Dr. Gerald Crabtree Addresses Study Sites, Seeking Fast Track & Orphan Drug Status and More
Written by ι Stock Market Media Group Staff — May 13, 2013
Nuvilex, Inc. (OTCQB: NVLX) COO Dr. Gerald Crabtree is no stranger to late stage clinical trials or dealing with blockbuster therapies for cancer patients. It’s likely that is exactly why he’s the COO at the small Silver Spring, Maryland, biotech. The road that Nuvilex is currently on – preparing for a large scale Phase III clinical trial to treat advanced, inoperable pancreatic cancer using its cell encapsulation technology or “Cell-in-a-Box” combined with the cancer killing drug, ifosfamide – Dr. Crabtree is no stranger to traveling.
With a great deal of excitement surrounding this company’s technology and the amazing results it’s shown in clinical trials against advanced pancreatic cancer and in pre-clinical studies in diabetes and against mammary tumors, there are many new investors taking a look at the company. Some are new to biotechs and some are new to the Phase III clinical trials process, so as you can imagine, this is generating plenty of questions surrounding what Nuvilex must endure to begin those trials.
Stock Market Media Group, a research and content development investor relations firm, spoke extensively about the company’s upcoming trials with the COO who has had a large role in several Phase III trials including a role with the team at Bristol-Myers Squibb (NYSE: BMY) that developed the blockbuster cancer drug, Taxol. In our discussion this week Dr. Crabtree addressed some of the items that must be dealt with before a late-stage clinical trial can begin, and where Nuvilex is in that process.
It’s Time for Nuvilex, Inc. to Go Head to Head with Eli Lilly
After completing two successful independent Phase II clinical trials where the second trial confirmed the data found in the first, the company has been in a position to move forward with a large scale, Phase III trial that will allow Nuvilex to go head to head with the best current single agent treatment for late stage, inoperable pancreatic cancer which for now is Eli Lilly’s (NYSE: LLY) Gemzar. Initially, a development plan had been formulated that was centered on a late-phase clinical trial that would be conducted in the EU, Australia, Thailand and Singapore. Dr. Crabtree says this was because the Phase II trials were done in the EU, and because Singapore is the location of Austrianova Singapore, the owners and developers of the cell encapsulation technology, but now he says that plan has expanded to include the United States.
“More recently, we have come to believe that studies should also be conducted in the US as well. This change will make this a truly global trial with studies in several countries being conducted in unison. This type of strategy is used by many companies that develop not only cancer drugs, but drugs for other indications too. In this way, if the Phase III trials are successful, marketing approval could be obtained almost simultaneously throughout a large part of the world.”
Dr. Crabtree walked us through some of the major steps that are necessary to initiate and conduct the Phase III trials. He says some of the steps we’ll talk about are already in progress and others are still to be initiated, particularly for the US-based studies, and the steps are in no order of priority, but does say most of the initiatives we’ll discuss that are left undone will occur more or less concurrently.
Nuvilex Starts by Building a Bank
One obvious area that will need to be addressed in a large scale trial that uses encapsulated cells in its technology is a large bank of cells to draw from during the study. The COO agrees and says:
“The requisite number of drug-activating cells needs to be available for the encapsulation process to ensure that sufficient cells are available to conduct the trial. With this in mind, in conjunction with ViruSure GmbH, a company in Austria that specializes in the amplification of pathogen-free cells, the Master Cell Bank of cells containing high levels of the enzyme CYP2B1 which activates the drug ifosfamide that we’ll be using as the cancer drug in our study is currently being expanded. Obtaining the requisite number of cells for the Phase III trial will be one of the rate-limiting factors for trial initiation.”
An additional area that shouldn’t be a big mystery is the company securing the sites where the patients will be treated during the trial. The COO says this isn’t as easy as just selecting from a list of hospitals. Additionally, not only does the company have to identify study sites, but Dr. Crabtree says responsible oncologists at those sites must be identified.
“Already, these things are in progress for the EU, Australia, Thailand, and Singapore studies, and they still need to complete this task for the US trials.”
A Familiar Face Could Return as the Company’s PI
Dr. Crabtree turned to a few areas that may be a bit more “inside baseball” and therefore unknown to many of the investors in biotech stocks. The first is identifying a Principal Investigator (PI), and Dr. Crabtree says there may be more than one for Nuvilex’s Phase III trial.
“In our case, given the planned wide geographic distribution of the study sites for the trial, more than one PI will probably be necessary. The PI is responsible for monitoring the overall conduct of the trials in their particular area. In our case, the PIs need to be experienced (in clinical trials) individuals with an excellent background in oncology, and in particular, the treatment of pancreatic cancer. The noted gastroenterologist/oncologist, Dr. Matthius Löhr has expressed interest in serving as a PI for the EU, Australia, Singapore and Thailand studies. Dr. Löhr is the individual who served as PI for the two Phase II trials, so he is the ideal person for the PI role because he’s familiar with the cell encapsulation technology and with the use of the cell encapsulation/ifosfamide treatment in patients with advanced pancreatic cancer.”
