# Presentation: 496005

## Joint Meeting of the Anti-Infective Drugs Advisory Committee and the Drug Safety and Risk Management Advisory CommitteeOpen Public MeetingDecember 14-15,  2006 

- Prabhavathi Fernandes, Ph.D.
- President and CEO
- Cempra Pharmaceuticals, Inc.
- prabha@fernandes-domain.com

## All of Us Have the Same Goals

***Success REQUIRES that we are all on the same tablet !***

**Patients**

**Pharma**** &**
** ****Biotech**

**Physicians**

**FDA**

**We all want**
**affordable antibiotics -that are safe and **
**effective against resistant bacteria**

## The Tablet is Broken

**Physicians**

**Pharma & Biotech**

**Patients**

**FDA**

** **

**There are not enough safe and effective antibiotics**

**Lack of clear guidelines to develop antibacterials makes the financial risk too high**

**The return on investment is too low**

**We need  extraordinarily safe antibiotics that are more effective than placebo**

## Using Ketek as an Example - Find the Cause of the Problem

- Using Ketek as* an Example* - Find the Cause of the Problem

**Antibiotics developed & used for serious infections**

**1940**

**Antibiotics safe**
**& effective**

**1975**

**Patients demand for antibiotics for simple “infections”**

**Increased profits from antibiotic sales for simple infections**

**Increased patient exposure –increased reporting of adverse effects**

**Pharma markets aggressively for simple infections**

**1985**

**FDA, patients & Congress**
**question use and safety of antibiotics**

- Pharma Success

- Physician & Patient comfort

- Millions of
- patients exposed

**2005**

**Patient demand and**
**pharma greed for**
**drugs for simple infections**

- Risk-Benefit?

*WHERE ARE THE MAGIC BULLETS?*

## Thoughts that Have Arisen After Ketek was Approved

- Thoughts that Have Arisen After Ketek was Approved

- Should wide-spread use be discouraged to prevent selection of resistant bacteria?
-  We are killing the goose that is laying the golden eggs
- Should FDA protect public from unnecessary exposure to antibiotics that can result in harm?
- Should patients be using so many antibiotics for simple infections?
- Should physicians be writing so many antibiotic prescriptions?
- Should pharma sales reps promote antibiotics for simple infections?

## Unrealistic Expectations

- No drug (or antibiotic) is completely safe
- Risk-benefit analysis is easier when treating serious infections
- It is *impossible* to detect every rare side effect in any-size trials- no point in increasing the clinical trial size
- Need pre-clinical toxicology, clinical safety in 1000 patients
- Need mandatory submission of  Phase IV data
*Ban on promotion* for simple infections
- Waiting to get sufficient patients with resistant bacterial infections to prove efficacy in clinical trials is like waiting until a house is on fire to buy insurance!

## Proposal for Clinical Trial Design to Demonstrate Efficacy

- For simple infections, placebo controlled trials are the only way to demonstrate that a drug is effective
- Comparator controlled trials should be used for serious or complicated  infections to demonstrate efficacy
- 200 cases tested with new drug *vs.* one of the TOP two standard-of-care antibiotics
- Non inferiority to these compounds should be approved
- Approval for “organ system” of infection (e.g. Respiratory, SSSI)
- In infectious diseases, the biomarker is isolation of the pathogen – demonstrate the pathogen and clearance
- A new antibiotic that has activity in vitro and in animal model against resistant bacteria, and has equal or even less activity as comparator antibiotics in clinical trials, should be approved for treating resistant bacteria

## Encouragement for Developing New Antibiotics

- Clear FDA guidelines to make drug development feasible
- Two adequate  (400 patients each) and comparator controlled,  non-inferiority studies for serious infections
- Approval on the ORGAN SYSTEM basis to decrease costs of multiple clinical trials
- Some diseases are rare (e.g. endocarditis) and guidelines could combine many rare, deep tissue/organ infections into one claim
- Government should provide incentives to small companies who are addressing public health needs for new antibiotics – eg. matching grants, development expense refunds, tax incentives etc.