Perrigo Furthers Its Consumer-Focused Transformation By Divesting Its U.K. Generic Prescription Pharmaceuticals Business For £156 Million Or Approximately $195 Million

On June 19, 2020 Perrigo Company plc (NYSE; TASE: PRGO) reported that it has reached a definitive agreement to sell its U.K.-based Rosemont Pharmaceuticals business, a generic prescription pharmaceuticals manufacturer focused on liquid medicines, to a U.K.-headquartered private equity firm for £156 million or approximately $195 million in cash (Press release, Perrigo Company, JUN 19, 2020, View Source [SID1234561243]). This transaction, which was signed and closed on the same day, represents another step in Perrigo’s transformation to a consumer-focused self-care company.

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Perrigo CEO and President Murray S. Kessler commented, "We are pleased to have reached an agreement to divest Perrigo’s non-core Rosemont business and look forward to ensuring a seamless transition. This divestiture, which was accomplished at an attractive ten times adjusted operating income multiple, is an example of Perrigo’s commitment to our transformation to a consumer-focused self-care company while remaining good stewards of shareholder value. We thank the Rosemont employees for their service to Perrigo and are confident the business will do well under new ownership."

In calendar year 2019, Perrigo realized $53 million in net sales and $0.12 of adjusted diluted EPS from the Rosemont business, which was previously included in the Consumer Self-Care International segment.

Dr. Reddy’s Laboratories announces the launch of Abiraterone Acetate Tablets USP, 250 mg in the U.S. Market

On June 19, 2020 Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY, along with its subsidiaries together referred to as "Dr. Reddy’s") reported the launch of Abiraterone Acetate Tablets USP, 250 mg, a therapeutic equivalent generic version of Zytiga (abiraterone acetate) approved by the U.S. Food and Drug Administration (USFDA) (Press release, Dr Reddy’s, JUN 19, 2020, View Source [SID1234561241]).

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The Zytiga brand and generic market had U.S. sales of approximately $454 million MAT for the most recent twelve months ending in March 2020 according to IQVIA Health*.

Dr. Reddy’s Abiraterone Acetate is available in 250 mg tablets in bottle count sizes of 120.

Roche’s IPATential150 study evaluating ipatasertib in combination with abiraterone and prednisone/prednisolone met one of its co-primary endpoints

On June 19, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the phase III IPATential150 study met its co-primary endpoint of radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) and whose tumours had PTEN loss (Press release, Hoffmann-La Roche, JUN 19, 2020, View Source [SID1234561240]). In this patient group, ipatasertib in combination with abiraterone and prednisone/prednisolone provided a statistically significant reduction in the risk of disease worsening or death, compared to current standard of care (abiraterone and prednisone/prednisolone) plus placebo. The other co-primary endpoint of rPFS in the overall study population (ITT) was not met. The safety profile for the combination of ipatasertib and abiraterone was consistent with previous analyses and known risks. The results of the IPATential150 study will be presented at an upcoming medical meeting.

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While initial data are encouraging, overall survival benefit and additional secondary endpoints are not yet mature. The trial will continue until the next planned analysis and data will be shared with health authorities.

"Prostate cancer remains a leading cause of death in men worldwide and patients with metastatic castration-resistant prostate cancer can be difficult to treat," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "The early results of the IPATential150 study are encouraging in our ongoing mission to develop new treatment options for people with advanced prostate cancer."

Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT (protein kinase B), which blocks the PI3K/AKT signalling pathway – a key driver of cancer cell growth and proliferation in prostate cancer.1,2 The PI3K/AKT pathway has also been implicated in resistance to anti-androgen therapy as androgen receptor (AR) inhibition is associated with an increase in AKT pathway activation.2,3 Functional loss of the tumour suppressor protein PTEN within the tumour, seen in approximately 40-60% of mCRPC patients, results in hyperactivation of the PI3K/AKT pathway and is associated with adverse outcomes such as increased tumour grade and stage, earlier biochemical recurrence after radical prostatectomy, metastasis, prostate-cancer-specific death, and androgen-independent progression.4,5

Roche’s clinical development programme for ipatasertib focuses on tumours that are frequently found to have activation of the PI3K/AKT pathway. In addition to prostate cancer, ipatasertib is being studied in certain types of breast cancer including triple-negative breast cancer (TNBC) and hormone-receptor positive (HR+), HER2- negative breast cancer. Results are anticipated later in 2020.

