Background: Everolimus (E) is an oral inhibitor of mTOR. Tivozanib (T) is a highly potent, selective, oral inhibitor of VEGF receptors-1, -2, and -3. Preclinical data suggest antitumor activity for this combination in colorectal cancer. We therefore performed a multicenter Phase Ib trial of E + T in patients (pts) with any refractory gastrointestinal (GI) malignancy, followed by a Phase II trial of E + T in pts with refractory, metastatic colorectal cancer (mCRC). Methods: Eligibility criteria: histologically confirmed, measurable disease; ECOG PS=2; blood pressure =150/100; no venous thromboembolism within prior 6 months. Pts with mCRC must have received prior fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab and anti-EGFR antibody (if KRAS wt). E was administered once daily continuously. T was administered once daily for 3 out of every 4 weeks. The Phase Ib study in pts with any GI malignancy followed a standard 3+3 design with 3 dose levels: (1) E 5 mg/d + T 1 mg/d; (2) E 10 mg/d + T 1 mg/d; (3) E 10 mg/d + T 1.5 mg/d. The Phase II study in pts with mCRC was a non-randomized, one-stage design with a primary endpoint of progression-free survival. Results: Between 02/10-12/10, 12 pts were enrolled to the Phase Ib study. Median age, 60 (39-81) years; male, 50%; ECOG PS 0/1/2, 42/58/0%; tumor types: esophagus 1, colorectal 11 pts. Dose limiting toxicities of grade 3 fatigue and grade 3 fatigue/ dehydration occurred in 2/6 pts on dose level 3. Grade 3/4 treatment-related adverse events in =10% of pts were dehydration, fatigue, headache, hyperglycemia, hypertension, and hypophosphatemia. The phase II study proceeded at the maximally tolerated dose (MTD) of E 10 mg/d and T 1 mg/d. Between 02/11-06/11, 40 pts with mCRC were enrolled to the phase II study. All but 1 pt received prior bevacizumab. Median age, 56 (35-81) years; male, 48%; ECOG PS 0/1/2, 45/53/2%. Treatment is ongoing. Conclusions: Among pts with refractory GI malignancies, the combination of Everolimus + Tivozanib was well-tolerated with MTD of E 10 mg/d and T 1 mg/d. A phase II trial has completed enrollment using these doses of E + T in pts with refractory mCRC; safety and efficacy data will be available for presentation.

Under the terms of the agreement, the NCI and Micromet will collaborate on a series of clinical trials to evaluate the safety and efficacy of blinatumomab in patients with B-cell derived hematologic malignancies. The initial NCI-sponsored studies will explore blinatumomab’s utility as a first-line treatment for patients newly diagnosed with ALL, older patients with ALL, and patients with Waldenstrom’s macroglobulinemia. Additional studies will be designed based on the agreement of both parties

The only person you should trust for vitamin, mineral, enzyme and amino acid information is Dr. Priscilla Slagle. She has her own website where you can view the names of the companies that you can really trust.

If you have the money, the best place to get your vitamins and amino acids is from a tiny company called Montiff, run by Don Tyson, a biochemist.

I know we have preliminary data from HCV but I do not remember any HIV studies.

One more interesting note from the study is that the Vitamin D treated group had worse clinical characteristics to begin with: viral load (50% vs 42%, P < 0.01), and fibrosis score (> F2: 42% vs 19%, P < 0.001) than the controls.

