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Clinical Studies, Phases I-IV Articles and Insights

In the News: December Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. FDA Issues Advice on Combination Products In December, the FDA published “Requesting FDA Feedback on Combination Products” to

In the News: August Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program. Fitbit developing algorithm for early detection of COVID-19 Fitbit recently posted a study that may indicate the company’s

The Missing Parts of the Inactive Ingredient Database (IID)

Yesterday, FDA released draft guidance on the use of the Inactive Ingredient Database (IID) in drug development. The guidance is one step FDA is taking to address feedback from the generics industry that IID enhancements are needed to help sponsors make the right formulation decisions. What is the IID?

Seamless Clinical Trials: Why Didn’t We Think of That?

Seamless clinical trials have become the new buzz word in drug development since FDA Commissioner Scott Gottlieb promoted their use this month. But are they new, and which products are best suited to this style of clinical trial? Oncology drugs are the obvious examples of

Alkermes Prodrug for Treatment of Multiple Sclerosis: NCE?

The Food and Drug Administration (FDA) began requiring drug efficacy, in addition to safety, for approval in 1962 based on the Kefauver-Harris Amendment. Despite this requirement, many drugs that have been approved by FDA have limited efficacy (eg, drugs that treat cancer or Alzheimer’s disease).

MannKind Breathes Easier – Inhaled Insulin Finally Approved

MannKind’s Afrezza Receives FDA Approval In June of this year, MannKind Corporation announced that they received FDA approval for Afrezza®, their rapid-acting inhaled insulin product. MannKind is currently working to identify a pharma partner to manufacture and distribute Afrezza, and the product could be available

The Road to Commercial Success – The Target Product Profile

The goal of drug product development is commercial success.  If this statement wasn’t true, how would patients access the live-saving or life-enhancing drugs we are developing.  Yet, all too many companies focus just on FDA approval, which in our view should be just a very important

505(b)(2) Prodrug Fails Phase III Study

Development of drugs for new indications entails more risk of failure than simply changing formulations.  Just ask XenoPort, which announced May 19th that its prodrug of R-baclofen, arbaclofen placarbil,   failed to show efficacy in a Phase III clinical trial. Arbaclofen placarbil was being studied for multiple sclerosis-related

KV Appeals Makena Decision

We have followed the saga of KV’s Makena for two reasons.  The most important reason is that the submission, review and approval of Makena is perhaps the best example of using a publicly funded clinical study for NDA approval, despite the clinical trial material not being sourced

Drug Development Planned Like the Titanic

How many drug development companies leave it up to the CRO or CMO to design or execute their studies or formulation/manufacturing without oversight?   Like those who boarded the Titantic 100 years ago, they seem to trust the mantra that their contractor’s work is unsinkable.  MAP Pharmaceuticals

KV’s Makena Part 4: Statistical versus Clinical Significance

In previous postings (Intro, Part 1, Part 2, Part 3), I have provided background on KV’s Makena (17a-hydroxyprogesterone caproate injection aka 17P).  The development and regulatory history contains many lessons. In this posting I’d like to examine the difference between statistical and clinical significance.  Please

KV’s Makena Part 2: Accelerated Approval Subpart H

In a previous posting, I provided background on KV’s Makena (17a-hydroprogesterone caproate injection aka 17P). The development and regulatory history contains many lessons. In this posting I’d like to examine the accelerated approval process. Makena was approved under 505(b)(2) as seen from the approval letter

Contrave® Rejection: The Long and the (Too) Short of it

On February 1st Orexigen(R) Therapeutics, Inc. and Takeda Pharmaceutical Company Limited (Takeda) announced that the FDA issued a complete response letter dated January 31, 2011 regarding the New Drug Application for Contrave® (naltrexone HCl/bupropion HCl) extended-release tablets for the treatment of obesity, including weight loss

Nuedexta® – Smart Pharmacology to Treat a Unique Disorder

The FDA has approved NuedextaÃ’(Avanir Pharmaceuticals Inc.), a drug that curbs involuntary and uncontrolled crying and laughing episodes (known as pseudobulbar affect (PBA)) that are experienced by patients with some neurological disorders. Nuedexta is the first drug to be approved to treat patients with these