About the IPATential150 study6
IPATential150 is a double-blind, placebo-controlled, randomised phase III study assessing ipatasertib in combination with abiraterone and prednisone/prednisolone, compared to placebo plus abiraterone and prednisone/prednisolone, in adult male patients with asymptomatic or mildly symptomatic, previously untreated mCRPC.

The co-primary endpoints of the study are investigator-determined rPFS in the overall study population, as well as a subpopulation whose tumours have PTEN loss, as assessed by immunohistochemistry (Ventana assay). PFS in the study is defined as the time from date of randomisation to the first occurrence of disease progression or death from any cause, whichever occurs earlier. Secondary endpoints include overall survival, safety, time to pain progression, time to initiation of cytotoxic chemotherapy and time to function deterioration.

About ipatasertib
Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT, which blocks the PI3K/AKT signalling pathway and may prevent cancer cell growth and survival.1,2

Ipatasertib is being studied in tumours that are frequently found to have activation of the PI3K/AKT pathway, including breast and prostate cancers. Clinical studies are ongoing to evaluate the efficacy and safety of ipatasertib and the opportunity it may provide to address significant unmet needs for patients with these diseases.

Ipatasertib was discovered at Genentech in partnership with Array BioPharma Inc. (acquired by Pfizer Inc. on July 30, 2019).

About metastatic castration-resistant prostate cancer (mCRPC)
Prostate cancer is the second most frequent cancer and the fifth leading cause of death in men.7 Metastatic prostate cancer refers to prostate cancer that has spread beyond the prostate to other parts of the body (metastasised).8 Although most men are cured with treatment of localised disease, recurrent or newly diagnosed metastatic disease is associated with significant morbidity and mortality.9,10,11

Primary treatment of advanced prostate cancer is androgen deprivation therapy (ADT); however, up to one-third of patients will progress despite reduction in serum testosterone levels to castrate levels (<50 ng/dL), either through surgical or medical castration.12,13 Castration-resistant prostate cancer (CRPC) is defined by disease progression, as measured by prostate specific antigen (PSA) or radiographic measures, despite adequate suppression of serum testosterone levels.14,15 Despite the current availability of life-extending therapies for mCRPC, the majority of men will die of their disease: the median life expectancy in this population is less than three years.16,17

Prostate cancer growth and survival is driven by abnormal AR signalling. In CRPC, cell growth and proliferation is also commonly driven by activation of the PI3K/AKT signalling pathway.1,2 In particular, functional loss of the tumour suppressor protein PTEN within the tumour, seen in approximately 40-60% of people with mCRPC, results in hyperactivation of the PI3K/AKT pathway.4 PTEN loss is associated with adverse outcomes such as increased tumour grade and stage, earlier biochemical recurrence after radical prostatectomy, metastasis, prostate-cancer-specific death, and androgen-independent progression.5 The PI3K/AKT pathway has also been implicated in resistance to anti-androgen therapy as AR inhibition is associated with an increase in AKT pathway activation, suggesting that the tumour compensates for the loss of one pathway with another.2,3

About Roche in prostate cancer
For more than 50 years, Roche has been developing medicines with the goal of redefining treatment in oncology. Our research and development aim is to provide effective cancer therapies through the discovery and development of novel therapeutics that target the specific molecular pathways associated with cancer. Roche is expanding into additional areas of unmet need, working to find innovative solutions for diseases such as prostate cancer, the most prevalent cancer in men and fifth leading cause of cancer-related male death worldwide.5 Roche is committed to research into genitourinary cancers, including bladder and renal cancers, and to providing life extending treatment options for these patients.

