Pharma shifts focus from small molecules to biologics

In the last 5 years, big pharma has continued its move toward large molecules and biologics for drug development.  Two recent studies from Withers & Rogers (a UK law firm specializing in IP) and KMR Group (a pharma consultancy) report on some of the trends among major pharmaceutical corporations during that time period.

Highlights of the W&R report include the fact that 60% of all patent filings from big pharma (top 10 companies) by 2009 covered biologics—a dramatic reshaping of a pharma IP landscape that was dominated by small molecules for as long as anyone can remember. Even though total patent filings from those companies dropped by over 30% between 2007 and 2009, biologics fillings increased by nearly 15% during the same period. Abbott is leading the way in terms of biologics IP, with large molecules accounting for 80% of its overall portfolio of recent patent filings.

The KMR report, released less than a month earlier, illustrated biologics’ higher success rates advancing to market in comparison to small molecules. The period of the KMR study was between 2006 and 2010, when 25% of large molecules in Phase II studies ultimately reached market—compared to only 10% of small molecules at the same stage.  Furthermore, KMR reported that while only 2% of small molecules advance from preclinical to clinical studies, 12% of large molecules successfully clear that critical hurdle.

The differences could be due to the fact that big pharma has been focused on small molecules for decades, and the rate of innovation in that field—particularly discoveries with blockbuster potential—has slowed dramatically.  What’s left in the pipeline is “all the low-hanging fruit…found in the last 10 to 15 years”, according to Scott Martin, a KMR consultant.

The differences—particularly in the clinic—may also be due to the generally more targeted nature of large molecule therapeutics toward disease areas where safety issues are less prevalent and it is easier to track therapeutic success (e.g., immunology, replacement therapies).  But as more and more biologics enter the research pipeline, and new applications and indications are pursued, this may change drastically in the years to come.

For more thoughts on the subject:  ThePharmaLetter… GenEngNews… PharmaField

Or contact Pearl IRB for your biologics and small molecule clinical research needs.

IOM report responds to Duke research, calls for greater “omics” oversight

In the wake of the recent commotion surrounding flawed research at Duke University on diagnostic tools based on molecular patterns (“omics” tests), an Institute of Medicine (IOM) panel has issued a report entitled Evolution of Translational Omics: Lessons Learned and the Path Forward calling for more conscientious oversight of such research and more stringent validation before it is applied in clinical trials.

In a controversy that dates back to a 2006 Nature Medicine publication by Duke researchers, headed by Dr. Anil Potti, Duke expects to retract 27 papers, has already cancelled three clinical trials, and is facing a lawsuit brought by patients of those trials.  IOM committee chair Dr. Gilbert Omenn, a computational biologist at the University of Michigan, said that the Duke scenario resulted from “a rush” to commercialize and license genomics-based tests in the clinic, adding that “there are a lot of lessons here that surely apply to other places.”.

The IOM report didn’t just find problems with Duke’s research and premature commercialization efforts; it also pointed to several problems that may be inherent to research that identifies patterns in large sets of molecules (e.g., DNA, RNA, proteins) such as omics-based testing, including “over-fitting” of data patterns due to relatively small patient sample populations, as well as the fact that the tests are so difficult to reproduce (which helps explain why so few have successfully reached the clinic). The report also specifically notes financial and institutional conflicts of interest that may have contributed to the oversight at Duke.

A recommended set of steps to more substantially validate omics tests is provided by the IOM report, which includes redundant tests from blinded samples across multiple institutions and a more proactive effort to share and review data among researchers.

For more details about the Duke case and the IOM report, see this Science article by Jocelyn Kaiser.  Or to read the full IOM report, click here.

FDA issues warning letter to clinical investigator studying marketed drugs

FDA recently issued a warning letter to clinical investigator Betty Tuller, PhD, after she purportedly violated several requirements under 21 CFR Part 312 while working at Florida Atlantic University’s Center for Complex Systems and Brain Sciences.

According to the letter, a 2011 FDA Bioresearch Monitoring Program inspection found that Tuller conducted 5 clinical studies of a marketed drug that required compliance with FDA’s Investigational New Drug (IND) regulations—despite the product’s currently-approved status.  Among the violations outlined in the inspection report and warning letter, Tuller often failed to obtain informed consent from patients, failed to maintain adequate records, and failed to properly report to an IRB.

The warning letter clearly indicates to Tuller that “by not providing the subjects under your care with the information they were entitled to receive to assist them in making an informed decision about whether to participate in the studies, you compromised the rights, safety, and welfare of those subjects… [and] the IRB was unable to make an informed determination regarding the continued safety of the subjects enrolled in your investigations.”

The lesson here is that clinical studies of approved drugs involving new administration routes or dosage levels that increase the drug’s risks significantly must adhere to FDA’s IND regulations, requirements, and submission processes. That is, oftentimes, clinical research studies involving already approved drugs that are on the market not only need proper IRB oversight, but may also need to be conducted under an IND application.

For more information about properly planning, implementing, and managing clinical drug trials, click here to read Pearl IRB’s White Papers on the subject, or contact Pearl IRB today.

St. Vincent’s Health to hold Eighth Annual Research Symposium

Save the date Wednesday June 13, 2012 for the Eighth Annual Research Symposium by St. Vincent Health.  The event will go from 7:00am-4:00pm at the Lilly Conference Center at the Marten House.  The main topics will be regulatory updates, family medicine, women’s health, and internal medicine.  To learn more, call 317-338-2194.

