PFF DISEASE EDUCATION WEBINAR SERIES. Welcome!

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1 PFF DISEASE EDUCATION WEBINAR SERIES Welcome!

2 PFF DISEASE EDUCATION WEBINAR SERIES David J. Lederer, MD, MS PFF Senior Medical Advisor, Patient Communications Harold Collard, MD PFF Medical Advisory Board Member PFF Summit 2015 Chairman Eugene Sullivan, MD Principal at EJS Consulting, LLC PFF Summit 2013 Faculty

3 WEBINAR AGENDA FDA s public meeting on IPF Patient- Focused Drug Development Drug development process FDA role in drug development Q+A

4 FDA S PUBLIC MEETING ON IPF

5 FDA S PATIENT-FOCUSED DRUG DEVELOPMENT INITIATIVE Announced in April 2013 Goal is to permit a systematic approach for the Agency to obtain patients input on specific disease areas Patients perspectives on their condition The impact of a disease on daily life Available therapies Selected conditions that meet the following criteria: Chronic, symptomatic, or affect functioning and activities of daily living Disease areas for which key disease aspects are not captured in clinical trials Disease areas for which there are currently no or very few therapies Prescription Drug User Fee Act Patient-Focused Drug Development; Announcement of Disease Areas for Meetings Conducted in Fiscal Years Federal Register 70 (11 April 2013), pp

6 CONDITIONS SELECTED FOR PUBLIC MEETINGS BY THE FDA Idiopathic pulmonary fibrosis Alpha-1 antitrypsin deficiency Lung cancer Pulmonary arterial hypertension Breast cancer HIV Fibromyalgia Parkinson s and Huntington s disease Sickle cell disease Others Prescription Drug User Fee Act Patient-Focused Drug Development; Announcement of Disease Areas for Meetings Conducted in Fiscal Years Federal Register 70 (11 April 2013), pp

7 FDA S IPF MEETING September 26, 2014 FDA White Oak Campus in Silver Spring, MD Registration closes TODAY (Sept 17) FDA is requesting comments Two topics Topic 1: Disease signs, symptoms and daily impacts that matter most to patients Topic 2: Patient perspectives on current approaches to treating idiopathic pulmonary fibrosis Information about registration and the FDA s request for comments:

8 FDA S TOPIC #1 Disease signs, symptoms and daily impacts that matter most to patients 1. Of all the symptoms that you experience because of IPF, which symptoms have the most significant impact on your life? (Examples may include shortness of breath, cough, fatigue, etc.) 2. Are there specific activities that are important to you but that you cannot do at all or as fully as you would like because of your condition? (Examples of activities may include household chores, walking up the stairs, etc.) a) How do your symptoms and their negative impacts affect your daily life on the best days? On the worst days? b) How has your condition and its symptoms changed over time?

9 FDA S TOPIC #2 Patient perspectives on current approaches to treating idiopathic pulmonary fibrosis 1. What are you currently doing to help treat IPF or its symptoms? (Examples may include prescription medicines, over-the-counter products, and other therapies including non-drug therapies such as diet modification.) a) How well does your current treatment regimen treat the most significant symptoms of your disease? 2. What are the most significant downsides to your current treatments and how do they affect your daily life? (Examples of downsides may include bothersome side effects, going to the hospital for treatment, etc.) 3. Because there is no complete cure for your condition, what specific things would you look for in an ideal treatment for your condition?

10 Drug Development Process: How does a potential therapy get from the bench to the bedside?

11 IND SUBMITTED NDA SUBMITTED PRE-DISCOVERY DRUG DEVELOPMENT TAKES A LONG TIME! Developing a new medicine takes an average of years; very few potential drugs survive the clinical trial process Drug Discovery Preclinical Clinical Trials FDA Review Scale-Up to Mfg. Post-Marketing Surveillance ~ 5,000 10, COMPOUNDS ONE FDA- APPROVED DRUG PHASE 1 PHASE 2 PHASE 3 NUMBER OF VOLUNTEERS ,000 5, YEARS 6 7 YEARS YEARS INDEFINITE Sources: Drug Discovery and Development: Understanding the R&D Process, CBO, Research and Development in the Pharmaceutical Industry, 2006.

