On February 6, 2018 Celgene Corporation (NASDAQ: CELG) reported that the Phase III, randomized, open-label, international clinical study, OPTIMISMM, achieved its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for the pomalidomide arm versus the comparator arm (Press release, Celgene, FEB 7, 2018, View Source [SID1234523791]).

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OPTIMISMM evaluated the efficacy and safety of POMALYST/IMNOVID (pomalidomide) plus bortezomib and low-dose dexamethasone (PVd) versus bortezomib and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma. It is the only phase III trial to investigate a triplet combination in patients who have all received prior lenalidomide (REVLIMID), a population for which there is a growing unmet medical need.

"The OPTIMISMM results confirm the expanding role of pomalidomide in previously treated multiple myeloma patients," said Paul Richardson, M.D., Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at the Dana Farber Cancer Institute, RJ Corman Professor of Medicine, Harvard Medical School and principal investigator of the study. "We see the PVd combination as an important step in improving care, and especially for patients previously treated with lenalidomide in this setting."

In the study, the safety profile was consistent with previously reported data. Detailed data from OPTIMISMM will be presented at future medical meetings.

The combination of POMALYST/IMNOVID, bortezomib and low-dose dexamethasone is not currently approved for use.

About POMALYST/IMNOVID

Indication

POMALYST (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment.

Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.

POMALYST is only available through a restricted distribution program called POMALYST REMS.

Venous and Arterial Thromboembolism

Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.

CONTRAINDICATIONS

Pregnancy: POMALYST can cause fetal harm and is contraindicated in females who are pregnant. If POMALYST is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS

Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm.

Blood Donation: Patients must not donate blood during treatment with POMALYST and for 1 month following discontinuation of POMALYST therapy because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST.

POMALYST REMS Program: See Boxed WARNINGS

Prescribers and pharmacies must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive POMALYST. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements.

Further information about the POMALYST REMS program is available at www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436.

Venous and Arterial Thromboembolism: See Boxed WARNINGS. Patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.

Increased Mortality with Pembrolizumab: In clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Hematologic Toxicity: Neutropenia (46%) was the most frequently reported Grade 3/4 adverse reaction in patients taking POMALYST in clinical trials, followed by anemia and thrombocytopenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.

Hypersensitivity Reactions: Angioedema and severe dermatologic reactions have been reported. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe dermatologic reactions, and do not resume therapy.

Dizziness and Confusional State: In patients taking POMALYST in clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4). Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice.

Neuropathy: In patients taking POMALYST in clinical trials, 18% experienced neuropathy (2% Grade 3 in one trial) and 12% peripheral neuropathy.

Second Primary Malignancies: Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.

Tumor Lysis Syndrome (TLS): TLS may occur in patients treated with POMALYST. Patients at risk are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.

ADVERSE REACTIONS

Nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). The most common adverse reactions (≥15%) included neutropenia (51.3%), fatigue and asthenia (46.7%), upper respiratory tract infection (31%), thrombocytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), constipation (21.7%), back pain (19.7%), cough (20%), pneumonia (19.3%), bone pain (18%), edema peripheral (17.3%), peripheral neuropathy (17.3%), muscle spasms (15.3%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15%) included neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

DRUG INTERACTIONS

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. Consider alternative treatments. If a strong CYP1A2 inhibitor must be used, reduce POMALYST dose by 50%.

USE IN SPECIFIC POPULATIONS

Pregnancy: See Boxed WARNINGS. If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a POMALYST pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436.

Lactation: There is no information regarding the presence of pomalidomide in human milk, the effects of POMALYST on the breastfed infant, or the effects of POMALYST on milk production. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from POMALYST, advise a nursing woman to discontinue breastfeeding during treatment with POMALYST.

Pediatric Use: Safety and effectiveness have not been established in pediatric patients.

Geriatric Use: No dosage adjustment is required for POMALYST based on age. Patients >65 years of age were more likely than patients ≤65 years of age to experience pneumonia.

Renal Impairment: Reduce POMALYST dose by 25% in patients with severe renal impairment requiring dialysis. Take dose of POMALYST following hemodialysis on hemodialysis days.

Hepatic Impairment: Reduce POMALYST dose by 25% in patients with mild to moderate hepatic impairment and 50% in patients with severe hepatic impairment.