Genentech’s IPATential150 Study Evaluating Ipatasertib in Combination With Abiraterone and Prednisone/Prednisolone Met One of Its Co-Primary Endpoints

On June 19, 2020 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the Phase III IPATential150 study met its co-primary endpoint of radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) and whose tumors had PTEN loss (Press release, Genentech, JUN 19, 2020, View Source [SID1234561233]). In this patient group, ipatasertib in combination with abiraterone and prednisone/prednisolone provided a statistically significant reduction in the risk of disease worsening or death, compared to current standard of care (abiraterone and prednisone/prednisolone) plus placebo. The other co-primary endpoint of rPFS in the overall study population (intention-to-treat) was not met. The safety profile for the combination of ipatasertib and abiraterone was consistent with previous analyses and known risks. The results of the IPATential150 study will be presented at an upcoming medical meeting.

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While initial data are encouraging, overall survival benefit and additional secondary endpoints are not yet mature. The trial will continue until the next planned analysis and data will be shared with health authorities.

"Prostate cancer remains a leading cause of death in men worldwide and patients with metastatic castration-resistant prostate cancer can be difficult to treat," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "The early results of the IPATential150 study are encouraging in our ongoing mission to develop new treatment options for people with advanced prostate cancer."

Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT (protein kinase B), which blocks the PI3K/AKT signaling pathway – a key driver of cancer cell growth and proliferation in prostate cancer. The PI3K/AKT pathway has also been implicated in resistance to anti-androgen therapy as androgen receptor (AR) inhibition is associated with an increase in AKT pathway activation. Functional loss of the tumor suppressor protein PTEN within the tumor, seen in approximately 40-60% of mCRPC patients, results in hyperactivation of the PI3K/AKT pathway and is associated with adverse outcomes such as increased tumor grade and stage, earlier biochemical recurrence after radical prostatectomy, metastasis, prostate-cancer-specific death, and androgen-independent progression.

Genentech’s clinical development program for ipatasertib focuses on tumors that are frequently found to have activation of the PI3K/AKT pathway. In addition to prostate cancer, ipatasertib is being studied in certain types of breast cancer including triple-negative breast cancer (TNBC) and hormone-receptor positive (HR+), HER2- negative breast cancer. Results are anticipated later in 2020.

About the IPATential150 study

IPATential150 is a double-blind, placebo-controlled, randomized Phase III study assessing ipatasertib in combination with abiraterone and prednisone/prednisolone, compared to placebo plus abiraterone and prednisone/prednisolone, in adult male patients with asymptomatic or mildly symptomatic, previously untreated mCRPC.

The co-primary endpoints of the study are investigator-determined radiographic progression-free survival (rPFS) in the overall study population, as well as a subpopulation whose tumors have PTEN loss, as assessed by immunohistochemistry. PFS in the study is defined as the time from date of randomization to the first occurrence of disease progression or death from any cause, whichever occurs earlier. Secondary endpoints include overall survival, safety, time to pain progression, time to initiation of cytotoxic chemotherapy and time to function deterioration.

About ipatasertib

Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT, which blocks the PI3K/AKT signaling pathway and may prevent cancer cell growth and survival.

Ipatasertib is being studied in tumors that are frequently found to have activation of the PI3K/AKT pathway, including breast and prostate cancers. Clinical studies are ongoing to evaluate the efficacy and safety of ipatasertib and the opportunity it may provide to address significant unmet needs for patients with these diseases.

Ipatasertib was discovered at Genentech in partnership with Array BioPharma Inc. (acquired by Pfizer Inc. on July 30, 2019).

About metastatic prostate cancer

Prostate cancer is one of the most common types of cancers among men worldwide. According to the American Cancer Society, more than 190,000 men in the United States will be diagnosed with prostate cancer. Metastatic prostate cancer (mPC) is when the disease has spread beyond the prostate to other parts of the body (metastasized). Although most men are cured with treatment of localized disease, recurrent or newly diagnosed metastatic disease is associated with significant morbidity and mortality.

