Halozyme Therapeutics (HALO) is one to watch as the company is targets a substantial improvement in the growing diabetic market space, plus multiple clinical data milestones in the near future.
The company has just announced that the Phase 3 HannaH trial, conducted by Roche (RHHBY.PK), showed that women with HER2-positive early breast cancer who received a new, investigational subcutaneous (SC) injection of Herceptin® (trastuzumab), experienced comparable results to Herceptin given as an intravenous (IV) infusion. The SC administration takes around 5 minutes to administer whereas the IV formulation (the current standard) takes around 30 minutes to infuse. Since the subcutaneous administration is an injection under the skin it may allow patients to spend less time in hospital receiving their treatment versus the intravenous method. The ready to use formulation may also significantly reduce pharmacy time as no medicine preparation time is required.
"We are very pleased to see this important program achieve success in a Phase 3 pivotal clinical trial," said Gregory Frost, Ph.D., Halozyme's president and CEO. "The convenience of subcutaneous administration may provide another option for women living with early breast cancer."
Why is this announcement important to HALO shareholders? Because the company has key partnerships with Roche to apply Enhanze technology to Roche's biological therapeutics, including Herceptin(R) and MabThera(R), and with Baxter BioScience to apply Enhanze technology to immunoglobulin. Halozyme's Ultrafast Insulin program combines its rHuPH20 enzyme with mealtime insulins, which may produce more rapid absorption, faster action, and improved glycemic control.
Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I—III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial
Dr Gustavo Ismael MD a Corresponding AuthorEmail Address, Roberto Hegg MD b, Susanne Muehlbauer PhD c, Dominik Heinzmann PhD c, Bert Lum PharmD d, Sung-Bae Kim MD e, Tadeusz Pienkowski MD f, Mikhail Lichinitser MD g, Vladimir Semiglazov MD h, Bohuslav Melichar MD i, Prof Christian Jackisch MD j
A subcutaneous formulation of trastuzumab has been developed, offering potential improvements in patient convenience and resource use compared with the standard intravenous infusion of the drug. We compared the pharmacokinetic profile, efficacy, and safety of the subcutaneous and intravenous formulations in patients with HER2-positive early breast cancer.
The HannaH study was a phase 3, randomised, international, open-label, trial in the (neo)adjuvant setting. Patients with HER2-positive, operable, locally advanced or inflammatory breast cancer were randomly assigned to eight cycles of neoadjuvant chemotherapy administered concurrently with trastuzumab every 3 weeks either intravenously (8 mg/kg loading dose, 6 mg/kg maintenance dose) or subcutaneously (fixed dose of 600 mg); 1:1 ratio. Chemotherapy consisted of four cycles of docetaxel (75 mg/m2) followed by four cycles of fluorouracil (500 mg/m2), epirubicin (75 mg/m2), and cyclophosphamide (500 mg/m2), every 3 weeks. After surgery, patients continued trastuzumab to complete 1 year of treatment. Coprimary endpoints were serum trough concentration (Ctrough) at pre-dose cycle 8 before surgery (non-inferiority margin for the ratio between groups of 0·80) and pathological complete response (pCR; non-inferiority margin for the difference between groups of −12·5%), analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT00950300.
299 patients were randomly assigned to receive intravenous trastuzumab and 297 to receive subcutaneous trastuzumab. The geometric mean presurgery Ctrough was 51·8 μg/mL (coefficient of variation 52·5%) in the intravenous group and 69·0 μg/mL (55·8%) in the subcutaneous group. The geometric mean ratio of Ctrough subcutaneous to Ctrough intravenous was 1·33 (90% CI 1·24—1·44). 107 (40·7%) of 263 patients in the intravenous group and 118 (45·4%) of 260 in the subcutaneous group achieved a pCR. The difference between groups in pCR was 4·7% (95% CI −4·0 to 13·4). Thus subcutaneous trastuzumab was non-inferior to intravenous trastuzumab for both coprimary endpoints. The incidence of grade 3—5 adverse events was similar between groups. The most common of these adverse events were neutropenia (99 [33·2%] of 298 patients in the intravenous group vs 86 [29·0%] of 297 in the subcutaneous group), leucopenia (17 [5·7%] vs 12 [4·0%]), and febrile neutropenia (10 [3·4%] vs 17 [5·7%]). However, more patients had serious adverse events in the subcutaneous group (62 [21%] of 297 patients) than in the intravenous group (37 [12%] of 298); the difference was mainly attributable to infections and infestations (24 [8·1%] in the subcutaneous group vs 13 [4·4%] in the intravenous group). Four adverse events led to death (one in the intravenous group and three in the subcutaneous group), all of which occurred during the neoadjuvant phase. Of these, two—both in the subcutaneous group—were deemed to be treatment related