Smoking Tobacco: Advise patients that smoking may reduce the efficacy of POMALYST. Cigarette smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.

On February 7, 2018 GSK reported improvements in sales, margins and cash flow in 2017 (Press release, GlaxoSmithKline, FEB 7, 2018, View Source [SID1234523795]).

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Total EPS 31.4p, +67% AER, +36% CER; Adjusted EPS 111.8p, +11% AER, +4% CER

2017 financial highlights

Turnover £30.2 billion, +8% AER, +3% CER

Sales growth across all 3 businesses: Pharmaceuticals £17.3 billion, +7% AER, +3%, CER; Vaccines £5.2 billion, +12% AER, +6% CER; Consumer Healthcare £7.8 billion, +8% AER, +2% CER

Improved Adjusted Group operating margin of 28.4% (2016: 27.5%). Pharmaceuticals 34.3%; Vaccines 31.9%; Consumer Healthcare 17.7%

Total EPS 31.4p, after accounting charges of £1.6 billion related to US tax reform

Adjusted EPS 111.8p, +11% AER, +4% CER, in line with 2017 guidance

2017 free cash flow of £3.4 billion (2016: £3.0 billion)

23p dividend declared for quarter; 80p for 2017

2018 financial guidance

2018 Adjusted EPS Guidance: Growth is subject to uncertainty of timing and impact of possible generic competition to Advair in the US:

In the event of no substitutable generic competitor to Advair in the US, expect 2018 Adjusted EPS growth to be 4 to 7% CER

In the event of a mid-year introduction of a substitutable generic competitor to Advair in the US, expect full year 2018 US Advair sales of around £750 million at CER (US$1.30/£1) with Adjusted EPS flat to down 3% CER

Both scenarios reflect the benefit of US tax reform with expected 2018 effective tax rate on Adjusted profits of 19-20%

Continue to expect 80p dividend for 2018

Product and pipeline highlights

New product sales of £6.7 billion, +51% AER, +44% CER, driven by strong performances from Tivicay and Triumeq in HIV, the inhaled Ellipta portfolio and Nucala in Respiratory and meningitis vaccines

Three key approvals: Shingrix vaccine for shingles; Trelegy Ellipta, once-daily single inhaler triple therapy for COPD; Juluca (dolutegravir and rilpivirine), first 2-drug regimen, once-daily, single pill for HIV

Preferential recommendation for Shingrix received from US CDC

Trelegy Ellipta approved in Europe for COPD

Nucala filed in US for eosinophilic COPD

Phase III HIV treatment study initiated investigating long-acting 2-drug regimen of cabotegravir plus rilpivirine administered every two months

In Oncology, Breakthrough Therapy Designation received from FDA for BCMA antibody-drug conjugate for relapsed and refractory multiple myeloma. Positive BCMA data presented at ASH (Free ASH Whitepaper) meeting.

Emma Walmsley, Chief Executive Officer, GSK said:

"In 2017 GSK delivered encouraging results from across the company with sales growth in each of our three global businesses, an improved Group operating margin, Adjusted EPS growth of 4% (CER) and stronger free cash flow.

"We are focused on competing effectively across our current portfolio and delivering three new launches which bring significant benefits to patients: Trelegy Ellipta which provides three medicines in a single inhaler to treat COPD; Juluca, the first 2-drug regimen, once-daily, single pill for HIV, helping to reduce the amount of medicines needed, and Shingrix, our new vaccine which represents a new standard for the prevention of shingles.

"Improving our Pharmaceuticals business remains our main priority and we are strengthening our pipeline with a focus on priority assets in two current therapy areas, Respiratory and HIV, and two potential areas, Oncology and Immuno-inflammation. We will provide a further update to investors at Q2 on our plans for R&D.

"We continue to make changes across GSK to drive improvements in performance and we have made several new appointments to key leadership positions.

"Looking ahead, in 2018 we could see a potential generic version of Advair in the US and our 2018 guidance reflects this. With the sales momentum we anticipate from new and recent launches and focused improvements in operating performance we are increasingly confident in our ability to deliver mid to high single digit growth in Adjusted EPS CAGR (2016-2020 at 2015 CER).

"Cash generation also continues to be a key focus with free cash flow for the year improving to £3.4 billion. We met our commitment to pay a total dividend of 80p for 2017 and continue to expect to pay 80p for 2018.

