDA Releases Draft Guidance for Transdermal Product Development

Transdermal and topical delivery systems (TDS) are important dosage forms that allow delivery of a drug to local tissue or provide systemic delivery through the skin. These drug products provide a number of advantages for patients, but can be challenging to develop. In November 2019, the FDA issued a draft guidance entitled Transdermal and Topical Delivery Systems – Product Development and Quality Considerations: Guidance for Industry.[1] The document provides the FDA’s current thinking on product design, pharmaceutical development, product quality, and the performance and safety evaluations for TDS.

Why develop a TDS product?

TDS have a number of advantages over other routes of administration. First, TDS can improve patient compliance, especially in patients with swallowing difficulties or gastrointestinal (GI) irritation. Convenience and ease of use are other key reasons for TDS development. From a drug exposure perspective, systemic absorption via TDS (through the skin) avoids potential enzymatic digestion or drug hydrolysis in the acidic stomach environment. It also avoids first pass metabolism, which can provide greater systemic levels of certain active ingredients. Additionally, due to the controlled release mechanisms of TDS, the duration of drug exposure can be designed in some cases to be prolonged for multiple days.

TDS – Development Considerations

When developing a TDS product, a number of considerations should be evaluated at the early stages of product development:

  • What is the skin permeation capability of the active ingredient? Is it safe to use on the skin?
  • Does the TDS formulation have the potential to irritate or sensitize the skin?
  • What will be the duration of the TDS application? Where will the product be applied? Will the application site need to be rotated?
  • Are the drug levels needed for efficacy well characterized? Can a sufficient dose be incorporated into the TDS?
  • Can a reasonably sized patch be developed for the indication and target population?

Two main types of TDS are the reservoir and matrix style, distinguished by how the active ingredient is incorporated into the product. A matrix-style TDS product contains the active ingredient dissolved or suspended in a matrix containing adhesive, penetration enhancers, preservatives and other excipients.

Matrix Type TDS1

A reservoir TDS product contains the drug in a heat-sealed area between the backing membrane and a semi-permeable membrane that is in contact with the skin.

Reservoir Type TDS1

The reservoir TDS design has inherent failure potential and safety risks. Strong pressure applied to a reservoir TDS can cause the product to rupture, releasing the contents of the drug-containing reservoir in an uncontrolled manner. For this reason, the FDA advises manufacturers and applicants to focus development efforts on matrix-style TDS. The guidance further states that “[a]pplicants are strongly encouraged to consult the Office of Pharmaceutical Quality early in the development process prior to pursuing a reservoir design.”

Regulatory Considerations for TDS

From a regulatory perspective, TDS products are combination products and are required to comply with 21 CFR part 4 subpart A (Current Good Manufacturing Practice [CGMP] Requirements for Combination Products).[2] This describes how 21 CFR parts 210 and 211 (drug CGMPs) and 21 CFR part 820 (device Quality System regulation) apply to combination products. Additionally, developers of TDS should be aware of the design control regulations outlined in 21 CFR part 820.30, to confirm there are no negative interactions between the product’s constituent parts and to make sure the combined use results in a combination product that is safe, is effective and performs as expected.

The Quality Target Product Profile (QTPP)

In the guidance, the FDA recommends that before initiating the development of a TDS product, applicants should establish a Quality Target Product Profile (QTPP), outlining the quality characteristics of the product and taking into account its safety and efficacy. The QTPP may include the following:

Additional QTPP elements may exist depending on the indication, or other functional requirements, such as the size of the finished product, which may depend on the location on the body that the TDS product is to be applied.

Critical Quality Attributes

Early in product development, applicants should establish a list of critical quality attributes (CQAs). Using the QTPP as a guide, applicants should outline the CQAs that define the physical, chemical, biological or microbiological properties or characteristics that should be within an appropriate limit, range or distribution to ensure the desired product quality. This list of CQAs will likely evolve over the product development lifecycle, as additional information is obtained.

