In this article, you will learn: (1) Current FDA considerations pertaining to accelerated approval, (2) FDA expectations and recent accelerated approvals, and (3) Confirmatory trials following accelerated approval.

Regulatory Insights: FDA Accelerated Approval Strategy for Oncology Drug Development

With the vibrant new drug industry in China, many promising investigational new drugs are vying for approval in the commercially attractive US market. The unsuccessful example of the FDA Oncologic Drugs Advisory Committee meeting in February 2022 for sintilimab, for the BLA in first-line non-small cell lung cancer based on 100% Chinese data (ORIENT-11), serves as a cautionary tale for Chinese drug companies to plan thoroughly and carefully in designing/conducting clinical trials and engaging with the US FDA.

In this article, we will address the specific US regulations and FDA/ICH guidance regarding the use of foreign clinical data as the sole basis of approval and showcase a few recent success stories.

Regulatory Insights: Considerations in Seeking US FDA Oncology NDA/BLA Approval with Predominantly Asian Clinical Data

The process by which the NDA/BLA is prepared, submitted, and supported throughout its 
evaluation is a key component of the timely approval and launch of a new drug or biologic 
product. Numerous important process issues and considerations must be addressed to maximize 
success, starting with early planning.

Planning begins with a clear understanding of the goals and objectives of the project. An 
important next step is to form an appropriately qualified cross-functional team from which to 
obtain expert input (as well as management’s) on the plan. The plan should incorporate the 
appropriate research and development elements and follow the latest regulatory requirements and 
guidelines. It should be reviewed and updated periodically to reflect changes in the environment, 
both internal (i.e., chemistry, pre-clinical and clinical data) and external (e.g., competitive 
landscape, regulatory requirements, standards of clinical care, etc.)...

Success Factors for NDA/BLA Preparation

Drug development is a stepwise evaluation process on both animal and human efficacy and safety
information. Nonclinical toxicology studies play pivotal roles in estimating an initial safe starting
dose and dose range for the human clinical trials and in identifying parameters for clinical
monitoring for potential adverse effects. For an IND application, ideally it is expected that
sponsors submit final, quality-assured toxicology study reports. In addition, FDA requests
Standard for Exchange of Nonclinical Data (SEND) for specific types of toxicology studies and
safety pharmacology studies to be submitted in the IND. There are specific acceptable submission
scenarios for toxicology study reports and SEND datasets that meet FDA requirements...

IND Toxicology Study Report and SEND Dataset Requirements

The evolution of drug development from small molecules and proteins to the next generation of
cell and gene therapy (CGT) provide tremendous promise for patients. CGT products involve
complex and diverse chemistry and biological mechanisms aided by rapidly evolving scientific
research. The intrinsic material composition and putative MOA(s) of CGT products differ from
conventional drugs. Therefore, the traditional, standardized approaches for a preclinical program
may not be appropriate for evaluating the safety of CGT products. This position paper is intended
to briefly introduce the current thinking of FDA on the preclinical program development of CGT
products, and to provide Aleon’s position on the path from preclinical program to IND application
for CGT products...

Cell and Gene Therapy from Preclinical Program to IND

From bench to bedside, drug development takes an average of more than ten years. Traditionally,
drug development exposes thousands of patients in clinical trials to establish safety and efficacy
before reaching the market. In recent years, advancements in drug development, such as targeted
therapies in oncology, have shown exceptional and significant efficacy at the early stage of drug
testing. Fortunately, health authorities' have adopted expedited programs to help shorten drug
development and review timelines for especially promising drugs and biologics. This provides the
opportunity for patients with severe and life-threatening diseases to access effective and safe
treatment sooner. This position paper discusses one such FDA program known as fast track...

Fast Track Designation: How Aleon Can Help Sponsors Speed Up Their Drug Development to Serve the Underserved

Breakthrough therapy designation is a US Food and Drug Administration (FDA) program to
expedite the development and review of urgently needed investigational products (including
biologics) for serious or life-threatening conditions. To receive a breakthrough therapy designation
grant, the preliminary clinical evidence must suggest substantial improvement over available
therapy on a clinically significant endpoint.