12 CLINICAL TRIAL PHASES Phase 1: Focused on finding major toxicity and tolerability issues, appropriate dose Usually small numbers of subjects Short in duration Used to determine what the drug does to the subject (pharmacodynamics) and what the subject does to the drug (pharmacokinetics)

13 CLINICAL TRIAL PHASES Phase 2: Focused on safety and tolerability, and signal of efficacy Usually larger numbers of subjects Longer in duration Used to determine if a drug is safe and provide evidence of potential efficacy

14 CLINICAL TRIAL PHASES Phase 3: Focused on proving efficacy Usually largest numbers of subjects Longest in duration Used to determine if a drug is effective! (Regulatory approval in US often requires two phase 3 trials showing efficacy)

15 Slide courtesy of Prof. Luca Richeldi PHASE 1 PHASE 2 PHASE 3 REGISTRATION LAUNCHED POSITIVE RESULTS NEGATIVE RESULTS ON GOING PENDING RESULTS

16 Slide courtesy of Prof. Luca Richeldi PHASE 1 PHASE 2 PHASE 3 REGISTRATION LAUNCHED PIRFENIDONE (EU, JAPAN, SOUTH KOREA INDIA, CHINA, CANADA, MEXICO) POSITIVE RESULTS NEGATIVE RESULTS ON GOING PENDING RESULTS

17 Slide courtesy of Prof. Luca Richeldi PHASE 1 PHASE 2 PHASE 3 AMBRISENTAN BOSENTAN REGISTRATION LAUNCHED COTRIMOXAZOLE PIRFENIDONE (EU, JAPAN, SOUTH KOREA INDIA, CHINA, CANADA, MEXICO) NAC PIRFENIDONE (US) IFN-g WARFARIN TRIPLE THERAPY SILDENAFIL NINTEDANIB POSITIVE RESULTS NEGATIVE RESULTS ON GOING PENDING RESULTS

18 Slide courtesy of Prof. Luca Richeldi PHASE 1 MACITENTAN ILOPROST BOSENTAN STX-100 AMBRISENTAN PHASE 2 PHASE 3 REGISTRATION LAUNCHED CC-930 CNTO 888 COTRIMOXAZOLE OMEPRAZOLE ETANERCEPT IMATINIB ZILEUTON PIRFENIDONE (US) PIRFENIDONE (EU, JAPAN, SOUTH KOREA INDIA, CHINA, CANADA, MEXICO) QAX576 NAC TRALOKINUMAB IFN-g POSITIVE RESULTS NEGATIVE RESULTS ON GOING PENDING RESULTS THALIDOMIDE WARFARIN TREPROSTINIL TRIPLE THERAPY BMS SILDENAFIL NINTEDANIB SIMTUZUMAB LEBRIKIZUMAB FG

19 Slide courtesy of Prof. Luca Richeldi PHASE 1 MACITENTAN PRM-151 ILOPROST BOSENTAN STX-100 hmsc AMBRISENTAN PHASE 2 PHASE 3 REGISTRATION LAUNCHED GSK CC-930 CNTO 888 SAR COTRIMOXAZOLE OMEPRAZOLE ETANERCEPT IMATINIB PIRFENIDONE (EU, JAPAN, SOUTH KOREA INDIA, CHINA, CANADA, MEXICO) NAC QAX576 LOSARTAN POSITIVE RESULTS NEGATIVE RESULTS ON GOING PENDING RESULTS ZILEUTON THALIDOMIDE PIRFENIDONE (US) TREPROSTINIL WARFARIN TRIPLE THERAPY TETRATHIOMOLYBDATE BMS SILDENAFIL NINTEDANIB SIMTUZUMAB OCTREOTIDE TRALOKINUMAB IFN-g GC1008 LEBRIKIZUMAB FG-3019 IW001

20 Drug Development Process: FDA Involvement

21 FDA: LEGAL BASIS Food, Drug and Cosmetic (FD&C) Act Law (passed by congress, signed by the president) Provides legal authority for FDA s activities FDA can only do what the FD&C Act allows Regulations FDA interprets the language of the FD&C Act and writes specific regulations Regulations have the rule of law Guidance Documents FDA uses these to communicate its current thinking to drug developers

22 FDA S PRIMARY CONCERNS 1. Protect the safety of human subjects in clinical trials 2. Advise drug developers regarding the type and amount of data that will ultimately be required to support approval of the new drug 3. Ensure that marketed drug products provide a meaningful clinical benefit to patients, and that the established benefits outweigh the risks of the product.

