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R-PHARM US Expands its Oncology Asset Portfolio with the Exclusive License and Distribution Rights to episil® in the United States 

PRINCETON, N.J., April 21, 2016 (GLOBE NEWSWIRE) -- R-PHARM US today announced it has obtained the exclusive license and distribution rights to commercialize episil® oral liquid in the U.S. from Camurus AB. Camurus developed episil® as a ready-to-use therapeutic option to manage and relieve the pain associated with oral lesions, including oral mucositis (OM), which results from cancer therapy and other causes. R-PHARM intends to begin marketing episil® in July 2016. Financial terms were not disclosed.

“We launched R-PHARM US commercialization activities with the acquisition of IXEMPRA (ixabepilone) from Bristol-Myers Squibb last July, establishing our commitment to patients undergoing cancer treatment,” stated Mark Pavao, President and Chief Executive Officer of R-PHARM US. “Oral mucositis is a painful side effect that may result from cancer treatment, and it has a significant impact on a patient’s quality of life and wellbeing. episil® offers patients with a convenient and effective treatment option that provides pain relief for patients suffering from oral mucositis.”

Oral mucositis is a painful inflammation and ulceration of the mucosal membranes in the mouth that can prevent a patient from eating or drinking. It occurs in 40-75 percent of patients undergoing chemotherapy and up to 100 percent of patients who undergo a bone marrow transplant1,2,3,4,5. Oral mucositis can impact a patient’s cancer treatment by requiring an unplanned break in a radiotherapy, a reduction in chemotherapy dose, or hospitalization6. episil® oral liquid has been shown to significantly reduce pain for patients suffering from oral mucositis7.

“episil® is a purposeful addition to our portfolio, as it supports our strategy to become a leading Oncology and Immunology company in the Americas,” commented Demetrios Kydonieus, President and Chief Business Officer of R-PHARM US. “We will continue to grow our portfolio as we see opportunities to provide physicians and patients with access to safe and effective therapies.”

About episil® oral liquid

episil®, for the treatment of pain associated with oral mucositis, is the first product that is supplied as a ready-to-use, pocket-sized device, helping patients maintain their quality of life while undergoing cancer therapy. The product is administered as a lipid‐based liquid that spreads on the intra‐oral mucosal surfaces and transforms to a strongly bioadhesive FluidCrystal® film that mechanically protects the sensitized and sore epithelium of the oral cavity. episil® is conveniently administered from a ready to use multi‐dose device equipped with a metered pump. Clinical studies have demonstrated episil® has the ability to effectively reduce pain following administration. episil® was developed by Camurus AB, a privately owned Swedish life science company, and R-PHARM US acquired the exclusive U.S. license and distribution rights in April 2016. It is cleared as a medical device in the United States. More information can be found at www.episil.net.

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 JSC, a vertically integrated, global pharmaceutical business with 2015 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

1 Sonis, S. T. (2004) Oral mucositis in cancer therapy. J Support Oncology, 2(3):3–8.
2 Trotti, A., Bellm, L. A., Epstein, J. B., et al. (2003) Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol, 66(3):253–262.
3 Wardley, A. M., Jayson, G. C., Swindell, R., et al. (2000) Prospective evaluation of OM in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. Br J Haematol, 110(2):292–299.
4 Fulton, J. S., Middleton, G. J., McPhail, J. T. (2002) Management of oral complications. Semin Oncol Nurs, 18(1):28–35.
5 Dodd, M. J., Miaskowski, C., Dibble, S. L., et al. (2000) Factors influencing OM in patients receiving chemotherapy. Cancer Pract, 8(6):291–297.
6 Vera-Llonch, M., Oster, G., et al. (2006) Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma. Cancer, 106(2):329–336.
7 https://www.episil.net/clinical-data/.

IXE-00027

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

Source:R-PHARM US, LLC