The FDA guidance summarizes typical CQAs for the drug substance, drug product and excipients for TDS. Notable for TDS are the qualification of adhesives; the guidance outlines parameters for evaluation of adhesive polymers as raw materials, adhesive as a laminate (in the absence of the Active Pharmaceutical Ingredient [API] and other excipients), and adhesive in the final product (along with drug substance and other excipients and components).

Another important attribute of the TDS is the identifying information printed on the product itself. This should be established early in development to ensure that the labeling process or inks used for printing do not interact with the TDS, and to assess inks in extractable/leachable studies. Applicants should be aware that products that are clear or colored to match human skin tone can make it difficult to find the TDS on the patient; this can lead to potential medication errors (for example, if the product becomes unknowingly detached or through the application of multiple products). Therefore, it is recommended that the backing membrane is printed with ink of adequate contrast for easy identification.

Information to be Submitted in an Application

The new guidance outlines the quality information to submit in a marketing application for a TDS product. The guidance describes information to include in the pharmaceutical development portion of the application, including expectations for registration and exhibit batches. For TDS, registration/exhibit batches should be manufactured from three distinct laminates, each made using different lots of API, adhesives, backing and/or other critical elements of the product. Release and stability sampling should be representative of the full length and width of the laminates to demonstrate robust manufacturing. Since TDS products are sensitive to small differences in the manufacturing process, a table comparing the clinical, BE, registration/exhibit and proposed commercial batches should be included in the application.  For each batch, the table should specify the manufacturing process used, results of critical in-process tests, yield and reconciliation data.

The guidance also describes the product characterization studies, manufacturing information and control evaluations to be completed for TDS products when preparing a marketing application. This includes evaluations of crystallization potential of the formulation, residual drug assessment, the effects of heat on drug delivery and adhesion testing. Both in vitro and in vivo adhesion testing should be performed, with in vivo assessments representative of real-world use.

Conclusions and Recommendations

The development of TDS is important, as there are many patients that benefit from these products. The new draft guidance provides a much-needed perspective on the FDA’s expectations for the development of these products, and how applicants should develop and properly characterize these products for a marketing application. In addition to the information provided in the new guidance, meeting with the FDA early in the development program is recommended and will help clarify the nonclinical, clinical, quality and regulatory requirements specific to a given program.

Is your company considering developing a TDS product? The experts at Regulatory Professionals (RPI), A Division of Premier Research, have assisted in the development of TDS products through all stages and can provide guidance and expertise for your program. For more information, contact us.


[1] Center for Drug Evaluation and Research. (2019, November). Transdermal and Topical Delivery Systems – Product Development and Qua. Retrieved from https://www.fda.gov/regulatory-information/search-fda-guidance-documents/transdermal-and-topical-delivery-systems-product-development-and-quality-considerations

[2] Center for Drug Evaluation and Research. (2017, January). Current Good Manufacturing Practice Requirements for Combination Products. Retrieved from https://www.fda.gov/regulatory-information/search-fda-guidance-documents/current-good-manufacturing-practice-requirements-combination-products

Contract Pharma – Realizing the Full Potential of Precision Medicine in Oncology

Innovation in oncology drug development is being driven by “precision medicine.”

Precision medicine promises a new paradigm in oncology where every patient receives truly personalized treatment. This approach to disease diagnosis, treatment and prevention utilizes a holistic view of the patient—from their genes and their environment to their lifestyle—to make more accurate decisions.

Growing at a rate of 10.7 percent, the precision medicine market is expected to exceed $96 billion by 2024. Bioinformatics represent a significant share of the market, as bioinformatics tools enable the data mining necessary for rapid identification of new drug targets and repurposing of existing treatments for new indications.1 (Reuters) The oncology segment of the precision market is expected to experience an 11.1 percent compounded annual growth rate (CAGR) leading up to 2024 due to the success of recent targeted therapies and subsequent high demand.

