E-mail the Coalition
Revised September 6, 2002
COMPANY INFORMATION
NOTE: Tibotec-Virco is a semi-independent research and development company owned by Johnson & Johnson.
Community Contact:
Lew Sibert, Director, New Products
Telephone: (813) 227-9100
Fax: (813) 223-2208
E-mail: [email protected]
Lew Sibert
1199 Shipwatch Circle
Tampa, FL 33602
1. FDA-Approved Products:
2. Products in Development:
3. Diagnostic Products
Web page: http://www.tibotec.be
Community Meeting, March 12, 2002
Meeting was held in North Carolina on March 12.
Notes (on May 16, from fading memory) by Bob Munk; additions or revisions are welcome from anyone who attended. I no longer have a participant list from this meeting.
NOTE: on March 22, Johnson & Johnson announced that it had acquired Tibotec-Virco. The press release read, in part, "In particular, this move will give Tibotec-Virco the financial stability and resources needed to develop its two anti-HIV compounds as well as to enable its drug discovery capabilities to reach their full potential. After the acquisition is completed, Tibotec-Virco will operate as a stand-alone pharmaceutical research and development business within the Johnson & Johnson family of companies." There have been no press releases or community telephone calls or meetings since this announcement.
#################
Tibotec-Virco personnel were introduced. With the merger of
Tibotec and Virco, the company has two very different lines of
activity:
* Drug discovery (candidates identified as "TMC" plus
a number) with NNRTIs and PIs under development
* Viral resistance testing, including genotyping, the AntiVirogram
(phenotype) and the Virtual Phenotype.
DRUG DISCOVERY
PowerPoint slide sets from the meeting for both TMC114
and TMC125 are available.
TMC125 is an NNRTI with good activity against HIV containing virtually all single or double resistance mutations. It is a flexible molecule which allows it to bind to the active site in the virus even when some mutations occur that deform the binding sites. Early studies in a very small number of treatment-naive patients have shown a dramatic drop in viral load within the first seven days of use. Pts. with resistance to NNRTIs also showed good response. No dramatic side effects have been noted yet.
The next step of development is a dose-ranging trial in patients with experience with all three classes of drugs. Twice-daily dosing of 400, 800, 1200, or 1600 mg of TMC125 will be tested on top of individually optimized antiretroviral therapy. The trial is split into two based on dose levels of TMC125; study C203 and C209.
TMC114 is a PI currently in pre-clinical development. It has shown very good activity against viral strains resistant to all of the current PIs.
RESISTANCE TESTING PRODUCTS:
A PowerPoint slide
set from the meeting is available.
There was a great deal of discussion about the various resistance products on the market, and the fact tha t there might be some shake-out because the total number of tests being ordered is less than had been anticipated.
There was a great deal of discussion about the complexity of the Tibotec-Virco report forms and "cut-off" values, which many find confusing - especially when different cutoffs are used for the Antivirogram and the Virtual Phenotype. It was suggested that the reports might contain too much information for some physicians, and perhaps could be simplified, with additional information provided on separate, backup pages.
There was also some discussion of planned new products related
to therapeutic drug monitoring (TDM). Steve Piscitelli, formerly
with the NIH, talked about these. The VircoPK will provide antiretroviral
drug concentrations, estimated troughs, analysis, and recommendations
for dose adjustments; and the Virco VirtualIQ will integrate drug
concentration and resistance testing using the VirtualPhenotype.
FOLLOW UP
Tibotec Virco distributed draft protocols for the TMC125-C203
and TMC125-C209 studies after the meeting for comments from community
members present, and subsequently polled attendees by e-mail for
input regarding dosing issues in general (number of pills, frequency
of dosing, etc.) that would be minimally acceptable.
See above; on March 22, Johnson & Johnson announced its acquisition of Tibotec-Virco.
No community teleconferences or meetings are currently scheduled (as of May 16).
Tibotec-Virco
Community Brunch (in conjunction with the ICAAC Conference in
Chicago)
Meeting Summary by Dawn Averitt
December 16, 2001
9:15-11:00am
Community attendees:
Dawn Averitt
Ron Baker
Ben Cheng
Polly Clayden
Chris DeChant
Yvette Delph
Howard Grossman, MD
Bob Huff
Jules Levin
Bob Munk
Gretchen Schmelz
Matt Sharp
Emmanuel Trenado
Mike Youle, MD
Thirteen community members met with Tibotec-Virco (T-V) on Sunday morning prior to ICAAC for about 2 hours. T-V's goals for the meeting were to: introduce their senior management team; explain what the merged Company would look like; provide an overview of their pipeline in both therapeutics and diagnostics, and present a plan for future community involvement and interaction.
The meeting opened with Lew Sibert, Director of New Products (and the contact for the community within T-V), describing the meeting goals/agenda and discussing T-V's guiding principles for working with the community. Brief presentations were made by both Philippe Ballero, CEO, and Rudi Pauwels, Chief Scientific Officer (and Tibotec Founder) about the merged Company and the combined T-V scientific vision. It was made clear that the two therapeutic areas T-V is most interested in and focused on at this point are HIV and Hepatitis C. Dr. Pauwels also made it clear that T-V is not interested in producing another "me too" drug - and that the T-V commitment in this area is a long-standing one. One compound will not be enough.
