My understanding is that drugs injected subcutaneously end up in bloodstream. Insulin is an example. You can deliver it topically, but how you provide hypoxic environment?
Problem is how are you going to administer Apaz for oral cancer therapy?
I don’t like an idea of buyout. I would prefer ARRY to stand alone and find a good European partner which will fund more phase 3 trials with binimetinib and encorafenub. I expect that in 3-5 years ARRY’s market cap will be in $3B to $5B range with good prospects for further growth in next 10 years.
for scientific reasons.
A Phase Ib/II Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma, NCT01801358. Quick reaction from Novartis.
Reread the paper and found under the Discussion "The major limitation of this study is the low patient number, resulting from early closure of the study because of low accrual."
Selumetinib in thyroid cancer is a small potential revenue source. Projected worldwide peak sales is about $100M, meaning ~$10M in royalty payment to ARRY. Same for uveal melanoma. Therefore, today's phase 3 failure was not a critical event for the company.
Temozolomide and dacarbazine have the same active metabolite. Dacarbazine does not require liver metabolism for activation. Clinically, dacarbazine is the only chemotherapy approved for use in the treatment
of melanoma and is the most commonly prescribed chemotherapy for both metastatic cutaneous and uveal melanoma.
EXEL has one drug on the market, Cometriq. Another drug, Cobimetinib, is under review by FDA for potential approval in November 2015.
The eye opener is a phase 3 study, SPINOZA, NCT00491491, run by Sheba Medical Center. The results are described in the article published in Cancer 2012;118:4706-14. They analyzed only 43 of 158 patients that should have been recruited in the study. It was completed in February 2015. It would be interesting to see the results obtained from 158 patients.
published in Exp Hematol Oncol. 2015 Jul 4;4:18.
Interesting, Z-BEAM and Z-BeEAM are two different regiments. The rationale to test Z-BeEAM is that availability of carmustine, a component of BEAM, became difficult. In Z-BeEAM, carmustine is replaced by bendamustine. Z stands for Zevalin.
"We met with the FDA. Based on our discussions with the FDA, we're starting another study, a Phase III study. That study is with the FDA right now. We'll shortly hear back from them. And in addition to that, we intend to file the new drug application. So that's where we are with apaziquone."
Two years passed. Why it is so difficult to start a study?
XOMA is going to partner XmetA and XmetS. Could be a substantial upfront payment.
"If it does better with PFS but not OS, I would worry about resistance"
OS data will be difficult to interpret due to crossover. All patients have the option of receiving selumetinib with or without dacarbazine at disease progression.
"As for Binimetinib, people seem to be more positive."
One reason to be positive about Bini+Enco in Braf-melanoma is that one combo of Braf+MEK inhibitors is already approved by FDA (GSK-Novartis) and another is pending approval (Roche).
"I search the clinical trials page"
Try MEK 162
Phase 2 data are solid with two-fold increase in PFS in selumetinib arm as compared with temozolomide arm. OS benefit was not clear. SUMIT trial has a different design comparing selumetinib plus dacarbazine with dacarbazine alone. Selumetinib is clearly active in uveal melanoma. There are good chances for significant increase in PFS in SEL+DAC arm which is primary endpoint of the trial. Not sure about OS though.
"The Company’s Board of Directors, including the Compensation Committee, acknowledges the advisory vote on executive compensation and is committed to making meaningful changes to executive compensation and related disclosures in consultation with compensation experts. In the past year several changes were made. Two new members were appointed to the Compensation Committee, a new chairman was appointed and the Compensation Committee Charter was revised. The Compensation Committee also retained an independent
compensation consultancy, Exequity, to conduct a competitive review of the Company’s executive compensation program. As a result, in 2014, although product revenue increased by approximately 31%, the Company’s Chief Executive Officer’s realized pay decreased by approximately 34%. In order to better align executive pay with stockholder returns, 75% of the Company’s Chief Executive Officer’s pay is at risk (annual
cash bonuses, restricted stock awards and stock option awards) with a base salary that represents only 19% of total compensation. The Board of Directors and management look forward to continuing a constructive dialogue with stockholders in the coming months."
Proposal No. 2 :
The Company’s stockholders approved the flexible settlement feature in connection with the potential conversion of the Company’s Convertible Senior Notes.
Proposal No. 4 :
The Company’s stockholders did not approve by advisory vote the executive compensation detailed in the proxy statement.