Isis Pharmaceuticals, Inc. Message Board

contd: "After review of the documents, we continue to believe there is a good likelihood of a favorable vote," noted J.P. Morgan's Geoff Meacham, according to Reuters. The review raised no new concerns about the safety and efficacy of the drug, he added. "Net-net, we would be buyers ahead of the panel."

Sentiment: Buy

continued:
The FDA review also raises questions about the difference in dose interruption/reduction and response rates for sorafenib, noting inconsistencies with other studies. And there are likely to be a number of questions regarding the small number of Americans who were included in the final data readout.
As for the OS data, Aveo has asserted that slightly more than half of the patients in the sorafenib arm went on to receive a subsequent treatment after their disease progressed, and in many cases the subsequent therapy was tivozanib. That could have skewed the survival data, according to Aveo.
The FDA review certainly didn't offer any definitive conclusions, but it cast a cloud over Aveo's shot this week. The biotech has circled its wagons around tivozanib, confidently setting the stage for a launch in the second half of this year. A negative vote this week, though, would raise serious doubts about a drug that had been getting mixed reviews from analysts.
Aveo reorganized last fall, laying off staffers as it concentrated on the regulatory process. The downsizing occurred just weeks after Leerink Swann analyst Howard Liang downgraded the stock, unconvinced that the company's argument that positive progression-free survival data could win the day at the FDA. And with other kidney cancer drugs on the market, troubling safety signals could scuttle its chances with regulators.
"In our regulatory reviews, we could not find another case where the FDA approved an agent on progression-free survival benefit that has a clear unfavorable survival trend as in tivozanib's TIVO-1 trial or a similar pivotal trial design," Liang noted at the time.
Other analysts, though, have not had the same doubts. And today's FDA review changed nothing for them.
"After review of the documents, we continue to believe there is a good likelihood of a favorable vote," noted J.P. Morgan's Geoff Meacham, according to Reuters. The review raised no new concerns about the safety and efficacy of the

Sentiment: Buy

deja vu (continued)
Tuan Ha-Ngoc, Aveo's president and chief executive, stressed that meeting the goal of a statistically significant improvement was key while calling the result "fantastic." He said the Onyx drug used for comparison performed at the high end of expectations based on prior evidence, but noted the Aveo drug met its study goal nonetheless.

"That's what matters," he said in an interview.

Specifically, the drug showed median progression-free survival of 11.9 months in the overall study population, while the Onyx drug had a 9.1-month result. Among the 70% of studied patients who didn't have prior anti-cancer therapy--a key group because these are likely real-world candidates, according to Aveo--the result was 12.7 months for the Aveo product compared with 9.1 months for the Onyx drug.

Aveo also said tivozanib had a "well-tolerated safety profile" in the company-sponsored, late-stage study, which included 517 patients. Safety results were similar to what the company saw in its prior mid-stage study, with hypertension ranking as the most commonly reported side effect. As the company's shares dropped Tuesday, Ha-Ngoc suggested the safety result was being overlooked.

But the company declined during a conference call to offer more details on that safety profile or on some other aspects of the study. Instead, the company--along with commercialization partner Astellas Pharma Inc. (ALPMY, 4503.TO) -- aims to submit detailed findings for presentation at the American Society of Clinical Oncology's conference in early June.

Aveo wants to make a big splash at the event, known as ASCO, which will draw thousands of oncologists. But to get its study accepted, the company can't release too much information ahead of time, Ha-Ngoc said. Still, Aveo did disclose the most material information, and more than some other companies in the same position, he said. He referenced a more sparse Pfizer Inc. (PFE) announcement from November on a kidney-cancer drug that company h

Sentiment: Buy

Interesting story from jan 2012, deja vu

Jan. 3, 2012, 2:43 p.m. EST
Aveo cancer treatment meets goal, but shares drop

By Jon Kamp

--Aveo says kidney-cancer treatment meets goal in late-stage study

--Company stock plunges as analysts seek more details, suggest expectations ran high

--Aveo and commercialization partner aim to show more at big cancer conference

(Updates throughout with details on study, comments from analysts and CEO.)

Drug developer Aveo Pharmaceuticals Inc. (NASDAQ:AVEO) announced positive results Tuesday in a key study for its investigational treatment for advanced kidney cancer, but its stock traded off sharply as the company butted up against lofty expectations.

Shares of the Cambridge, Mass., firm were recently down 17.1% to $14.26 despite a sharp surge in the broader market.

Aveo's drug, called tivozanib, met its main goal in a late-stage study that matched it up against Nexavar, a treatment already on the market from Onyx Pharmaceuticals Inc. (NASDAQ:ONXX) . Specifically, tivozanib showed statistically significant improvement on a measure known as progression-free survival compared with the Onyx drug.

Analysts said results were positive, although they raised questions on a conference call about whether the Onyx drug might have done better than expected, narrowing the performance gap. RBC Capital Markets suggested tivozanib "may have slightly missed the high efficacy hurdle set by the Street."

Analysts wanted more study details and forecasts on regulatory timelines than Aveo was willing to give, in part because the company doesn't want to spoil its chances to have a big role at a significant cancer conference later this year.

