Aleon is pleased to announce that we will be hosting a webinar on Thursday, July 18, 2024 with the topic of "The Importance of Regulatory Due Diligence in Product Transactions."

The Importance of Regulatory Due Diligence in Product Transactions

Aleon Pharma International, Inc. is pleased to announce that we will be attending BIO 2024 in San Diego, California on June 3-6, 2024

BIO 2024 in San Diego, California on June 3-6, 2024

Aleon held an offline event on Friday, April 12th (CST) in Shanghai. The theme of the event was New Drug Development: From Late-Stage Clinical Study to NDA/BLA. Aleon shared the most valuable regulatory affairs experience and regulatory strategy at the event.

Aleon Shanghai Event

Aleon Pharma International, Inc. is pleased to announce that we will be attending the 2024 SAPA Investment Forum at JPM: Global Collaboration in Healthcare and Innovation on Sunday, January 7 in San Francisco.

2024 SAPA Investment Forum at JPM: Global Collaboration in Healthcare and Innovation in San Francisco

Q1 2023 Aleon Regulatory Frontiers Newsletter

Aleon Regulatory Frontiers Q1 2023

As a regulatory affairs consulting company, we fully understand that staying informed about regulatory affairs in the pharmaceutical industry can be quite challenging. Our goal with this quarterly newsletter is to keep you up-to-date as you navigate the complex world of regulatory affairs.
 
In this edition, you will find the following articles prepared directly by Aleon staff members:

- Is a Pre-IND Meeting Necessary for your Program?
- Increased Focus for Orphan Drug Development 
- eCTD Submissions in China, What You Need to Know
- IND Submissions in Multiple Markets
- FDA Drug Development Outlook in 2023 & Beyond

We hope that you find this information useful, and we truly look forward to staying connected and serving you throughout your journey.

Rare diseases are defined in the US as diseases or conditions that affect fewer than 200,000 individuals. The relatively small patient population has historically meant therapies are harder to come by. Pharmaceutical companies were focused on more prevalent diseases given the larger number of patients in need, and trials for rare diseases were more costly to run, even finding patients was significantly more difficult.  

     The FDA has taken great efforts to correct this problem as roughly 7,000 rare diseases affect more than 30 million people throughout the US. One major step the FDA took was the introduction of the Orphan Drug Designation program following the Orphan Drug act of 1983, a step quickly replicated by countries around the world. The policies are different in each country, but generally they provide incentives (tax breaks, exclusive marketing rights, etc. The US Marketing Application fee can be waived which currently costs more than $3 million USD) for companies to develop therapies targeting rare diseases, and since then the number of new therapies for rare diseases has increased dramatically. From 1967 to 1983 the FDA approved 34 drugs that would have qualified for the Orphan Drug Program. From 1983 to 2020 the FDA has granted more than 4,700 Orphan Drug Designations and approved more than 700 new treatments. Last year alone 26 of CDER’s 50 new drug approvals were for rare diseases. https://www.fda.gov/news-events/fda-voices/cder-continues-make-rare-diseases-priority-drug-approvals-and-programming-speed-therapeutic. However, many rare diseases are still lacking treatment. The roughly 700 approved therapies mean that 90% of the rare diseases in the US still do not have approved treatments. It is therefore no surprise that CDER is increasing focus on rare disease treatments with the introduction of the Rare Disease Cures Accelerator-Data and Analytics Platform in 2018, the Standard Core Clinical Outcome Assessment Grant Program in 2019, CDER’s Accelerating Rare Disease Cures Program and the Action Plan for Neurodegenerative Disease including Amyotrophic Lateral Sclerosis (ALS) in 2022, and the upcoming Rare Disease Endpoint Advancement Pilot program in 2023.

     CDER and the FDA are committed to seeing more therapies for rare diseases in the coming years, and we at Aleon Pharma International are dedicated to supporting sponsors seeking Orphan Drug Designations. Aleon provides regulatory strategy during the process with up-to-date regulatory affairs knowledge and experience demonstrated by years of professional relationships with health authorities. Following best practices based on experience and past FDA feedback, Aleon develops a thorough internal review checklist to capture key items during the request preparation and review periods to ensure high-quality submissions. As a result, our sponsors gain approval even in challenging situations like Orphan subset or early stage development with only in vitro data available. Supporting sponsors through an Orphan Drug Designation application is essential to getting these treatments into the hands of patients as soon as possible. Aleon is proud to have helped with more than twenty successful ODD designations in the US, and in 2022 we are hard at work with sponsors on more designations in the coming months. If you are considering an Orphan Drug Designation request to FDA, please consult us today.