Prostate cancer cells are fueled by androgens, which are male sex hormones including testosterone. Primary treatment of advanced prostate cancer includes androgen deprivation therapy (ADT) to reduce androgen levels in the body to near castration levels. Although most patients with mPC initially respond to ADT, effective treatments are still needed for when resistance develops and disease progresses to metastatic castration-resistant prostate cancer (mCRPC). The majority of men will die of mCRPC, with a median life expectancy of less than three years.

Ultragenyx and Kyowa Kirin Announce U.S. FDA Approval of Crysvita® (burosumab) for the Treatment of Tumor-Induced Osteomalacia (TIO)

On June 19, 2020 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for rare and ultra-rare diseases, and Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company creating innovative medical solutions using the latest biotechnology, reported that the U.S. Food and Drug Administration (FDA) has approved Crysvita (burosumab) for the treatment of fibroblast growth factor 23 (FGF23)-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older (Press release, Kyowa Hakko Kirin, JUN 19, 2020, View Source [SID1234561221]). Crysvita is a human antibody that blocks excess activity of FGF23, a hormone that causes phosphate urinary excretion and suppresses active vitamin D production by the kidney.

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"For approximately half of all individuals with TIO, surgical removal of the tumors is not possible, leaving these patients with no other treatment options. The FDA approval of Crysvita marks the first treatment option that addresses the cause of the severe hypophosphatemia and osteomalacia resulting from these rare tumors," said Camille L. Bedrosian, M.D., Chief Medical Officer of Ultragenyx. "We plan to leverage our experience and existing infrastructure with Crysvita in X-linked hypophosphatemia to bring this important medicine to patients living with the rare, painful and debilitating disorder of TIO."

"Since its approval, Crysvita has meant a great deal to patients and families that previously had no other treatment options. We are proud of the work that has been done to advance this discovery from our labs, through a robust clinical research program, and through the FDA’s priority review process, to make this treatment available to patients with TIO," said Gary Zieziula, President, North America for Kyowa Kirin. "Our commitment to meeting the needs of patients with rare and serious diseases remains steadfast and we will continue to partner with the Ultragenyx team to address these needs with urgency."

TIO is a rare disease caused by typically benign, slow-growing tumors that produce excess levels of FGF23, which is involved in phosphate reabsorption. Patients with TIO can experience

symptoms including severe hypophosphatemia (low levels of phosphate in the blood), osteomalacia (softening of the bones), muscle weakness, fatigue, bone pain and fractures. There are an estimated 500 to 1,000 people in the United States with TIO, and approximately half of all cases are believed to be inoperable. In patients for whom the tumor or lesion is inoperable, the current treatment consists of oral phosphate and/or active vitamin D replacement. Efficacy of this management is often limited, and its benefits must be balanced with monitoring for potential risks.

This is the second FDA-approved indication for Crysvita, which was first approved in April 2018 for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients one year of age and older. The XLH indication was expanded in September 2019 to include infants as young as six months of age.

The FDA approval of Crysvita for TIO was based on data from two single-arm Phase 2 studies, a 144-week study in 14 adult patients conducted by Ultragenyx in the United States and an 88-week study in 13 adult patients conducted by Kyowa Kirin in Japan and South Korea. In both studies, Crysvita was associated with increases in serum phosphorus and serum 1,25-dihydroxyvitamin D levels. Increased phosphate levels led to improvements in osteomalacia. Additionally, whole body bone scans demonstrated reduced tracer uptake with long-term treatment suggesting healing of bone lesions. Most common adverse reactions (>10%) in TIO patients are: tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache.

The FDA granted Priority Review designation for the supplemental BLA for TIO, which is reserved for drugs that treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness.

To support access, Ultragenyx has a program called UltraCare, which helps patients and caregivers understand insurance coverage and assists them in finding financial support for Ultragenyx medicines including Crysvita, and for the administration of them. Dedicated in-house UltraCare Guides are available Monday through Friday from 9 a.m. to 8 p.m. Eastern Time at 888-756-8657.