Tuan Ha-Ngoc, Aveo's president and chief executive, stressed that meeting the goal of a statistically significant improvement was key while calling the result "fantastic." He said the Onyx drug used for comparison performed at the high end of expectations based on prior evidence, but noted the Aveo drug met it

Sentiment: Buy

With a short interest of about 15% of the float and considering it was around $8 just a few days ago, even a split panel vote could send AVEO to well over $10 ($14 ?!)

Sentiment: Buy

$14 has a nice ring to it!

Sentiment: Buy

Dr.Lee (continued..) : The company is also developing Convivia for the treatment of acetaldehyde toxicity resulting from ALDH2 deficiency and is seeking potential partners in other Asian countries. RPTP also has a tezampanel program that targets thrombosis and intends to initiate a Phase I study in healthy volunteers by the end of calendar 2012.

Sentiment: Buy

Here's an excerpt from an interview with Think Equity analyst Dr.Lee:

Can you tell us about some other significant products in Raptor's clinical-stage pipeline?

Lee: Raptor is developing RP103 in two other indications, Huntington's disease and NASH. With potential opportunities, we believe this de-risks the development program slightly. The most advanced indication following cystinosis is Huntington's disease, a hereditary neurodegenerative disorder that negatively affects cognition and muscle coordination. The company initiated a randomized, placebo-controlled, multi-center, 18-month, 96-patient Phase II study in collaboration with CHU d'Angers in France in October 2010. This will be followed by an open-label study with all placebo patients rolling onto RP103 and all other patients continuing on drug for up to an additional 18 months. The primary endpoint is the Unified Huntington's Disease Rating Scale. We anticipate interim data release in Q2:14 (company guidance is H1:14). Given the graveyard of drug candidates that have been developed to treat Huntington's, we believe there is a low regulatory bar.

Development of RP103 in NASH, a progressive liver disease caused by inflammation and accumulation of fat and fibrous tissue in the liver, helps further diversify the development risk of the RP103 program, in our opinion. The company initiated a Phase IIb study in juvenile patients in Q2 with completion of the trial by YE:13 followed by data in Q2:14. In an open-label, uncontrolled 11-patient Phase IIa study, 7 of 11 patients demonstrated a greater than 50% reduction in ALT levels (p=0.004) while 6 of 11 reduced levels to within normal limits. The reduction in transaminase levels was largely sustained during a 6-month post-treatment monitoring phase. The company holds WW rights in this indication but intends to partner this program given the large developmental undertaking.

Sentiment: Buy

Raptor is investigating the possibility of using RP-103 as an eyedrop in order to reduce the cystine levels in the eyes of NC patients. It is also currently in Phase II/III trial for RP-103 to treat Huntington's Disease, which affects up to 30,000 people in the U.S.

Also in Raptor's pipeline is the use of RP-103/104 for the treatment of Non-alcoholic Steatopheatits (NASH), a progressive liver disease that currently is untreatable. Conviva is another Raptor drug, and its use is being investigated in the treatment of ALDH2 deficiency, a disorder that inhibits patients from metabolizing alcohol efficiently.

Sentiment: Buy

This should boost Procysbi's prospects in treating Huntington's disease, again with an orphan designation

Sentiment: Buy

Next up is Huntington's disease (Phase 2/3), again with orphan indication!!!!

Sentiment: Strong Buy

orphan status ensures 7 year exclusivity

Sentiment: Strong Buy

Analysts see annual sales for Procysbi of around $150 million. Considering that Raptor's current market cap is around $350 million, the stock may double!

This from Aveo's briefing doc:
A favorable risk-benefit prof
ile for tivozanib was demonstrated by a clinically
meaningful and statistically
significant prolongation of
PFS and improvement in ORR
over an approved VEGFR TKI, sorafenib. Tivozanib has also demonstrated antitumor
activity when used in patients follow
ing radiographic progression on sorafenib.
Tivozanib has a well-characterized and manageab
le safety profile that is distinct from
other approved TKIs. Overall, tivozanib repr
esents a valuable addition to the treatment
armamentarium for advanced RCC.

Sentiment: Buy

FDA ODAC Briefing Document
Page 2 of 13
1.
Introduction
On September 28, 2012, Aveo Pharmaceuticals subm
itted an application for tivozanib for the
treatment of advanced renal ce
ll carcinoma. This applicati
on was supported by a single Phase
3 trial, a randomized Phase 2 trial,
and an extension/crossover study.
Tivozanib is being brought to th
e ODAC to discuss the findings of the Phase 3 trial. In this
open label trial, 517 patients with
metastatic renal cell carcinoma were randomly allocated 1:1
to either tivozanib or sorafenib. The primary
endpoint was progression-
free survival (PFS) as
determined by an independent review committee
(IRC). Overall survival (OS) was a secondary
endpoint.

PFS: The analysis of PFS showed a stat
istically significant improvement in PFS
with tivozanib; HR = 0.80, p = 0.04. Median
PFS was 11.9 mos. in the tivozanib
arm and 9.1 mos. in the sorafenib arm.

Sentiment: Buy