505(b)(2)s with Minimal Sponsor Studies

The power of the 505(b)(2) process is realized when the sponsor has to conduct few, if any, studies to get their drug product approved. For many drugs there is wealth of data available in the public domain. The challenge is locating the data and then

Failed 505(b)(2)?: Vivus™ Qnexa

I am often asked about 505(b)(2) drug development failures. After all, 505(b)(2) is a regulatory pathway that is chosen because it is lower cost and has lower risk than a 505(b)(1). The lower risk is attributable to the reliance on the known safety and efficacy

New User Fees for 2011

FDA announced the new PDUFA user fees for fiscal year 2011 (starts October 1, 2010). The fee for a full application containing clinical data is $1,542,000.   For a supplement or an NDA not requiring clinical data, the fee is $771,000. A clinical study is generally

Pro-Drug Denied

I am frequently asked if 505(b)(2) projects fail or whether any NDA submissions are rejected. My answer is that the vast majority succeeds and are eventually approved. Those that fail more often are due to money or design issues, not execution risks. Today I discuss

GTx Needs a 2nd Phase III Trial and More Safety Data

GTx announced 11/2/2009 that it has received a Complete Response Letter from the FDA concerning its NDA for TOREMIFENE CITRATE 80 mg (ACAPODENE®). The NDA, filed in late December 2008, sought approval for use of toremifene 80 mg to reduce fractures in men with prostate cancer

A Treatment IND is NOT the same as an IND

In this blog I seldom quote or provide hyperlinks to press reports because they too often contain misleading information.  Yet, today’s DIA web summary contained an article that I just have to correct.  The article was a  summary of a report on Medpage’s website.  The

AstraZeneca ends collaboration with MAP Pharmaceuticals

MAP Pharmaceuticals announced yesterday (7/9/09) that AstraZeneca has ended its collaboration on unit dose budesonide (UDB).  This past February, MAP reported that the Phase 3 study had failed to reach its primary endpoints.  Apparently, further analysis failed to support continued development of UDB. We seldom

Quick-release bromocriptine mesylate approved

The FDA approved VeroScience’s Cycloset (bromocriptine mesylate) 0.8mg tablets on May 5 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The NDA was first submitted in 1997 – before the 505(b)(2) guidance.  The API, bromocriptine

505(b)(2) IV Acetaminophen

Cadence Pharmaceuticals announced yesterday 5/14/2009 that it had submitted an NDA for Acetavance(TM) – intravenous acetaminophen.  It is instructive to look at the clinical development plan for this 505(b)(2) product.  According to the company, the FDA required 2 pivotal Phase 3 trials: one clinical trial for

One vs. Two batches for single-dose and multiple dose studies

Today’s posting stems from a client question.  The client’s product candidate is an oral product that requires both single- and multiple dose pharmacokinetic studies. Question:  Do companies ever use one pivotal batch for single-dose (SD) study and another batch for the multi-dose (MD) study?  What

Dexlansoprazole approved for the treatment of GERD

This past Friday, 1/30/2009, the FDA approved Takeda Pharmaceuticals North America Kapidex (dexlansoprazole) for the treatment of gastroesophageal reflux disease (GERD).  Kapidex is an enantiomer of lansoprazole (Prevacid).  In addition to the change in enantiomer, Kapidex is formulated with two type of enteric-coated granules to

Watson’s 505(b)(2) Overactive Bladder Gel Approved by FDA

On 1/27/2009 Watson Pharmaceuticals announced that the FDA had approved its GELNIQUE(tm) (oxybutynin chloride) Gel 10% for the treatment of overactive bladder.  The gel product supplements a transdermal patch made by Watson (Oxytrol) which has not had the marketing success one might expect, perhaps due

