Puma Biotechnology Presents Interim Results of Phase II CONTROL Trial of Neratinib in Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer at the 2017 San Antonio Breast Cancer Symposium

LOS ANGELES, CA, USA I December 6, 2017 I Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, will present updated interim results from a Phase II clinical trial of Puma’s drug neratinib at the 2017 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas. The presentation entitled, “Effects of adding budesonide or colestipol to loperamide prophylaxis on neratinib-associated diarrhea in patients with HER2-positive early stage breast cancer: the CONTROL trial,” will be presented at a poster session on December 7 at 5:00 p.m. CST. A full copy of the poster is available on the Puma Biotechnology website.

Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX® (neratinib) tablets.

The main adverse event seen to date in clinical trials of neratinib is diarrhea and, more specifically, grade 3 diarrhea. In the Phase III ExteNET trial of neratinib as extended adjuvant treatment of HER2-positive early stage breast cancer that has previously been treated with adjuvant Herceptin, 95.4% of the patients experienced all grade diarrhea and 39.8% of the patients experienced grade 3 or higher diarrhea (there was one event of grade 4 diarrhea). The CONTROL trial is an international, open-label, Phase II study investigating the use of loperamide prophylaxis with or without other agents in the reduction of neratinib-associated diarrhea that has a primary endpoint of the incidence of grade 3 diarrhea.

In the CONTROL trial, patients with HER2-positive early stage breast cancer who had completed trastuzumab-based adjuvant therapy received neratinib daily for a period of one year. The trial initially tested high dose loperamide prophylaxis given for the first 2 cycles (56 days) of treatment (12 mg on days 1-14, 8 mg on days 15-56 and as needed thereafter). The CONTROL trial was then expanded to include two additional cohorts. One cohort received the combination of loperamide and budesonide and the other cohort received the combination of loperamide plus colestipol. Budesonide is a locally acting corticosteroid that the Company believes targets the inflammation identified in a preclinical model of neratinib-induced diarrhea and colestipol is a bile acid sequestrant that the Company believes targets potential bile acid malabsorption that could result from such inflammation.

The interim analysis of the trial presented in the poster included a total of 137 patients who received neratinib plus loperamide prophylaxis, 64 patients who received neratinib plus loperamide prophylaxis for 2 cycles and budesonide for 1 cycle, and 120 patients who received neratinib plus loperamide prophylaxis for 1 cycle and colestipol for 1 cycle.

The results of the trial showed that the incidence of grade 3 diarrhea for the 137 patients who received the loperamide prophylaxis was 30.7%. For the 137 patients who received the loperamide prophylaxis, the median number of grade 3 diarrhea episodes per patient was 1 and the median cumulative duration of grade 3 diarrhea was 3 days. For the 137 patients who received loperamide prophylaxis, 20.4% discontinued neratinib due to diarrhea.

For the 64 patients who received the combination of loperamide plus budesonide, the results of the trial showed that the incidence of grade 3 diarrhea was 26.6%. The median number of grade 3 diarrhea episodes per patient was 1 and the median cumulative duration of grade 3 diarrhea was 2 days. For the 64 patients who received loperamide plus budesonide prophylaxis, 10.9% discontinued neratinib due to diarrhea.

For the 120 patients who received the combination of loperamide plus colestipol, the results of the trial showed that the incidence of grade 3 diarrhea was 10.8%. The median number of grade 3 diarrhea episodes per patient was 1 and the median cumulative duration of grade 3 diarrhea was 3 days. For the 120 patients who received loperamide plus colestipol prophylaxis, 1.7% discontinued neratinib due to diarrhea. Further information is provided in Table 1 below:

                             
    Table 1: Characteristics of Treatment-Emergent Diarrhea
                             
    Study     CONTROL     ExteNET
                Loperamide +     Loperamide +     Loperamide
          Loperamide     budesonide     colestipol     prn
          (n=137)     (n=64)     (n=120)     (n=1408)
    Diarrhea, %
    Any grade     79.6     86.0     66.7     95.4
    Grade 1     24.8     25.0     30.0     22.9
    Grade 2     24.1     34.4     25.8     32.5
    Grade 3a     30.7     26.6     10.8     39.8
    Grade 4     0     0     0     0.1
                             
    Median cumulative duration, days
    Any grade     14.0     24.0     16.0     59.0
    Grade ≥2     5.0     6.0     3.5     10.0
    Grade ≥3a     3.0     2.0     3.0     5.0
                             
    Median diarrhea episodes/patient
    Any grade     2.0     9.0     2.5     8.0
    Grade ≥2     2.0     3.0     1.0     3.0
    Grade ≥3a     1.0     1.0     1.0     2.0
                             
    Action taken, %
    Dose hold     15.3     18.8     9.2     33.9
    Dose reduction     7.3     3.1     4.2     26.4
    Discontinuation     20.4     10.9     1.7     16.8
    Hospitalization     1.5     0     0     1.4
                             
    Duration of neratinib treatment, months
    Median     11.5     11.9     3.7     11.6
                             
    a No grade 4 events in the CONTROL study; one grade 4 event in the ExteNET study.
     

Hope S. Rugo, MD, USCF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, said, “We are pleased to see the maturation of the data supporting observations of a reduction in incidence, severity and duration of neratinib-associated diarrhea with loperamide prophylaxis, loperamide plus budesonide prophylaxis or the loperamide plus colestipol prophylaxis. Along with the continued reduction in the incidence and severity of grade 3 diarrhea with neratinib, diarrhea appears to be acute, self-limiting and manageable. The addition of budesonide or colestipol to loperamide prophylaxis appears to greatly improve the tolerability of neratinib and we look forward to the completion of the colestipol cohort.”

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, “We are pleased to see the reductions in the incidence of severe neratinib-related diarrhea in the CONTROL trial when using the loperamide, loperamide plus budesonide or loperamide plus colestipol regimens. The severe diarrhea appears to become more acute, whereby it does not typically recur after the first month. We are also very encouraged by the improvements in tolerability that have been seen to date in the budesonide and the colestipol cohorts. This is a marked improvement in tolerability over what was seen in the ExteNET trial and we look forward to continuing to monitor this in the loperamide plus colestipol cohort.”

About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

About Puma Biotechnology

Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. The Company in-licenses the global development and commercialization rights to three drug candidates—PB272 (neratinib, oral), PB272 (neratinib, intravenous) and PB357. NERLYNX® (neratinib) is approved for commercial use by prescription in the United States as extended adjuvant therapy for early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy and is marketed as NERLYNX. Neratinib is a potent irreversible tyrosine kinase inhibitor that blocks signal transduction through the epidermal growth factor receptors, HER1, HER2 and HER4. Currently, the Company is primarily focused on the commercialization of NERLYNX and the continued development of its other advanced drug candidates are directed at the treatment of HER2-positive breast cancer. The Company believes that NERLYNX has clinical application in the potential treatment of several other cancers that over-express or have a mutation in HER2.

Further information about Puma Biotechnology can be found at www.pumabiotechnology.com.

SOURCE: Puma Biotechnology

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