Rare Diseases Remain Underserved, FDA & Aleon Increase Focus on Orphan Drug Designations

Aleon Pharma International, Inc. is supporting several Investigational New Drug Applications (INDs) for combination products, including an upcoming submission this year. A combination product is defined in 21 CFR 3.2(e), but is generally described as a product that involves some combination of a drug, biologic or device. These submissions can be more difficult than a traditional IND, and present regulatory challenges that are tricky to predict when a sponsor begins preparing an IND.

     Combination products involve different medical product centers within the FDA. While traditional products have a corresponding center within the FDA (such as The Center for Biologics Evaluation and Research – CBER, the Center for Drug Evaluation and Research – CDER, or the Center for Devices and Radiological Health – CDRH), combination products often involve multiple centers as well as the Office of Combination Products. This can make approval challenging as the submissions involve components that could be evaluated under different authorities raising questions about policy and review. The FDA has put together a Combination Products Policy Council (https://www.fda.gov/combination-products/about-combination-products/combination-products-policy-council) to resolve questions and guide policy, but when a sponsor’s approval is on the line, support from a firm like Aleon can help to avoid issues before they arise and avoid any potential delay.

     The FDA predicts an increasing number of combination product INDs as product types further overlap and combination research continues, so experience and connections within the FDA will continue to be indispensable assets when planning for a combination product submission. Aleon has successfully supported several of these INDs without issue and is currently preparing multiple INDs for combination therapies. We are well positioned to support sponsors looking at combination product approvals by the FDA.

Sponsors Continue to Look to Aleon for Combination Product INDs

On November 30th, 2022, our eCTD team faced a worthy challenge as they worked to submit three Investigational New Drug (IND) applications to the U.S. Food and Drug Administration (FDA) in a single day. This was no small feat, as the IND submission process is complex and time-consuming.

     Our team, composed of experienced regulatory affairs professionals and former FDA employees, worked tirelessly to prepare the necessary documentation and ensure that each application was complete and accurate. Preparing three INDs for submission in one day is challenging for several reasons. First and foremost, the sheer volume of information that must be included in an IND application can be overwhelming. Each application requires extensive data on the safety and effectiveness of the investigational drug, as well as detailed information on the manufacturing process and the proposed clinical trial.

     Additionally, the FDA has strict requirements for the format and organization of the information contained in an IND application. Any deviation from these requirements can result in delays or even the rejection of the application. This means that our team had to carefully review each application to ensure that it met all of the FDA’s requirements.

     Finally, the process is not complete once the eCTD team successfully submitted the applications. Each IND submission then triggers the 30 day review period FDA, during which our team keeps close communication with the FDA and must be ready to quickly and accurately respond to questions from authorities on all three projects.

     Despite these challenges, our eCTD team was able to successfully submit all three IND applications on the same day. This accomplishment is a testament to the team’s hard work and dedication to ensuring the success of our investigational drugs.

      Looking ahead, our team will continue to work closely with the FDA to move these INDs through the review process and bring these potentially life-saving drugs to patients in need.

Aleon’s eCTD Team Submits 3 INDs in One Day

China has been on a steady push to grow its pharmaceutical industry since the start of the 21st century. In 2009, it had the 9th largest pharmaceutical industry in the world and within a decade it had become the second largest, only surpassed by the US. To keep pace with the growing needs, the NMPA recognized the need for a full electronic format to expedite the review and approval of new therapies and announced an eCTD submission system for New Drug Applications (NDAs) and Biologics License Applications (BLAs) in
2021.  

     There are a few interesting things to note about China’s now-active eCTD system. Foremost among them, the system’s specifications are based on ICH 3.2.2., a technical standard, but one that very closely aligns with the FDA’s specifications rather than the EMA’s eCTD process. This will make US and China submissions even more streamlined, especially for companies already deeply familiar with the FDA’s eCTD process. There are still some differences however, language and numbering requirements are different, plus China is still developing this system – for the moment paper submissions are still needed, and eCTD submissions themselves are completed via CD as the NMPA works on a portal for gateway submissions. Aleon, with our experienced eCTD team, prepared to support sponsors for their eventual eCTD submissions as soon as the announcement came from the NMPA, and this month engaged in our first eCTD submission project for an NDA in China.