About Crysvita
Crysvita (burosumab-twza) is a recombinant fully human monoclonal IgG1 antibody, discovered by Kyowa Kirin, against the phosphaturic hormone FGF23. FGF23 is a hormone that reduces serum levels of phosphorus and active vitamin D by regulating phosphate excretion and active vitamin D production by the kidney. Phosphate wasting in TIO and other hypophosphatemic conditions, including XLH, is caused by excessive levels and activity of FGF23. Crysvita is designed to bind to and thereby inhibit the biological activity of FGF23. By blocking excess FGF23 in patients with TIO and XLH, Crysvita is intended to increase phosphate reabsorption from the kidney and increase the production of active vitamin D, which enhances intestinal absorption of phosphate and calcium.

Crysvita is approved by the U.S. FDA for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients six months of age and older and FGF23-related hypophosphatemia in

tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older, and by Health Canada and Brazil’s National Health Surveillance Agency (ANVISA) for the treatment of XLH in adult and pediatric patients one year of age and older. In Japan, it is approved by the Ministry of Health, Labor and Welfare (MHLW) for the treatment of FGF23-related hypophosphatemic rickets and osteomalacia. In Europe, Crysvita has received European conditional marketing authorization for the treatment of XLH with radiographic evidence of bone disease in children 1 year of age and older and adolescents with growing skeletons, and an application for the expanded use in adults with XLH is currently under review by the European Medicines Agency.

Kyowa Kirin and Ultragenyx have been collaborating in the development and commercialization of Crysvita globally based on the collaboration and license agreement between the parties.

U.S. INDICATION

Crysvita (burosumab-twza) is a fibroblast growth factor 23 (FGF23)-blocking antibody indicated for the treatment of:

X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.

FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

With oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol).

When serum phosphorus is within or above the normal range for age.

In patients with severe renal impairment or end stage renal disease.

WARNINGS AND PRECAUTIONS

Hypersensitivity

Discontinue Crysvita if serious hypersensitivity reactions occur and initiate appropriate medical treatment.

Hyperphosphatemia and Risk of Nephrocalcinosis

For patients already taking Crysvita, dose interruption and/or dose reduction may be required based on a patient’s serum phosphorus levels.

Patients with TIO who undergo treatment of the underlying tumor should have dosing interrupted and adjusted to prevent hyperphosphatemia.

Injection Site Reactions

Discontinue Crysvita if severe injection site reactions occur and administer appropriate medical treatment.

ADVERSE REACTIONS

Pediatric XLH Patients

Adverse reactions reported in 10% or more of Crysvita-treated pediatric XLH patients across all studies are: pyrexia, injection site reaction, cough, vomiting, pain in extremity, headache, tooth abscess, dental caries, diarrhea, vitamin D decreased, toothache, constipation, myalgia, rash, dizziness, and nausea.

Post-marketing experience reported in pediatric XLH patients receiving Crysvita – blood phosphorus increased.

Adult XLH Patients

Adverse reactions reported in more than 5% of Crysvita-treated adult XLH patients and in at least 2 patients more than placebo in one study are: back pain, headache, tooth infection, restless legs syndrome, vitamin D decreased, dizziness, constipation, muscle spasms, and blood phosphorus increased.

Spinal stenosis is prevalent in adults with XLH, and spinal cord compression has been reported. It is unknown if Crysvita therapy exacerbates spinal stenosis or spinal cord compression.

Adult TIO Patients

Adverse reactions reported in more than 10% of Crysvita-treated adult TIO patients in two studies are: tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache.

USE IN SPECIFIC POPULATIONS

There are no available data on Crysvita use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Serum phosphorus levels should be monitored throughout pregnancy. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at
1-888-756-8657.

There is no information regarding the presence of Crysvita in human milk or the effects of Crysvita on milk production or the breastfed infant.

PATIENT COUNSELING INFORMATION

Advise patients not to use any oral phosphate and/or active vitamin D analog products.

Instruct patients to contact their physician if hypersensitivity reactions, injection site reactions, and restless leg syndrome induction or worsening of symptoms occur.