R-PHARM Acquires IXEMPRA(R) (ixabepilone) From Bristol-Myers Squibb and Launches U.S. Commercial Operations

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| Source: R-PHARM US, LLC

PRINCETON, N.J., Aug. 17, 2015 (GLOBE NEWSWIRE) -- R-PHARM US announces the acquisition of IXEMPRA (ixabepilone) from Bristol-Myers Squibb (NYSE:BMY). IXEMPRA received marketing approval from the U.S. Food and Drug Administration in 2007 and in 18 other markets globally. IXEMPRA is indicated as monotherapy or in combination with capecitabine for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine. With the acquisition, R-PHARM US has launched its U.S. commercial operations, and it is now responsible for all activities surrounding IXEMPRA's manufacture, distribution, sales, and reimbursement. Financial terms were not disclosed.

"IXEMPRA is an important therapy in treating metastatic or locally advanced breast cancer, and we are excited to position IXEMPRA as the cornerstone of our product portfolio," stated Mark Pavao, President and Chief Executive Officer of R-PHARM US. "Advanced breast cancer patients have limited therapeutic options, and we are committed to ensuring physicians and patients have access to IXEMPRA. When we launch our sales force in October, IXEMPRA will have the support it needs in the physician's office, and we will work to ensure IXEMPRA continues to have broad formulary and reimbursement coverage."

"We are building a pharmaceutical company with innovative financing, business development and commercialization capabilities. Our strategy is to identify and acquire underserved pharmaceutical products that can become growth brands with focused and effective commercialization support in the U.S. market," commented Demetrios Kydonieus, President and Chief Business Officer of R-PHARM US. "IXEMPRA has strong brand recognition in the oncology community, and it is reflective of the type of assets we are seeking. As we begin to generate free cash flow, we will invest in development activities to expand our brands and bring innovative products to market."

OrbiMed of New York, NY, provided financial support and Dechert LLP of Washington, DC, served as legal advisor to R-PHARM US.

About R-PHARM US

R-PHARM US was founded in 2014 with the goal of acquiring and commercializing products that help patients suffering from cancer and immunology conditions. R-PHARM US is a subsidiary of R-PHARM CJSC, a vertically integrated, global pharmaceutical business with 2014 sales of $1.5B, primarily in Russia and Eastern Europe. R-PHARM's portfolio includes IXEMPRA, a chemotherapy agent approved for metastatic breast cancer, and a pipeline that includes molecules being developed for immunology and oncology indications. The most advanced pipeline asset is olokizumab, a Phase 3-ready IL-6 being developed for rheumatoid arthritis and other immunologic conditions. More information can be found at www.rpharm-us.com and www.ixempra.com.

About IXEMPRA

Indications

IXEMPRA (ixabepilone) is indicated in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated.

  • Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic setting
     
  • Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or 4 months in the metastatic setting

IXEMPRA is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.

IMPORTANT SAFETY INFORMATION

WARNING: Toxicity in hepatic impairment

IXEMPRA® (ixabepilone) in combination with capecitabine is contraindicated in patients with AST or ALT >2.5 × ULN or bilirubin >1 × ULN due to increased risk of toxicity and neutropenia-related death

In combination with capecitabine, the overall frequency of grade 3/4 adverse reactions, febrile neutropenia, serious adverse reactions, and toxicity-related deaths was greater in patients with hepatic impairment

Caution should be used when using IXEMPRA as monotherapy in patients with AST or ALT >5 × ULN. Use of IXEMPRA in patients with AST or ALT >10 × ULN or bilirubin >3 × ULN is not recommended

With monotherapy, grade 4 neutropenia, febrile neutropenia, and serious adverse reactions were more frequent in patients with hepatic impairment

Contraindications

IXEMPRA is contraindicated in patients:

  • with a known history of a severe (CTC grade 3/4) hypersensitivity reaction to agents containing Cremophor® EL or its derivatives such as polyoxyethylated castor oil
     
  • who have a baseline neutrophil count <1500 cells/mm3 or a platelet count <100,000 cells/mm3

Peripheral neuropathy

Peripheral neuropathy was common. Patients treated with IXEMPRA should be monitored for symptoms of neuropathy, such as burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, or neuropathic pain

Neuropathy occurred early during treatment; ~75% of new onset or worsening neuropathy occurred during the first 3 cycles. Patients experiencing new or worsening peripheral neuropathy may require changes in the dose or discontinuation of IXEMPRA

Neuropathy was the most frequent cause of treatment discontinuation due to drug toxicity. Caution should be used when treating patients with diabetes mellitus or preexisting peripheral neuropathy

Myelosuppression

Myelosuppression is dose-dependent and primarily manifested as neutropenia

Patients should be monitored for myelosuppression; frequent peripheral blood cell counts are recommended for all patients receiving IXEMPRA