1 Drugs so designated receive the following benefits: 2
• All Fast Track designation features
• Intensive guidance on an efficient drug development program, beginning as early as Phase 1
• Organizational commitment involving senior FDA managers

The breakthrough therapy designation has significantly shortened drug development time. A
comparison of development time for recent oncology drugs reveals that the time from submission
of an investigational new drug application (IND) to submission of a new drug application (NDA)
or biologics license application (BLA) for non-breakthrough designated drugs is median 7.4 years,
compared to only 5.2 years for breakthrough designated drugs. This is an average savings of over
two years for breakthrough...

Breakthrough Therapy Designation

Chemistry, Manufacturing and Controls (CMC) is a significant and necessary part of a
pharmaceutical application. The manufacturing process, facilities and process controls, product
characteristics, analytical testing procedures, and stability testing and results for the Drug
Substance(s) and Drug Product are included in the CMC section of pharmaceutical dossier.
Sufficient CMC information is needed to ensure the drug’s safety, identity, strength, quality and
purity...

Should CMC be a Challenge for IND Preparation

Sponsors often ask this question in one form or another: “is a pre-IND meeting really necessary
for my program?” This is just one of the many important questions for the sponsor as the early
development project moves forward to the next vital stage. For a majority of the IND preparation
and submission projects which Aleon Pharma International, Inc. (“Aleon”) has managed, the
sponsor ultimately decided that having a pre-IND meeting is necessary. These pre-IND meetings
added significant value. We understand that every program is different and faces its own unique
challenges. The decision on whether or not to have a pre-IND meeting is very important to the
sponsor and it should not be taken lightly...

Is a Pre-IND Meeting Necessary for Your Program?

You are an innovative company and your team has spent years developing a promising new drug,
exhausted a number of resources, taken several risks, and pitched your drug to potential investors.
You have gotten this far, now what? It is time to prepare for the next big step – the Investigational
New Drug (IND) application. The IND application is arguably one of the most critical stages of
drug development. A strong application is the first step in successfully developing and ultimately
bringing your drug to market. Compiling an application may seem overwhelming given the very
detailed presentation format demanded by FDA for each of the many IND components. These
include chemistry, manufacturing and controls (CMC) information, preclinical (PD, PK, and Tox)
study reports and integrated summaries with detailed listings, plus information on available and
planned human PD, PK and clinical information., and so on. With Aleon’s expertise, we can
alleviate the stress, overcome the challenges, and address any issues that come with filing. We
streamline the process by helping you prepare the IND application with a customized strategy to
suit your unique needs. We are a one-stop full service company consisting of strategic planning,
project management, preclinical, CMC, regulatory writing, and eCTD submission teams, we will
ensure that you have everything you need for a successful IND application assisting you each step
of the way...

How Aleon Effectively Manages the IND Preparation Process

Orphan diseases or conditions, as the name implies, have been historically underserved because
they afflict only a tiny portion of the population. The National Organization for Rare Disease
(NORD) estimates that that up to 30 million Americans suffer from as many as 7,000 rare diseases.
Many rare diseases lack satisfactory treatments.
The term orphan drug was coined in 1983 to describe medicines intended for the prevention,
diagnosis, and treatment of diseases so rare that pharmaceutical companies were unable to recover
the research and development investment associated with them.
The U.S. Food and Drug Administration (FDA) initiated change with passage of the Orphan Drug
Act in 1983. Many countries followed suit, with the European Parliament passing the European
Union (EU) Regulation on Orphan Medicinal Products in 1991. Although the relevant laws vary
by country, global health authorities recognized the need to create unique pathways to encourage
pharmaceutical companies to develop life-saving medications for patients suffering from rare
diseases. Tax credits for trial costs, grants, and patent exclusivity were incentives established to
relieve substantive development burdens and galvanize the incentives for the emergence of new
treatments...

Orphan Drug Designation: How Aleon can Help You bring the Miracle to Patient Care

Biosimilar products are generally recognized as the biologic version of the small molecular
generic drugs. However, there are significant differences between the small molecular generic
drugs and biosimilar products due to the inherent nature of the small molecules and biologics. The
small molecular drugs are usually low molecular weight, stable, with well-defined structure and
are completely characterized chemicals produced by process-independent chemical synthesis. On
the other hand, biologics are mostly high molecular weight, relatively unstable, complex and
heterogeneous structures, impossible to fully characterize, and typically produced from living cell
cultures by process-dependent manufacturing....

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