23 FDA S PRIMARY CONCERNS 1. Protect the safety of human subjects in clinical trials 2. Advise drug developers regarding the type and amount of data that will ultimately be required to support approval of the new drug 3. Ensure that marketed drug products provide a meaningful clinical benefit to patients, and that the established benefits outweigh the risks of the product.

24 FDA S PRIMARY CONCERNS 1. Protect the safety of human subjects in clinical trials 2. Advise drug developers regarding the type and amount of data that will ultimately be required to support approval of the new drug 3. Ensure that marketed drug products provide a meaningful clinical benefit to patients, and that the established benefits outweigh the risks of the product.

25 FDA INVOLVEMENT DURING DRUG DEVELOPMENT FDA becomes involved at the first introduction of the drug into humans design/synthesis of a new drug, testing in animal models of disease, etc. are not regulated by FDA As clinical studies proceed, FDA interacts with the developer to: 1. Protect the safety of human study subjects 2. Provide advice to the developer so that the development program will generate the data that will be needed for marketing approval

26 PROTECTION OF HUMAN STUDY SUBJECTS FDA considers topics such as: Animal testing (appropriate testing conducted, with acceptable results) Theoretical risks to study subjects Informed Consent for study subjects Exclusion of subjects at greater risk Adequacy of clinical monitoring during study Safety findings from completed and ongoing studies FDA can refuse to allow a study to be conducted (or halt an ongoing study) if it has safety concerns ( Clinical Hold )

27 ADVICE TO DEVELOPERS FDA comments on issues such as: Data to support the selected dose/frequency Types of patients to study Severity of disease, concomitant diseases / drugs, etc. Ways to assess for meaningful clinical benefit to patients Adequacy of the safety assessments Numbers of patients exposed, safety monitoring used in the studies, etc Developers are usually not required to follow FDA s advice Exception: significant safety concern

28 MARKETING APPROVAL When the developer believes it has adequate data to support approval, it submits a New Drug Application (NDA) FDA must determine that: 1. The data establish that the drug will provide a clinically meaningful benefit to patients ( feels, functions, survives ) 2. The safety profile of the drug has been adequately explored, and that the established benefits outweigh the risks FDA must agree on the text of the prescribing information ( product label ) Guides the claims that can be made about the drug

29 ONGOING SAFETY ASSESSMENT OF MARKETED DRUGS Pharmaceutical firms are required to: continue to monitor the safety of approved drugs submit periodic reports on the accumulating safety information to the FDA communicate important new safety information Depending on the data available at the time of approval, firms may be required to: conduct additional studies take specific measures to ensure the safe use of the drug

30 SUMMARY FDA s involvement in the drug development process is primarily intended to: 1. Protect the safety of human study subjects 2. Advise drug developers 3. Ensure that marketed drugs provide a meaningful clinical benefit to patients, and that the established benefits outweigh the risks

31 Q+A

32 Q+A Provide information on FDA Policy that permits patients to bring in three month s supply of unapproved drugs to treat life-threatening diseases like IPF. How does one make arrangements to do this? How are diseases prioritized for research and development? Are there any medications available now for pulmonary fibrosis on a compassionate basis for one who needs it now?

33 Q+A Why is it taking so long for FDA approval of drugs like pirfidenone that is approved in Europe, Japan and elsewhere? When can FDA approval for pirfenidone and nintedanib realistically be expected? Then how long for it to appear on the market and offered under insurances including Medicare? Has pirfenidone been shown effective for someone with advanced IPF and how is someone determined to have advanced versus moderate IPF? Is there any way at all for someone whose PF is not idiopathic to get pirfenidone?

34 Q+A Will the ones who did not meet the criteria to participate in trials be able to take the drugs when they become available? Is there a way that we can encourage researchers to collect data on whether there is evidence of familial pulmonary fibrosis among subjects when designing their studies? That seems an important opportunity that may have been missed in recent studies. Why don t my healthcare people seem to know of any medications to help me, even if they are still being studied?

35 Q+A Should persons with Pulmonary Fibrosis (in my case fibrosis is caused by Scleroderma Lung) be organ donors or tissue donors? I would like to know what research is being done to find treatments for Chronic Hypersensitivity Pneumonitis? Are there any trials I can participate in?

36 NEXT UP IN PFF DISEASE EDUCATION WEBINAR SERIES Healthcare Professional Webinar October 22, 2014 Talking with PF Patients: Truth-Telling While Maintaining Hope Patient & Caregiver Webinar November 12, 2014 Autoimmune Related Pulmonary Fibrosis

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