Patients who experience severe neutropenia or thrombocytopenia should have their dose reduced. Neutropenia-related deaths occurred in 1.9% of 414 patients with normal hepatic function or mild hepatic impairment treated with IXEMPRA in combination with capecitabine. Neutropenia-related death occurred in 0.4% of 240 patients with IXEMPRA as monotherapy

Hypersensitivity reaction

Premedicate with an H1 and an H2 antagonist approximately 1 hour before IXEMPRA infusion and observe for hypersensitivity reactions (eg, flushing, rash, dyspnea, and bronchospasm)

In case of severe hypersensitivity reactions, infusion of IXEMPRA should be stopped and aggressive supportive treatment (eg, epinephrine, corticosteroids) started

Patients who experience a hypersensitivity reaction in one cycle of IXEMPRA must be premedicated in subsequent cycles with a corticosteroid in addition to the H1 and H2 antagonists, and extension of the infusion time should be considered

Pregnancy

Women should be advised not to become pregnant when taking IXEMPRA. If this drug is used during pregnancy or the patient becomes pregnant, the patient should be apprised of the potential hazard to the fetus

Cardiac adverse reactions

Caution should be exercised in patients with a history of cardiac disease. Discontinuation of IXEMPRA should be considered in patients who develop cardiac ischemia or impaired cardiac function due to reports of cardiovascular adverse reactions (eg, myocardial ischemia, supraventricular arrhythmia, and ventricular dysfunction). The frequency of cardiac adverse reactions (myocardial ischemia and ventricular dysfunction) was higher in the IXEMPRA in combination with capecitabine (1.9%) than in the capecitabine alone (0.3%) treatment group

Potential for cognitive impairment from excipients

IXEMPRA contains dehydrated alcohol USP. Consideration should be given to the possibility of central nervous system and other effects of alcohol

Adverse reactions

Monotherapy

The most common adverse reactions (>20%) reported by patients receiving IXEMPRA monotherapy were peripheral sensory neuropathy, 62% (grade 3/4:14%); fatigue/asthenia, 56% (grade 3/4:13%); myalgia/arthralgia, 49% (grade 3/4: 8%); alopecia, 48% (grade 3/4: 0%); nausea, 42% (grade 3/4: 2%); stomatitis/mucositis, 29% (grade 3/4: 6%); vomiting, 29% (grade 3/4: 1%); diarrhea, 22% (grade 3/4: 1%); and musculoskeletal pain, 20% (grade 3/4: 3%). Drug-associated hematologic abnormalities (>40%) included neutropenia, leukopenia, anemia, and thrombocytopenia. Grade 3/4 hematologic adverse reactions included neutropenia, 54%; leukopenia, 49%; anemia, 8%; and thrombocytopenia, 7%

Combination with capecitabine

The most common adverse reactions (>20%) reported by patients receiving IXEMPRA in combination with capecitabine compared to capecitabine alone, respectively, were peripheral sensory neuropathy, 65% vs. 16% (grade 3/4: 21% vs. 0%); palmar-plantar erythrodysesthesia (hand-foot) syndrome, 64% vs. 63% (grade 3/4: 18% vs.17%); fatigue/asthenia, 60% vs. 29% (grade 3/4: 16% vs. 4%); nausea, 53% vs. 40% (grade 3/4: 3% vs. 2%); diarrhea, 44% vs. 39% (grade 3/4: 6% vs. 9%); vomiting, 39% vs. 24% (grade 3/4: 4% vs. 2%); myalgia/arthralgia, 39% vs. 5% (grade 3/4: 8% vs. <1%); anorexia, 34% vs. 15% (grade 3/4: 3% vs.1%); stomatitis/mucositis, 31% vs. 20% (grade 3/4: 4% vs. 3%); alopecia, 31% vs. 3% (grade 3/4: 0% vs. 0%); abdominal pain, 24% vs. 14% (grade 3/4: 2% vs. 1%); nail disorder, 24% vs. 10% (grade 3/4: 2% vs. <1%); musculoskeletal pain, 23% vs. 5% (grade 3/4: 2% vs. 0%); and constipation, 22% vs. 6% (grade 3/4: 0% vs. <1%). Drug-associated hematologic abnormalities (>40%) with IXEMPRA in combination with capecitabine and capecitabine alone, respectively, included neutropenia, leukopenia, anemia, and thrombocytopenia. Grade 3/4 hematologic adverse reactions included neutropenia, 68% vs. 11%; leukopenia, 57% vs. 6%; anemia, 10% vs. 5%; and thrombocytopenia, 8% vs. 4%

Cremophor is a registered trademark of BASF AG.

AST = aspartate aminotransferase; ALT = alanine aminotransferase;

ULN = upper limit of normal; CTC = common terminology criteria.

Please see enclosed IXEMPRA full US Prescribing Information, including boxed WARNING regarding hepatic impairment. www.ixempra.com

IXE-00027

MEDIA CONTACT:
Juliane Snowden
Oratorium Group, LLC
646-438-9754
jsnowden@oratoriumgroup.com