Aleon Starts eCTD Submissions for NDA in China

Investigational New Drug Applications to the US & China

Aleon has completed yet another milestone – two successful IND submissions for one product, one submission to the FDA and one to the NMPA. Sponsors may consider many different markets when developing their product. Although it is challenging to submit an IND application to more than one country (the regulatory requirements can vary significantly), Aleon has a streamlined process and great synergy working closely with our Suzhou team in China which makes this process easier for the sponsor. In fact, a submission to the FDA followed by the NMPA (as was just recently completed at Aleon) can significantly strengthen the latter, as feedback from the FDA can help guide the submission process at the NMPA and help sponsors confirm their approach. Given both the size and increasing harmony of requirements, we predict many more sponsors will adopt the approach of submitting an IND in both the US and China in the coming years.

Successful IND Submissions to both FDA & NMPA

Aleon is proud to announce the initiation of the Aleon Bravo Award Program! This program, conducted internally for our staff, is a way to recognize and celebrate the outstanding work performed by all members of our team at Aleon. Awards are given out in recognition of employees who exceed expectations for creativity and innovation, leadership and respect, dedication, quality, or collaboration with our clients. Aleon’s most vital asset is our talented staff members, and to them we say, “Bravo!”

Aleon Bravo Award Program

Aleon is attending two trade shows this summer conducted by the Drug Information Association (DIA). The first show, DIA Global 2022, will take place in Chicago later this June. The second show, DIA China 2022, takes place in Suzhou, China in late July. Founded in 1964 in response to the harm done by Thalidomide reaching the market without adequate review, DIA has committed itself to drug development education and fostering cooperative efforts around the globe. Aleon, a boutique consultancy founded in the same vein as the DIA, is dedicated to supporting sponsors as they seek approval in major markets and can assure a drug development program will not encounter unforeseen impediments. We will be attending these shows to connect with sponsors seeking support or simply seeking to learn more – stop by our booths to join the conversation!

Aleon Prepares for Two DIA Tradeshows

Aleon is excited to announce that our team has received another Fast Track Designation acting on behalf of our client! As mentioned in our previous post, Fast Track is a process at FDA designed to expedite the review and approval of drugs that treat an unmet medical need for a serious medical condition. Once a Fast Track Designation is granted, the sponsor is eligible for Rolling Review, more frequent and detailed FDA meetings, and Accelerated Approval and Priority Review if certain criteria are met. Aleon is dedicated to supporting our clients so that their innovative products can reach patients sooner.

Another Fast Track Designation Received

Aleon employees return to the office next month after months of remote work. Following a successful return to office this Fall, Aleon elected to have its employees work from home in the face of the new Omicron variant. Now, with cases significantly lowered, Aleon is once again returning to the office. Still implementing our Healthy Business plan certified by Peak Performance this Fall, Aleon employees confirmed they were ready to return to this office in May and look forward to greeting each other in person!

Aleon Returns to Office

New Drug Application Collaboration with sponsor

Aleon recently began collaborating with one of our sponsors on two New Drug Applications (NDAs) to the FDA for their small molecule drug products. Sponsors may attempt submissions on their own, but considering the significant investments that come prior to an NDA submission, (plus the fee charged by the FDA for NDA submissions with clinical data is roughly $3 million USD in 2022), all sponsors should seek expert regulatory support for NDAs as the cost of consultation represents only a fraction of the budget in any program and the risk of failure is significant.

     Despite the time and money invested in a sponsor’s program, NDAs are routinely rejected by the FDA. In fact, the FDA only approves around 60 new drugs every year, while rejecting about 30% of applicants. Each NDA is unique and requires intimate and varied knowledge of the FDA’s regulations and operations to be successful and sponsors would be wise to seek guidance from outside consultants especially when presenting novel drugs to the FDA.