Still, precision medicine is in its infancy, and making personalized treatment a reality for all patients requires a transformation in how novel therapies are developed and delivered. New regulatory, technical, clinical and economic frameworks are needed to ensure that the right patients are able to access the right therapy at the right time. In this article, we review the current state of precision medicine in oncology and explore some of the challenges that must be addressed for precision medicine to reach its full potential.

Read the full article at Contract Pharma.

Applied Clinical Trials – Patient Engagement and Advocacy: Advancing the Cause of Clinical Drug Research

Duchenne muscular dystrophy (DMD) patients almost universally lose the ability to walk as the disease progresses. Patients generally understand that loss of ambulation is to be expected, and as was learned from a patient preference study, they tend to put greater priority on maintaining use of their hands. Yet for many years, DMD drug trials included a specific endpoint requiring that they enroll only patients who were still able to walk—denying eligibility to a potentially large number of participants.

That changed when a DMD-focused advocacy organization took the matter up with the Food and Drug Administration (FDA) and helped develop new trial guidelines that allow some non-ambulatory patients to participate in these trials.

Engaging patients in clinical trial design is essential to ensuring that researchers devise relevant criteria, establish realistic expectations, and pursue goals that are meaningful to the study participants who are central to the success of these costly and risky endeavors. The expanding number and influence of patient advocacy groups in recent years—the National Organization for Rare Disorders lists nearly 1,900 such organizations on its website—underscore the fact that patients are not passive subjects, but people who approach clinical trials with varying degrees of hope, fear, doubt, skepticism, anxiousness, and countless other emotions.

Some may find symptom relief or even a disease modifying therapy, while others won’t have the same outcomes. Some recognize that the study drug won’t benefit them personally, but enroll so they might help others. What unites patients and families who participate in clinical trials is their willingness to sacrifice their time, energy, and so much more for an exercise whose outcome is uncertain at best.

Read more at Applied Clinical Trials.

IEEE Spectrum: Cyber attacks on Medical Devices Are on the Rise—and Manufacturers Must Respond

Cyberattacks are increasingly common in the health care industry. As the number of networked medical devices increases, so does the urgency for makers of these devices to understand and mitigate threats to device security.

In an increasingly interconnected and digital world, more and more medical devices contain embedded computer systems, which can be vulnerable to security breaches that affect how these devices operate. In March 2019, the U.S. Food and Drug Administration (FDA) issued a warning about two security flaws affecting dozens of implantable cardioverter defibrillators.

Such warnings underscore the importance of a cybersecurity-minded approach to device development.

Cyberattacks can be initiated by the introduction of malware into the equipment or by unauthorized access to configuration settings and data—not only in the devices themselves, but also in the hospital or other networks to which they are connected.

Attacks on networked medical devices, and the data they collect and transmit, can be costly. Patient safety is a critical concern, especially with devices such as defibrillators and insulin pumps that could cause patient harm or death if they malfunction.

Hacking of data from networked devices can also reveal commercially valuable information, such as:

  • Patient health data, which can be sold, used to run phishing schemes, or be combined with other mined data to facilitate identity theft
  • Product performance data, which can be sold to competitors or manipulated to undermine the device maker’s safety and efficacy claims
  • Data from other devices connected to the same network, which can have system-wide impacts

Judging the risk of an attack

There are a number of factors that contribute to cybersecurity risks in the medical device sector. These factors include:

  • Use of off-the-shelf software
  • Advances in the Internet of Things (IoT), which blur the lines between public and private data and make it easier for health information to be shared electronically
  • Proliferation of wearable and at-home medical devices, as well as telehealth offerings
  • Lack of a mandate for health care facilities to retire from use devices that are no longer supported by the manufacturer
  • Limited collaboration between the makers of medical devices and the health care delivery organizations that implement those devices

Over the past few years, the FDA has been vocal about the need for increased cybersecurity for medical devices. Since the FDA published its first premarket cybersecurity guidance in 2014, the agency has issued two other guidance documents. In 2016, the FDA published a postmarket guidance, which provides recommendations on how manufacturers should respond to new cybersecurity threats for marketed devices. In October 2018, the FDA issued an updated draft premarket guidance that also includes some postmarket recommendations.