Case Studies Released

Pearl is excited to announce its release of several case studies.  Check out our case study section to see how Pearl offers real solutions to companies ranging from small start-ups to large multi-nationals.  To view our IRB case studes, click here.  To see the breadth of services Pearl can offer, click here.

INpact Meeting April 20th

Please join us for the April 20th, 2012 INpact meeting from 11:30AM-1:00PM in Indianapolis, Indiana.  Gretchen Bowker, Pearl Pathways COO, will serve as a panelist for the discussion.  The topic of discussion will be about the FDA 510(k) process and how it will change and affect medical device companies.  To learn more, click here.

FDA Public Hearing April 23-24, 2012

The FDA will hold a 2 day public hearing to obtain input from those interested in FDA’s scope and direction in modernizing regulations, policies, and practices that apply to clinical trials of FDA-regulated products. Anyone interested is strongly encouraged to join and give their input. The 2 day hearing will be held April 23-24, 2012 at FDA White Oak Campus from 8:30am to 4:30pm. There will also be a webcast offered. To read more about the hearing, how to gain access to the webcast, and further visitor information, click here.

New FDA Informed Consent Requirements

In February, FDA released a new guidance document entitled “Questions and Answers on Informed Consent Elements, 21 CFR § 50.25(c)”.   The purpose of the guidance is to help small businesses, particularly clinical trial sponsors, investigators, and institutional review boards (IRBs) better understand and comply with the new 21 CFR § 50.25(c) informed consent requirement, which calls for the inclusion of “a specific statement that refers to the trial’s description on www.ClinicalTrials.gov.”

Sponsors and investigators must determine whether or not a trial is applicable, which FDA describes as including “controlled interventional studies (with one or more arms) of drugs, biological products, or devices that are subject to FDA regulation, meaning that the trial has one or more sites in the United States, involves a drug, biologic, or device that is manufactured in the United States (or its territories), or is conducted under an investigational new drug application (IND) or investigational device exemption (IDE).”

For applicable trials initiated on or after March 7^th, 2012 informed consents (ICs) must now include the following statement: “A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”

For more information about clinical trial compliance or for help with consent forms, protocol review, or any other IRB services, contact PearlIRB.

Are clinical trial patients doing more harm than good?

Several sources have recently pointed to possible links between poor patient adherence during clinical drug trials and unexpected adverse effects—as well as personal injury cases—once the drug is approved and marketed.  Chief among these sources is the Consumer Health Information Corporation (CHIC), which recently posted a PRWeb article on the subject.

The CHIC release points to the work of Dr. Dorothy L. Smith, who authored, “Patient Adherence in Clinical Trials: Could there Be a Link to Postmarketing Patient Safety?”, recently published in the Drug Information Journal.  In the article, Smith summarizes 20 years of research on patient adherence in clinical trials; among her observations is the unsettling fact that up to 30% of clinical trial participants miss drug doses and/or do not take the full dose.  Smith also claims that the problem is exacerbated by patients’ failure to fully disclose the dosing issues to doctors who must evaluate the drug’s safe and effective dosing range for the general patient population.

Skipping or cutting drug doses can result in a substantial overestimation of that optimal dosing range.  Patients in the post marketing population who assume that their dosing regimen has been proven safe and effective might incur unexpected adverse effects and potentially serious pathologies due to their adherence to an overestimated dosing range.

Poor adherence can be combatted by dramatically increasing the sampling size of clinical trial participant populations; however, this can be extremely expensive (and in most cases impossible) for many sponsors, investigators, and small businesses managing clinical drug trials.

Instead, Smith and others have suggested that the solution lies in increased communication: educating the participating trial population about the critical nature of their role in the trial and their strict adherence to dosing schedules—not merely for their own health, but for the benefit of all patients who will use the drug in the future.

For help designing or managing clinical trials, contact PearlIRB.

IOM report highlights benefits of pediatric drug studies

A report released Feb. 29^th by the Institute of Medicine (IOM) provided a review of the benefits of current federal laws that offer incentives for or require drug and biologic developers to conduct pediatric studies.  The report also highlighted several areas where Congress and FDA could make better use of clinical information gleaned from pediatric studies.

Historically, pediatric studies have been infrequently implemented, due in large part to both the small sample populations available and the relatively low potential economic return for drug developers in those markets.  Clinically, many pediatricians prescribe medications approved for use in adults but not tested in children; these medications can often have different risk-benefit profiles between pediatric and adult patients.

Since 2007, Congress has taken a stronger stance on the implementation of pediatric studies, passing the Best Pharmaceuticals for Children Act (BPCA)—which offers drug developers financial incentives to conduct pediatric studies—and the Pediatric Research Equity Act (PREA)—which requires pediatric studies under certain circumstances.

The IOM report noted that these laws have had very positive effects in stimulating the implementation of pediatric studies and generating helpful information about the use of various therapies in pediatric patients.  However, the report also suggested that FDA exercise its authority more frequently to require long-term pediatric safety studies as follow-up for approved and currently marketed drugs, and that Congress extend FDA’s authority to impose sanctions and fines for unreasonably delayed pediatric studies.

To read a review of the report on MedicalExpress, click here.  To view the full IOM report, click here.  If you need help planning or managing clinical trials, contact Pearl.