Dr. Löhr is currently located at the famed Karolinska Institute in Sweden. Nuvilex’s COO says a PI for the US studies remains to be identified.
Another issue that must be dealt with is the necessity of “finding” suitable facilities in which the necessary encapsulation process can be done in a large enough scale to satisfy the needs of the Phase III trial.
Dr. Crabtree stated “Facilities must be identified in which the encapsulation can be done according to GMP (Good Manufacturing Practices) standards; this is an absolute requirement for drug regulatory authorities such as the FDA, before they will grant marketing approval for any treatment or drug for any indication. Currently, efforts are underway to do so, and possible sites are being examined in the Far East; these are already GMP compliant.”
Where Would a Trial be Without a Cook Book
Nuvilex will have to develop a protocol for conducting the Phase III trial which Dr. Crabtree calls a form of “cook book” for the study.
“The protocol describes things like the type of study – in our case a two-armed, randomized study comparing our treatment vs. the best available single drug treatment (currently Gemzar), patient inclusion/exclusion criteria, the “mechanics” of carrying out the trial, end points for the trial; e.g. the type of study, median survival time, one-year survival rate, to name a few of those things. The development of the protocol will involve at least members of the Company, the PI(s), regulatory authorities, and possibly other participating investigators. We have not begun this process at this time, but some of the required information can be “gleaned” from the previous Phase II studies and this information will be part of the Phase III clinical trials protocol.”
One key initiative that can make life simpler for the company during preparations for the trial is that a Contract Research Organization (CRO) must be engaged.
“The CRO will be responsible for coordinating all aspects of the conduct of the trial. For example, the CRO can assist in the identification of study sites and investigators therein, coordinate delivery of encapsulated cells and drugs to study sites, constantly monitor the daily conduct of the study, etc. The chosen CRO will be one that has international experience in conducting Phase III clinical trials in oncology. This is an important facet of the conduct of our pivotal Phase III trial. In addition, the chosen CRO should be one that has expertise in interacting with drug regulatory authorities. We are in the process of acquiring “dossiers” for possible candidate CROs.”
“Cell-in-a-Box” on the Fast Track
Dr. Crabtree says a vital item on the list is that meetings with drug regulatory authorities must be held and he says the CRO can assist in these. It will be in these meetings where the general conduct of the study, assistance in finalizing the study protocol, etc. will be discussed. In addition, the COO says some key long term designations can be hashed out in these meetings that can benefit the company in the end.
“Importantly, “orphan drug” status for the treatment will be sought from the various regulatory authorities. The orphan drug designation is given to drugs/treatments for “rare” diseases. In the US for example, the orphan drug designation can be given to a drug/treatment for diseases that are diagnosed in less than 200,000 people each year. Since about 45,000 new cases of pancreatic cancer occur each year, our treatment should qualify for orphan drug status. In the EU, the orphan drug designation is reserved for treatments for disease that occur in less than 5 out of every 10,000 people.
The granting of orphan drug status would give us 7 years of marketing exclusivity for our treatment in the US and 10 years in the EU.”
In addition, Dr. Crabtree says the company will apply to “Fast Track” the company’s treatment. According to the FDA, Fast Track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases.
Determining whether a disease is serious is a matter of judgment, but generally it’s based on whether the drug will have an impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one. AIDS, Alzheimer’s, heart failure and cancer are obvious examples of serious diseases. Nuvilex’s COO feels his company’s treatment fits the definition:
“Because the survival of patients with advanced pancreatic cancer is so very short, in spite of the most aggressive treatment, we will seek “Fast Track” status from the various regulatory authorities because our treatment will, if successful, fill an unmet medical need. If this is granted, the time taken for the entire drug approval process by regulatory authorities will be significantly shortened. In the past, the EMEA (FDA’s equivalent in the EU) has found the orphan drug designation for the treatment to be acceptable in principle.”
The FDA says that most drugs that are eligible for Fast Track designation are likely to be considered appropriate to receive a Priority Review. A Priority Review designation is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. A Priority Review means that the time it takes FDA to review a new drug application is reduced.
Finally “Investigator” meetings need to be held, and Dr. Crabtree says this is where all participating investigators will meet to discuss all aspects of the trial.
“Representatives from the chosen CRO will probably participate in these meetings. Usually these meetings are “chaired” by PIs, but this is not always the case. Given the proposed geographic distribution of the study sites/investigators, several such meetings will be necessary. At these meetings, the protocol will be discussed in detail; potential “problems” will be discussed and resolved, etc. The holding of such investigator meetings will occur near the date of the trial initiation.”
Dr. Crabtree reminds us that these initiatives are in no particular order and that those items that are not completed yet can be done concurrently and the list can come together quickly as the different pieces fall into place.