Read more at IEEE Spectrum.

The Challenges in Fulfilling the Promise of Personalized Oncology

Personalized oncology promises a new model of cancer care where medical decisions are based on a holistic view of the patient, including their genes, environment, and lifestyle, and tailored to the molecular profile of their tumor. To date, great strides toward the paradigm of personalized oncology have been made in the area of cancer immunotherapy, which boosts a patient’s own immunity to combat tumor cells. Immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapies have dramatically improved outcomes for a select number of patients, but widespread use of these treatments remains elusive.

To make personalized cancer treatment a reality for all patients, we need to reimagine the biopharmaceutical business model and drug development process, both of which have traditionally been focused on broad drug development and blockbuster medicines. New regulatory, technical, clinical, and economic frameworks are needed to ensure that the right patient can access the right therapy in a meaningful timeframe. In this article, I discuss three key challenges that must be addressed to fulfill the promise of personalized oncology.

#1: Understanding and addressing mechanisms of resistance

The ultimate goal of cancer immunotherapy is to stimulate the immune system to launch a sustained attack against tumor cells. Given the complex and dynamic interactions between tumors and the immune system, achieving this is complicated.

The challenge lies in managing the delicate balance between autoimmunity and the immune system’s ability to recognize non-self. In some cases, the immune system may fail to recognize tumor cells as non-self and may develop a tolerance to them. Moreover, tumors have myriad methods for evading the immune system.

Resistance to cancer immunotherapy can be categorized as primary (i.e., failure to respond) or secondary (i.e., relapse after successful treatment). Approaches for optimizing response and minimizing resistance to cancer immunotherapies include developing biomarkers to assist with patient selection or treatment monitoring, altering the tumor microenvironment, and educating healthcare practitioners on the potential for delayed response with these types of treatments. With CAR-T therapies, resistance may be due to poor persistence of CAR T-cells after infusion or due to antigen loss of the target receptor.

Read more at Applied Clinical Trials.

Applied Clinical Trials – 3 Critical Challenges: Fulfilling the Promise of Precision Oncology

Precision oncology promises a new model of cancer care where medical decisions are based on a holistic view of the patient, including their genes, environment, and lifestyle, and tailored to the molecular profile of their tumor. To date, great strides toward the paradigm of precision oncology have been made in the area of cancer immunotherapy, which boosts a patient’s own immunity to combat tumor cells. Immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapies have dramatically improved outcomes for a select number of patients, but widespread use of these treatments remains elusive. 

To make personalized cancer treatment a reality for all patients, we need to reimagine the biopharmaceutical business model and drug development process, both of which have traditionally been focused on broad drug development and blockbuster drugs. New regulatory, technical, clinical, and economic frameworks are needed to ensure that the right patient can access the right therapy in a meaningful timeframe. In this article, I discuss three key challenges which must be addressed to fulfill the promise of precision oncology.

#1 Understanding and addressing mechanisms of resistance

The ultimate goal of cancer immunotherapy is to stimulate the immune system to launch a sustained attack against tumor cells. Given the complex and dynamic interactions between tumors and the immune system, achieving this is complicated. The challenge lies in managing the delicate balance between autoimmunity and the immune system’s ability to recognize non-self. In some cases, the immune system may fail to recognize tumor cells as non-self and may develop a tolerance to them. Moreover, tumors have myriad methods for evading the immune system (see Figure 1).Resistance to cancer immunotherapy can be categorized as primary (i.e., failure to respond) or secondary (i.e., relapse after successful treatment). Approaches for optimizing response and minimizing resistance to cancer immunotherapies include developing biomarkers to assist with patient selection or treatment monitoring, altering the tumor microenvironment, and educating healthcare practitioners on the potential for delayed response with these types of treatments. With CAR-T therapies, resistance may be due to poor persistence of CAR T-cells after infusion or due to antigen loss of the target receptor.