The remainder of the meeting consisted of a series of presentations on T-V's diagnostic products and pipeline; the therapeutic pipeline and a brief discussion on community involvement. Following is a brief synopsis of each presentation:
Resistance Testing - Alex Rinehart, Ph.D., Associate Director, Clinical Research
The cornerstone of drug development at T-V is the Virco expertise in resistance testing. Currently, T-V is supporting more than 30 international trials (about 8,000 patients) to capture samples for their extensive database and to better understand the utility and effectiveness of genotyping and phenotyping in the clinical setting. In addition, in 2001 they performed more than 22,000 commercial tests. They now have a genotype-phenotype database that contains more than 21,000 matched (both geno and pheno) samples. These matched samples are the core of the VirtualPhenotype technology. Apparently, they have more than 85,000 genotypes and 35,000 phenotypes in the database currently.
Dr. Rinehart presented results of two studies (GENPHEREX and RealVirfen) that randomized volunteers to therapy guided by actual phenotype or VirtualPhenotype. In both studies there was no difference between the two technologies, except a trend toward significance in RealVirfen on reduction of viral load favoring the VirtualPhenotype.
The community asked several questions about establishing resistance cutoffs and the clinical reliability of the already established cutoffs. T-V responded that they are working with many pharmaceutical sponsors and with stored samples to establish the cutoffs of new compounds. In addition, they are using the extensive database to weight mutations and verify assumptions rather than declare resistance based only on genotypic data.
TMC 125 - Gerben van t'Klooster, Ph.D., Global HIV Project Leader, TMC 125
TMC 125 is T-V's "next generation" NNRTI. TMC 125 has shown activity in vitro and in early phase I studies against known NNRTI resistant virus. In a 31-day in vitro study comparing the approved NNRTI's and TMC 125, all approved NNRTI's allowed virus breakthrough within the first 7 days while TMC 125 showed no viral breakthrough through Day 31. Dr. van t'Klooster presented data on two early proof-of-principle studies (TMC 125-C208 and C207 respectively); the first looking at treatment naïve volunteers and the second looking at NNRTI-failing patients with confirmed resistance to efavirenz. Both studies were 7-day studies in less than 20 patients; however, in treatment naïve's there was a mean 99% reduction in viral RNA (~2-log decrease) and in NNRTI-resistant patients there was about a 90% reduction in viral RNA (~1-log decrease) in 7 days.
The compound appears to be well tolerated with no lab abnormalities or serious AE's evident thus far. At this point, TMC 125 should be taken with food and will be dosed twice a day. T-V continues to work on additional formulations since the pill burden is fairly high.
TMC 114 - Ronald van der Geest, Ph.D., Global HIV Project Leader, PI
TMC 114 is T-V's PI candidate. Like TMC 125, this compound
shows activity against all PI-resistant viruses tested thus far.
TMC 114 is about to enter human studies. In pre-clinical animal
studies no mutagenic potential, no signs of cardiovascular abnormalities,
no other adverse pharmacological effects, and no relevant tox
findings have occurred.
T-V's next steps are to initiate dose-ranging studies, select
a solid formulation to facilitate dosing, and to initiate interaction
studies.
The community asked if metabolic parameters are being looked at with this compound and T-V said that they are. T-V was also asked if they are looking at bone parameters and they responded that they have not looked at that yet.
Therapeutic Drug Monitoring (TDM) - Steve Piscitelli, Pharm.D., Associate Director, Clinical Pharmacology
T-V is bringing two TDM products in from Virco's work in this field. The first is VircoPK, which provides antiretroviral drug concentrations, estimated troughs, analysis and recommendations. The second is Virco VirtualIQ, which integrates drug concentration with resistance testing using the VirtualPhenotype. T-V hopes to make both of these products available in 2002.
In addition, Virco plans to work to validate IQ's to improve outcomes in clinical trials, validate the nIQ (normalized IQ) concept, study IQ's for NNRTI's, and evaluate IQ's for investigational drugs.
The community asked several clarification questions about the report (which will be a single report which includes the entire VirtualPhenotype) and about turnaround time for VircoPK (which should be less than 7 days). FDA approval of this technology was discussed but the role of the FDA in this is still unclear. The AMA reimbursement Committee has apparently put VirtualPhenotype on the new technology list, which should help with reimbursement.
The meeting concluded with a brief discussion about T-V's plans to interact with the community in 2002. Lew Sibert announced T-V's intention to convene a CAB that will meet twice in 2002. He made it clear that summaries from all CAB meetings will be made available for distribution to the community at large. In addition, T-V will be assembling a contact list of interested parties to use for periodic communication and updates. Lew asked all participants to let him know who was missing from this meeting who might be interested in participating in the future.
Meeting concluded with an expectation of a first CAB meeting
before Retrovirus.