505(b)(2) Combination Meets Phase 3 Goals

Horizon Therapeutics announced yesterday that its “fixed-dose combination product containing ibuprofen and famotidine, demonstrated a statistically significant reduction in the incidence of non-steroidal anti-inflammatory drug (NSAID)-induced upper gastrointestinal (gastric and/or duodenal) ulcers in patients with mild-to-moderate pain when compared to ibuprofen alone.”  Note that the

Modeling using Dissolution Data

Not only pharmacokineticists get to have fun in the modeling sandbox.  Chemists and formulators get to have their fun synthesizing data.  Let’s use an example of how dissolution data can be used for modeling.  The example is taken from a project to develop a oral

PK Modeling, not just any pretty face

We recently changed the navigation and look of our website to show that we are a full-service drug development company.  505(b)(2) drug development is so much more than just regulatory submissions!  I was asked to explain what the chart is on the pharmacokinetics (PK) services

505(b)(2) Patent & Marketing Exclusivity

IP attorney Stephen Albainy-Jenai and I just concluded a webinar hosted by DIA entitled 505(b)(2) Patent & Exclusivity.  23 different companies attended, showing the increasing interest in 505(b)(2) issues.  Earlier this year, DIA hosted my overview of the 505(b)(2) drug development process where the attendees had many questions asking

505(b)(2) with Only Phase 1 Study

We are often asked if a 505(b)(2) application always requires a clinical study (i.e., Phase 2 or 3 in patients).  The answer is a resounding NO. On January 14, 2008 ADVENTRX Pharmaceuticals announced the successful completion of a bioequivalence study that demonstrated similar blood levels and

505(b)(2) – Part 2: The Assessment: Timeline, Cash Flows

Once the clinical development plan is established, the CMC, regulatory and medical communication plans can be matched up. We use MS Project to develop a high-level overall plan.  MS Project then can be used to generate cash flows and Gantt charts.  This information can be used by

505(b)(2) – Part 2: The Assessment: Regulatory Strategy

Regulatory Strategy This section provides analysis of pertinent regulatory information to produce a recommended regulatory pathway.  A thorough search of regulatory documents supports the regulatory recommendations (e.g., Dockets Management; HeinOnline[1]). The 505(b)(2) regulatory pathway may be appropriate if part of the NDA application requirements can

505(b)(2) – Part 2: The Assessment: Clinical Development Plan

Clinical Development PlanThe proposed Clinical Development Plan is dependent on the selected regulatory pathway.  The Clinical Development Plan is based on available Agency study recommendations provided in the FDA Guidance for Industry documents, information in the public domain (e.g., PubMed), and information obtained from SBA

505(b)(2) – Part 2: The Assessment: Clinical Pharmacology

Clinical Pharmacology An overview of the proposed product’s absorption, distribution, metabolism, and excretion (ADME) is detailed in this section obtained from various resources.  An important source of information for this and other sections is the FDA reviewer summaries (Summary Basis of Approval – SBA) for

505(b)(2) – Part 2: The Assessment: Pharmacokinetic Review

A comprehensive search of the literature is performed to obtain published pharmacokinetic (PK) data for the proposed product (dependent on selected regulatory pathway). This review compares the PK profiles for all available routes and conditions of administration and dose strengths. This review includes studies assessing: Single- and

505(b)(2) Combo Plavix/Prilosec

Cogentus Pharmaceuticals is working on a combination tablet that combines clopidogrel, the active ingredient in Plavix, with omeprazole, the API in Prilosec. Cogentus’s business strategy is to: “… improv[e] the therapeutic profiles of existing, proven drugs in ways that take full advantage of their strengths while

505(b)(2) – Part 2: The Assessment: Safety Review

Of course my product is safe! – the RLD was shown to be safe. Perhaps so.  The FDA approves products based on a risk/benefit; is the risk of taking the drug outweighed by the benefit?  Would FDA approve the RLD using today’s standards?  What changes from

505(b)(2) – Part 2: The Assessment: Efficacy Review

One of the key attractions to the 505(b)(2) route is the potential of gaining approval with only one Phase 3 study.  Moreover, this Phase 3 study is often small, at least compared to the thousands of patients in 505(b)(1) submissions.  There are exceptions, to be