Q: You guys have the ideal product for India, and there's 1.2 billion people in India.
A: So let me ask you: three years ago, would you have said that?
Q: Three years ago, you didn't have a sales operation, relationships and structure to deal with those markets.
A: Exactly! So what did I say on All Things D? I said we spent the last three years building a global company. Putting in all the infrastructure, building the relationships, building the supply channels, the infrastructure, the distribution, the manufacturing capacity, that's what we did! And we continue to grow, right? What we're setting up is for the next 10 years of BlackBerry. We just finished the first 10 years, actually closer to 12 - the first decade of BlackBerry. Now we're setting up for the next decade of BlackBerry. Right? That's what we're doing.
I think it's because we're always thinking ahead, we're always planning ahead. I think in this kind of business you have tohave a lot of planning. It's one thing to take a reference design and package it. It's another thing to build a platform that can grow with your customers' needs, that can grow with where the market is going as opposed to where the market is today. To provide that uncompromised performance for enterprise, for government, for large corporations as well as provide an experience for the consumer that's unique.

I thought the existing agents control it and not cure it. Is it possible Bavi could help with a cure and immunize the person against getting it again. What about side effects of the current regimen?

But, more so than just looking at the safety of the two drugs individually against one another, a better safety profile could allow tivo to be a preferred option in any type of combo treatment where when you are adding a few different treatment options together, safety presumably comes into play more.

If safety translates to quality of life improvement, wouldn't that be a considerable advantage?

Provided efficacy is at least comparable, and not worse, if there are significant safety advantages for tivo relative to Sutent and the rest of the competition, I would imagine a significant safety advantage could allow it to be successful commercially even without an OS advantage. The key would presumably be the magnitude of the safety differentiation

-Ribavirin monotherapy for HCV is ineffective, and the drug is only approved for use in combination with interferon.
www.hcvadvocate.org/hepatitis/factsheets_pdf/Inf%20and%20Rib_08.pdf

This raises the question of how often patients get EVRs from Ribavirin alone.

BACKGROUND & AIMS:
In the patients with chronic hepatitis C, the addition of ribavirin to interferon (IFN)-alpha significantly increases the virologic responses. Our aim was to assess the antiviral action of ribavirin on hepatitis C virus (HCV) as a function of ribavirin pharmacokinetics and to evaluate the influence of this antiviral effect on IFN-alpha efficacy.
METHODS:
Forty-five patients with chronic hepatitis C (genotype 1b) received various schedules of IFN-alpha and/or ribavirin administration. Frequent blood sampling was performed for HCV RNA kinetics and ribavirin pharmacokinetics assessment.
RESULTS:
Ribavirin monotherapy induced a significant, moderate, early, and transient viral load decrease in approximately half of the patients. The occurrence of this effect was associated with longer ribavirin clearance half-lives and higher serum ribavirin concentrations. Ribavirin antiviral effect partly reduced the rebound preceding the second IFN-alpha injection in patients receiving standard IFN-alpha 3 times per week plus ribavirin. The magnitude of the rebound was inversely related to ribavirin concentrations. These patients subsequently experienced a slow, but significant, second slope of viral decrease and cleared HCV RNA. The addition of ribavirin to daily IFN-alpha monotherapy did not have any impact on the second phase of viral decline.
CONCLUSIONS:
Ribavirin exerts a significant, moderate, and transient antiviral effect in a significant proportion of patients with chronic hepatitis C. The antiviral effect of ribavirin correlates with ribavirin pharmacokinetics and is partly responsible for the improved efficacy of the combination of standard IFN-alpha and ribavirin compared with IFN-alpha monotherapy by increasing the incidence of the initial response.

You're right, I can't, but our managment can

but it did say that Bavi achieved a virological response in HCV, and that "seems" to be important to our management. We'll see if it translates to value for shareholders.

If there is no significant difference then what was said stands

No need to use more of the drug than necessary and if a longer treatment period is needed then much less of the drug needed

They said more "pronounced", as in "strongly marked; distinct".

Why did the 0.3 mg/kg do better than the 3.0 mg/kg?

I want this company to succeed too but successes should come like the Lung Cancer trial, where it beats 50% against comparison and is on a level ground with drugs like Avastin.

And, specific to PPHM, it's important to note that bavi was worse than a comparator that may not even be around long-term given the push for all-oral HCV DAA regimens. Very hard to take this drug seriously.