"Finally, I would like to thank all our customers, suppliers and employees for their support and hard work in 2017 and look forward to working with them in 2018 and beyond to deliver our strategic priorities and improved performance for GSK."

2018 guidance

The Group expects to make continued progress in 2018, although the expectation for Adjusted EPS growth is impacted by a number of factors including, in particular, uncertainties relating to the timing and extent of potential generic competition to Advair in the US.

In the event that no substitutable generic competitor to Advair is introduced to the US market in 2018, the Group expects 2018 Adjusted EPS growth of 4 to 7% at CER. This is based on an expected decline in 2018 US Advair sales of 20-25% at CER.

In the event of a mid-year introduction of a substitutable generic competitor to Advair in the US, the Group expects full year 2018 US Advair sales of around £750 million at CER (US$1.30/£1), with Adjusted EPS flat to down 3% at CER.

The effective tax rate for 2018 is expected to be approximately 19-20% of Adjusted profits after the impact of US tax reform which is expected to benefit the Group effective tax rate by two to three percentage points.

GSK is not able to give guidance for Total results as it cannot reliably forecast certain material elements of our Total results such as the future fair value movements on contingent consideration and put options. It should be noted that contingent consideration cash payments are made each quarter primarily to Shionogi by ViiV Healthcare which reduce the balance sheet liability and are hence not recorded in the income statement. An explanation of the acquisition-related arrangements with ViiV Healthcare, including details of cash payments to Shionogi, is set out on page 59.

If exchange rates were to hold at the average rates for January 2018 ($1.39/£1, €1.13/£1 and Yen 154/£1) for the rest of 2018, the estimated negative impact on full-year 2018 Sterling turnover growth would be around 4% and if exchange gains or losses were recognised at the same level as in 2017, the estimated negative impact on 2018 Sterling Adjusted EPS growth would be around 6%.

US tax reform

The enactment of the US Tax Cuts and Jobs Act in December 2017 is expected to have a positive impact on the future after tax earnings of GSK’s US businesses. This is primarily due to the reduction in Federal corporation tax rates from 1 January 2018, which is expected to benefit the Group effective tax rate on Adjusted profits in 2018 by two to three percentage points.

The implementation of the new law has resulted in a number of additional charges in 2017, which reduced Total earnings by £1,630 million.

Firstly, increased valuations of the HIV and Consumer Healthcare businesses due to lower US tax rates resulted in an increase in the related liabilities for contingent consideration and the put options of £666 million.

Secondly, an additional tax charge of £1,078 million comprised a reduction in the value of US deferred tax assets held against future liabilities, such as pensions, of £730 million, and a charge of £348 million arising on the reserves of subsidiaries of US entities in the Group. The cash impact of this latter charge will be spread over eight years from 2018, with approximately 60% expected to be payable in years six to eight.

These charges were partly offset by an allocation to non-controlling interests amounting to £114 million, as many of the adjustments related to ViiV Healthcare and the Consumer Healthcare Joint Venture.

These charges represent management’s estimates of the impact of US tax reform on the Group based on the information currently available. As more information on the detailed application of the Act becomes available, the assumptions underlying these estimates could change, with consequent adjustments to the charges taken that could have a material impact on the results of the Group.

On February 7, 2018 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that results from a large 1,162 patient study of the Myriad myRisk Hereditary Cancer test will be featured during the poster presentation at the 2018 Genitourinary Cancer Symposium in San Francisco, Calif (Press release, Myriad Genetics, FEB 7, 2018, View Source [SID1234523799]). The key finding is that more than 12 percent of men with prostate cancer had an inherited (i.e. hereditary) mutation in a cancer-causing gene.

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"As one of the largest studies of hereditary cancer risk assessment ever conducted in prostate cancer, our myRisk Hereditary Cancer test demonstrated that roughly the same percentage of men with prostate cancer carry hereditary cancer-causing mutations as do women with breast cancer," said Johnathan Lancaster, M.D., Ph.D., chief medical officer, Myriad Genetics. "These compelling findings provide a strong reason for expanding the use of genetic testing in men diagnosed with prostate cancer consistent with existing professional medical guidelines."

The key data are summarized below and the abstract is available at: abstracts.asco.org. Follow Myriad on Twitter via @MyriadGenetics and stay informed about symposium news and updates by using the hashtag #GU18.