New NDA Collaboration

Fast Track Designation received for sponsor

Acting on behalf of a sponsor, Aleon received a Fast Track Designation for the sponsor’s small molecule oncology drug. Fast Track is a process at FDA designed to expedite review and approval of drugs that treat an unmet medical need for a serious medical condition. Fast Track Designations are not easy to achieve. In a typical year the FDA grants approximately 200 designations, so consultation with a veteran regulatory team can be the difference between success and failure. Once the designation is received, sponsors are eligible for Rolling Review, more frequent and detailed FDA meetings, and Accelerated Approval and Priority Review if certain criteria are met. Dedicated to supporting our sponsors, Aleon has recently submitted another Fast Track Designation slated for approval later this spring.

Fast Track Designation Received

Early this January Aleon received a Study May Proceed letter for another successful sponsor submission. The letter was received for a novel drug targeting solid tumors, even though the project encountered some unforeseen difficulties. Bringing novel drugs through the IND stage can pose significant challenges to the most experienced sponsors when much of a project is not under their direct control. This was the case in the aforementioned submission, where the sponsor had elected to develop their novel solid tumor drug with a CDMO, or Contract Development and Manufacturing Company, only to have the CDMO impose delays on their timeline. Where many regulatory affairs providers may not be available after a delay, or impose overly costly burdens on the sponsor, Aleon’s dedicated team worked hand-in-hand with the sponsor to manage the delay, and make progress where possible in the interim. Upon receiving the Study May Proceed letter this week, the teams shared congratulations and began discussing collaboration on future endeavors.

Aleon Supports Sponsor Through Delays

Today, Aleon received a Study May Proceed letter from the FDA for an antibody drug conjugate (ADC) Investigational New Drug (IND) application that our team has prepared and submitted for our client. ADCs are a new type of drug designed primarily for targeted treatment of cancer cells. Cancer treatments are generally more effective if they are more cytotoxic, but they can also harm the patients taking them. To protect patients an ADC is designed with a very potent small molecular drug and a highly specific antibody that targets only the desired cells. Because of the complexity ADCs can make an IND considerably more challenging without support from an experienced team.

     The Chemistry Manufacturing and Controls (CMC) section of a IND filing is most affected, requiring three separate Drug Substances sections all be completed as if they were stand alone novel drugs entities – one for the antibody, one for the payload-linked intermediate, and one for the actual ADC payload. However, the ADC requires even more considerations on top of that. Filings often include the drug to antibody ratio, drug binding site, drug load distribution, conjugation’s effect on the antibody binding potency, and the amount of free drug/antibody in both formulation and human plasma. CMC requirements like this can bring a lot of ambiguity to the IND filing if sponsors have not been through the process before, and that ambiguity can result in delays or outright rejection.

     When planning a regulatory submission, it is not enough just to be aware of these different aspects, a quality CMC section should be drafted with the FDA’s approval process in mind. This can be tricky as there is no FDA published guidance on ADCs and applications are reviewed under the Center for Drug Evaluation and Research (CDER) by two different offices; the Office of Biotechnology Products (OBP) and the Office of New Drug Quality Assessment (ONDQA). Both have requirements for the IND filing, and sponsors should expect comments from both offices during the 30-day review period. Sponsors working on a novel ADC would receive a lot of value from consulting teams like Aleon who have been through the process and can lend their expertise to assure a successful submission on the first attempt.

Aleon’s Recent ADC IND Project is a Success

The official launch of China’s eCTD format will be December 29th, 2021. The Chinese National Medical Products Administration’s (NMPA) Center for Drug Evaluation (CDE) finalized the schedule back in late September in a post that can be found here: (https://www.cde.org.cn/ectd/news/viewInfoCommon/4e7e33b3bad573245871870861a8537f).

     The new format will only include marketing authorizations for the moment, and will not yet be implemented for clinical trial applications. The standard will apply to Class 1 and 5.1 drug registrations, as well as Class 1 therapeutic and preventative biologic products. Their eCTD submissions will be via CD-ROMs and a set of hard copies will still be required once the CD-ROM is received and accepted. This may seem like a minor change, but for teams with eCTD experience it is a welcome one.

