"why didn’t they wait for the Korean P2 to finish in Dec and use those results as the basis of a P3"
They need to have confirmatory data with non-Korean patients. I wouldn't start any phase 3 trial in US based on the results of phase 2 trial conducted in Korea.
An unmet medical need simply means providing a therapy when none exists or providing a new therapy that may be superior to or less toxic than an existing one. For AA, Spectrum needs to convince FDA that Poziotinib is superior to Neratinib or safer. BTW, Lapatinib, another HER inhibitor, is already approved for metastatic BC and in current Ph3 trial Puma hopes to demonstrate that Neratinib plus Capecitabine is superior to Lapatinib plus Capecitabine . What kind of data Spectrum should bring to FDA to convince them to grant AA? Why Puma did not get AA for Neratinib from FDA?
"Powering the drug for superiority" is not what company did intentionally. Current study run by Spectrum is a non-inferiority trial and it requires many patients. It happens that the number of patients in non-inferiority trial allows them to make a superiority analysis. Many other non-inferiority trials are/were powered for superiority. It is not a special design of the trial from Spectrum although from what Raj/you said it sounds like something encouraging.
Juno Therapeutics, Inc. (JUNO) today announced that it has received notice from the U.S. Food and Drug Administration (FDA) that a clinical hold has been placed on the Phase II clinical trial of JCAR015 in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia (r/r ALL), known as the “ROCKET” trial. The clinical hold was initiated after two patient deaths last week, which followed the recent addition of fludarabine to the pre-conditioning regimen.
ARRY sees N-Ras metastatic melanoma market as $60 million in US and $100 million in Europe. In US, it is about 2000 patients a year, with about three-month duration of treatment.
Pralatrexate in Combination with Bortezomib for Relapsed or Refractory Peripheral T Cell Lymphoma in 5 Elderly Patients.
Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.
One CR and one PR out of five patients translates into 40% response rate. Good results.
It was not a blinded study, patients had infusion of dacarbazine or pill of Binimetinib, obvious for everybody what arm are you in. Significant percentage of patients dropped out at a very start of study, mostly from dacarbazine arm, and switched to immunotherapy. Therefore, longer OS. FDA will consider it.
“Efficacy and Safety of Vincristine Sulfate Liposome Injection in the Treatment of Adult Acute Lymphocytic Leukemia” published in The Oncologist.
It is a nice review with three individual patient cases. There is an interesting discussion on how the patient population for Marqibo will look like when CAR-T therapy is available. Marqibo will be used for:
- patients with T-cell lineage ALL. CAR-T works only for B-cell lineage ALL
- keeping the tumor from progressing during the time needed for CAR-T cells preparation in the laboratory
- palliative treatment
"2 NDA FILING FIRST HALF OF THE YEAR". I know only about ONE NDA filing in 1H, it is for binimetinib in N-Ras melanoma. What is the second one?
Breast cancer is not immunogenic except TNBC which accounts for about 10-17% of all breast cancers. And response rates in immunotherapy are usually not higher than 20%.
Yes, it was discussed here in length. Last year, in analyst day presentation Jeffrey Vacirca said: “Obtaining superiority is not important”. It is a doctor's opinion who knows the field. I tend to agree with him. This drug will be viewed as biosimilar.
To estimate revenue from SPI-2012 you may consider the following:
1. Neulasta brought $4.6B for Amgen in 2014.
2. Biosimilars rarely take more than 30% of market share from branded drugs in Europe, where they have been commercially available since 2006. It means, all biosimilars of Neulasta could compete for $4.6B x 0.3 = $1.38B
3. Introduction of a biosimilar leads to a discount of 20% to 30% compared to the branded version. Assuming 25%, total market for biosimilars of Neulasta is $1.04B.
4. Three companies, Sandoz, Apotex and Coherus are way ahead of Spectrum in bringing Neulasta biosimilars to the market, and Teva, most likely, will be the fourth one. Assuming equal share in sales between five companies, each company could generate $200M.
5. Spectrum can hardly keep up with the marketing muscle of Teva and Sandoz. Therefore, Spectum’s slice of the pie should be less than $200M.