Title: Inherited Germline Mutations in Men with Prostate Cancer.
Presenter: Robert Reid, M.D., Virginia Cancer Specialists.
Date: Sunday, February 9, 2018, 12:15 — 1:45 p.m. and 6:00 p.m. — 7:00 p.m.
Location: Poster Board E4; Poster Abstract 357.

The study will be presented by Robert Reid, M.D. from the Virginia Cancer Specialists who served as the lead investigator of this study. The study objective was to evaluate genetic testing using the 28-gene myRisk Hereditary Cancer test in 1,162 men with a personal history of prostate cancer. Of these, 64 percent had a history of prostate cancer, while 36 percent had a history of prostate cancer and at least one additional cancer. The results showed that 12.1 percent of men with prostate cancer were positive for one or more hereditary cancer mutations in the genes tested. Additionally, the positive rate was significantly higher among men with prostate cancer plus one other cancer (14.7 percent). The inherited mutations were found in genes with a well-known prostate cancer risk (i.e., BRCA2) as well as genes historically associated with other cancer types including breast and colon. These findings suggest that hereditary cancer testing in men with prostate cancer may aid in medical management decision making to reduce overall cancer risk.

"We believe hereditary cancer testing can help inform treatment decisions for these men, including whether to pursue active surveillance, increased screening for secondary cancers and potentially for treatment selection with PARP inhibitors or other medicines in the future," said Dr. Lancaster. "Additionally, once men know they carry an inherited mutation, they can encourage their family members to get tested to learn if they’re at increased risk for cancer and potentially help them prevent future cancers."

The National Comprehensive Cancer Network, American Urological Association (AUA) and an academic consensus panel all support hereditary cancer risk assessment for patients with prostate cancer deemed to be high risk due to metastatic disease or high grade cancer with a family history of BRCA associated cancers including breast, ovarian, pancreatic or prostate cancer.

Importantly, the AUA position states that: "Patients with localized prostate cancer who are at highest risk for developing metastatic castration-resistant prostate cancer, may have a higher incidence of germline DNA repair mutations than expected from published reports. The presence of germline DNA repair gene mutations has important implications for the prostate cancer patient in terms of general cancer screening and possible future prostate cancer treatment decisions. Additionally the presence of germline DNA repair mutations is of utmost relevance to the patient’s first-degree family members due to increased cancer risk and screening implications."

About Prostate Cancer
One in nine American men will have prostate cancer during his lifetime. Prostate cancer is the second leading cause of cancer death among American men and is the most commonly diagnosed. The American Cancer Society estimates in its Cancer Facts & Figures 2018 report that 164,690 men will be told they have prostate cancer in 2018. Currently, there are nearly 2.9 million American men living with the disease and every 18 minutes another American man dies from prostate cancer. That’s a little more than 80 deaths per day and 29,430 this year.

About Myriad myRisk Hereditary Cancer
The Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 28 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma. The myRisk Hereditary Cancer test offers physicians several distinct advantages over other commercial tests, including unsurpassed lab accuracy, industry leading variant classification and exceptional customer service.

Men with prostate cancer can take the Hereditary Cancer Quiz to find out if they might be at risk for an inherited mutation and qualify for myRisk Hereditary Cancer test.

On February 7, 2018 Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company focused on the unmet needs of patients with rare diseases, reported that Will Lewis, President and Chief Executive Officer of Insmed, will present at the Leerink Partners 7th Annual Global Healthcare Conference in New York on Wednesday, February 14, 2018 at 11:30 a.m. ET (Press release, Insmed, FEB 7, 2018, View Source [SID1234523796]).

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The presentation will be webcast live and can be accessed by visiting the investor relations section of the company’s website at www.insmed.com. The webcast will be archived for a period of 90 days following the conclusion of the live event.

On February 7, 2018 Johnson & Johnson (NYSE: JNJ) reported that it will participate in the RBC Capital Markets 2018 Global Healthcare Conference on Wednesday, Feb. 21, at the Lotte New York Palace in New York City (Press release, Johnson & Johnson, FEB 7, 2018, View Source [SID1234523797]). Dominic Caruso, Executive Vice President, Chief Financial Officer will represent the Company in a session scheduled at 1:30 p.m. (Eastern Time).

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This webcast will be available to investors and other interested parties by accessing the Johnson & Johnson website at www.investor.jnj.com.

A webcast and podcast replay will be available approximately two hours after the live webcast.