     Aleon Pharma’s US and Suzhou teams started preparing for the new eCTD format in China two years ago when the change was initially announced and are prepared to seamlessly support our sponsors when the eCTD submissions begin next month. Our eCTD team’s preparation builds on thousands of successful eCTD submissions in the US, with more than 300 coming in the last year alone. Use of the eCTD format in China will likely accelerate review for most programs and eventually broaden market access. Companies considering expanding to the Chinese market would be wise to seek consultation today and get an updated view of the regulatory framework for new drug and biologic approvals in China.

eCTD Submissions Launch in China Next Month

Peak Performance Healthy Work Place Certification

Aleon Pharma International, Inc. attended the New Jersey Business & Industry Association’s (NJBIA) Healthy Business training for Workplace Infectious Disease Prevention this September and developed a comprehensive return to office plan for our employees.

     Aleon was certified by Peak Performance as a Healthy Business on October 11th, 2021, following NJBIA’s thorough review of the company’s return to office policy. Aleon’s policy lays out protocols and best practices for employees to maintain healthy social distancing while working together in an office setting. Internal training covered what to expect when returning to the office as well as how to avoid bringing an infection into the office and what to do if an employee suspects they or someone they know may be sick.

     After the NJBIA’s confirmation that Aleon’s policy was ready to be put into practice and a successful training session, all employees confirmed they were ready to return to the office. On October 20th, Aleon employees returned to the office safely after working from home for an astounding 584 days.

Aleon Returns to Office with a Healthy Business Certification

4 INDs succesfully submitted by Aleon to FDA

Aleon Pharma International, Inc. submitted four Investigational New Drug Applications (INDs) within the last week of September 2021. An IND is one of the most critical milestones for sponsors seeking the FDA’s permission to move into the initial clinical study phase in the United States. The IND consists of several sections including administrative information, a submission outline, manufacturing details & chemical information, preclinical data, and a proposed clinical trial. Once submitted the FDA must review the application within 30 calendar days and either place a clinical hold, provide guidance, or allow the IND to become active and clinical study to proceed.

     Submitting four INDs within a week is not possible without precise coordination by a seasoned team. The team at Aleon has had the experience to successfully prepare more than 100 IND submissions, with 20 of them completed in the last year alone. An IND is a complicated, technical application with many potential challenges, so experience is the best guide when preparing for an IND submission to the FDA. Sponsors can underestimate the time and resources required for a successful submission until they’ve been presented with many of the issues that can arise during the process. Aleon was able to submit all four applications without any delays because our experience has guided how we plan for the unexpected and anticipate the requirements of the FDA.

     To ensure sponsors will have adequate time to prepare their IND, Aleon typically engages sponsors about six months prior to their targeted submission date. Although each sponsor’s program is unique and requires specific expertise, our team coordinates submissions for different indications all the time. Aleon’s four submissions in the last week of September 2021 include programs for small molecules (for non-Hodgkin’s lymphoma as well as solid tumors), and biologics (for metastatic non-Hodgkin’s lymphomas and advanced solid tumors).

Aleon Submits Four INDs in the Last Week of September

Aleon Pharma International, Inc. recently drafted and submitted another full waiver for an initial Pediatric Study Plan (iPSP) on behalf of one of our sponsors for a program to treat relapsed or refractory peripheral T-cell lymphoma. If approved, this waiver exempts the sponsor from some of the iPSP requirements of an IND submission. The iPSP is an outline of a study or studies that will be conducted to confirm that a particular drug or biologic is suitable for use in pediatric populations and needs to be submitted as part of an IND submission. The plan covers essential parts of study design such as the age groups involved, statistical approaches to be used, and the relevant endpoints of each particular study. These study designs are important and need to be carefully crafted because pediatric populations are diverse and there can be issues with recruitment, design, cost, and ethical constraints.

     Under current regulation, FDA mandates sponsors submit an iPSP during the IND phase of development. However, if sponsors meet certain criteria, such as having evidence suggesting that a drug or biologic under consideration poses a risk to pediatric age groups, does not represent a meaningful benefit, or if the study itself would not be plausible, then sponsors are no longer required to submit an iPSP and can instead submit a full waiver. The benefit of a full waiver is the reduced requirements for submission as a full waiver only requires a few sections of the iPSP document be completed. These sections contain information on the condition/disease, the drug/biologic, the reason for a waiver, and any agreements made with other regulatory authorities that concern pediatric studies. In lieu of the waiver process, a sponsor may instead request a deferral and propose delaying the study until a later date (typically until some data is received or marketing approval is obtained). At Aleon, we review each sponsor’s program carefully and use our experience and expertise to determine if and how an iPSP waiver would be part of your drug development strategy.