Read more at Applied Clinical Trials.

PM360 – Working with Advocates: Understanding Patient Concerns

Patient advocacy groups have exploded in number and scope in recent years and in many ways are reshaping the drug development landscape, from trial design to recruitment support to participation in the regulatory approval process. Thousands of organizations now advocate for millions of patients, and while many patients and families eagerly engage with these groups, others are more guarded in approaching them—if they entertain the idea at all.

The CRO where I am head of patient and stakeholder engagement works extensively with many advocacy groups, and while we generally see a number of advantages for patients engaging with these organizations, we never overtly recommend that patients or their families get involved with advocacy organizations. That’s because it’s a highly personal decision that patients and their families need to make, weighing their questions about privacy, being stigmatized socially as a result of the condition in question, and a number of other complex factors that vary from family to family.

A better approach for sponsors and their partners is to understand patients’ concerns about getting involved in advocacy and to support opportunities to show how engaging with an advocacy organization can benefit patients and the overall drug development process—from providing disease specific information and helping with fundraising to supporting new compounds as they move toward marketing authorization and increasing the likelihood that they qualify for insurance reimbursement.

A Diverse, Expanding Crowd

“Patient advocacy group” and “patient advocacy organization” are broad terms that describe everything from organizations that raise millions of dollars and heavily influence government policy to worried parents hunched over a kitchen table raising awareness of a condition that has suddenly upended their lives. U.S. and European regulators have encouraged proliferation of these groups: The U.S. Food and Drug Administration (FDA), through a 2012 law known as FDASIA, the FDA Safety and Innovation Act, and the European Medicines Agency via its framework for interaction among the EMA, patients, and consumers.

Read more at PM360.

Applied Clinical Trials – Managing Clinical Trial Complexity as Gene Therapy Progresses

The field of gene medicine has a history filled with hope and tragedy, successes and cautionary tales. The world’s first gene therapy was approved in Europe in 2012, only to be taken off the market five years later due to regulatory and commercial barriers. Now, more than six years after the first approval, gene therapy clinical development is thriving. And the path to patients in research settings, and ultimately to market, continues to evolve as new milestones are met and newcomers abound.

Since mid-2017, the FDA has approved three new gene therapy products, and the agency’s expressed commitment to advancing development of these treatments points to improving prospects for emerging therapeutics. This is good news for those with rare diseases and unmet medical needs, but for these new options, the trajectory from concept to trials to regulatory approval and commercial availability is a uniquely complex, but not impossible, pathway. 

New therapeutic reality

“Once just a theory, gene therapies are now a therapeutic reality for some patients,” Dr. Scott Gottlieb, the former FDA commissioner, wrote in July 2018 when announcing steps the agency was taking to support development of new drugs. “Gene therapies are being studied in many areas, including genetic disorders, autoimmune diseases, heart disease, cancer, and HIV/AIDS. We look forward to working with the academic and research communities to make safe and effective products a reality for more patients.”

Gottlieb pointed to the agency’s recent approval of three gene therapy drugs:

  • Kymriah, a treatment for B-cell acute lymphoblastic leukemia.
  • Luxturna, a drug for patients with inherited retinal disease.
  • Yescarta, a treatment for non-Hodgkin’s lymphoma.

Considering the scarcity of gene therapy drugs and the enormous effort and expense involved in conducting human trials, the emergence of three new therapies inside of a year is encouraging for sure. Still, Gottlieb cautioned, there is much we don’t understand about how these products work, how to administer them safely, and whether they will continue to work properly without causing adverse side effects in the long term.

Read more at Applied Clinical Trials.