Bevacizumab Biosimilar Development Highlights Week in Cancer News

Top news of the week in oncology and cancer drug development.

FDA Approval Sought for Bevacizumab Biosimilar

A biologics license application has been submitted for ABP-215, a biosimilar version of bevacizumab, based on data from analytical, pharmacokinetic, clinical data, pharmacology, and toxicology data, according to a statement from Amgen and Allergan, the developers of the biosimilar.

A phase III study comparing ABP-215 and bevacizumab did not reveal a clinically meaningful difference between the medications as a treatment for patients with non-squamous non-small cell lung cancer.

The risk ratio for objective response rates between therapies was 0.93. The two-sided 90% confidence interval for the risk ratio was 0.80 to 1.09, which was within the boundaries for equivalence, according to findings presented at the 2016 ASCO Annual Meeting.

The FDA will assign a review timeline within 60 days of the time of submission. A standard review for the agency takes 10 months in addition to the 60-day window, placing a decision in November 2017. If expedited, a priority review would shave 4 months off this timeline.

See more http://www.onclive.com/web-exclusives/fda-approval-sought-for-bevacizumab-biosimilar

Sanofi Plans to Halt BCG Production in 2017

Sanofi, one of the manufacturers of BCG (bacille Calmette-Guerin), has announced that it will discontinue production of the live intravesical immunotherapy, which

is indicated for the treatment and prophylaxis of carcinoma in situ of the urinary bladder

. Prior to this announcement, news of a drug shortage of the vaccine in September had indicated a problem in the supply chain.

In a letter announcing the decision, Sanofi said that the company tried to restore production to maintain long-term availability of the product, but the efforts fell short. The letter states that production at the drug manufacturing facility in Canada will halt by mid-2017. BCG production concerns have plagued Sanofi since 2011, when the FDA uncovered mold infections at their manufacturing site in Canada. Merck, the other manufacturer of the vaccine, has tried to meet demands during the most recent shortage, but has been unsuccessful at meeting all of the needs. Although unfortunate, this setback increases demand for PD-L1 inhibitors, which are gaining ground in this space.

See the letter http://blogs-images.forbes.com/benjamindavies/files/2016/11/Sanofi_Announcment-e1479419038741.jpg

FDA Approves Daratumumab Triplets for Relapsed Myeloma

The FDA has approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for patients with relapsed multiple myeloma following at least 1 prior therapy, based on findings from the phase III POLLUX and CASTOR studies. In the POLLUX trial, adding daratumumab to lenalidomide and dexamethasone reduced the risk of progression or death by 63% versus lenalidomide and dexamethasone for patients with relapsed/refractory multiple myeloma.

The median PFS was not yet reached in the daratumumab arm versus 18.4 months with lenalidomide/dexamethasone alone (HR, 0.37; 95% CI, 0.27-0.52; P <.001). In the CASTOR trial, the addition of daratumumab to bortezomib and dexamethasone reduced the risk of progression or death by 61% compared with the 2 drugs alone for patients with recurrent or refractory multiple myeloma. The median PFS was not reached in the daratumumab arm compared with 7.2 months in the control group (HR, 0.39; 95% CI, 0.28-0.53; P <.0001).

See more http://www.onclive.com/web-exclusives/fda-approves-daratumumab-triplets-for-relapsed-myeloma

FDA Rejects Apaziquone for Bladder Cancer

The FDA has issued a complete response letter to Spectrum Pharmaceuticals informing the company that its new drug application for apaziquone in bladder cancer would not be approved. The final decision follows a September recommendation from the FDA’s Oncologic Drugs Advisory Committee, which voted 14 to 0 against approving apaziquone for intravesical instillation immediately following transurethral resection in patients with non-muscle invasive bladder cancer.

Spectrum has halted its ongoing phase III apaziquone program, and following discussions with the FDA, is considering a new smaller study of the treatment. When ODAC convened in September, the panel considered an NDA for apaziquone based on findings from 2 phase III trials (identified as 611 and 612), which both missed the primary endpoint of a statistically significant reduction in disease recurrence at 2 years with a single dose of apaziquone versus placebo.

After these findings, Spectrum further examined the drug through pooling analyses of the 2 trials that were not part of the initial study designs. The company reported to the panel that these analyses revealed that the impact of apaziquone may be increased based on the timing of the treatment relative to resection.

See more http://www.onclive.com/web-exclusives/fda-issues-complete-response-letter-for-apaziquone-in-bladder-cancer

Mixed Results for Momelotinib in Myelofibrosis

Outcomes were mixed for momelotinib in topline results from 2 phase III myelofibrosis trials. In the phase III SIMPLIFY-1 trial, momelotinib achieved the primary endpoint of noninferiority compared with ruxolitinib when measuring the percentage of patients with myelofibrosis who had at least a 35% reduction in spleen volume at 24 weeks (SRR24): 26.5% versus 29%, respectively (95% CI, -11.2% to 5.6%; P = .011).

However, noninferiority for momelotinib was not demonstrated for the important secondary endpoint of response rate in total symptom score (TSS) at week 24. In a second phase III trial, SIMPLIFY-2, momelotinib missed its primary endpoint of noninferiority in SSR24 for momelotinib versus best alternative therapy: 6.7% versus 5.8% (95% CI, -8.9% to 10.2%; P = .90). In the best alternative therapy arm, 88% of patients continued receiving ruxolitinib, with the remainder receiving chemotherapy, interferon, corticosteroids, other treatments, or combination regimens involving these therapies. Momelotinib met the secondary TSS endpoint in SIMPLIFY-2, as well as 1 of 3 secondary endpoints related to anemia (transfusion independence).

See more http://www.onclive.com/web-exclusives/future-of-momelotinib-in-myelofibrosis-uncertain-after-phase-iii-update

Upfront Cabozantinib Bests Sunitinib in mRCC

Cabozantinib reduced the risk of progression or death by 34% versus sunitinib as a first-line treatment for patients with metastatic renal cell carcinoma, according to results from the phase II CABOSUN trial published in the Journal of Clinical Oncology. The overall response rate was 46% versus 18% for cabozantinib versus sunitinib, respectively. In 87% of the cabozantinib arm, there was some reduction in target lesions, compared with 44% of the sunitinib cohort.

The stable and progressive disease rates were 33% versus 36% and 18% versus 26%, respectively. The median progression-free survival was 2.6 months higher with cabozantinib. The median PFS was 8.2 months (95% CI, 6.2-8.8) in the cabozantinib group compared with 5.6 months (95% CI, 3.4-8.1) in the sunitinib cohort (HR, 0.66; 95% CI, 0.46-0.95; P = .012). The median OS was 30.3 months in the cabozantinib arm versus 21.8 months in the sunitinib arm (HR, 0.80; 95% CI 0.50-1.26).

See more http://www.onclive.com/web-exclusives/firstline-cabozantinib-superior-to-sunitinib-in-mrcc