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Monday, December 3, 2018

Alexion: Positive Phase 3 Data for Hemoglobinuria Med at ASH


– First Conference Presentation of Results for ALXN1210 in Patients on Soliris® (Eculizumab) at ASH –
– Publications in Blood of Results for ALXN1210 in Complement Inhibitor-Naïve Patients and Patients on Soliris® –
– Presentation at ASH of New Results from Sensitivity Analyses in Inhibitor-Naïve Patients, and Analyses of C5 Inhibition and Breakthrough Hemolysis in Inhibitor-Naïve Patients and Patients on Soliris® –
Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced the presentation of comprehensive positive Phase 3 data for ALXN1210, the company’s investigational long-acting C5 complement inhibitor, at the American Society of Hematology (ASH) Annual Meeting, taking place December 1-4, 2018. The presentations included both previously announced and new data from the two large Phase 3 studies in patients with paroxysmal nocturnal hemoglobinuria (PNH) who had either never been treated with a complement inhibitor before or who had been stable on Soliris® treatment. The conference presentations coincided with publications in Blood of the positive results on all primary and key secondary endpoints from these two studies.
“We are excited by the increasing body of data from our two active comparator-controlled Phase 3 studies, the largest PNH Phase 3 program ever conducted, on clinically meaningful endpoints in this devastating and potentially life-threatening disease. We are particularly pleased by the positive data in patients converting to ALXN1210 from Soliris®,” said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. “Our ambition is to make ALXN1210 the new standard of care for patients with PNH.”

BioLife: Kolon TissueGene Doses 1st Patient in Phase 3 Osteoarthritis Trial


On November 21, 2018, BioLife’s customer Kolon TissueGene, Inc., a leader in advanced cell and gene therapies, announced that it has dosed its first patient in its pivotal US Phase III clinical trials for Invossa, a cell and gene therapy in development for knee osteoarthritis (OA).
‘This is an exciting step for Kolon TissueGene as we progress towards providing key clinical benefits for patients of this debilitating disease with this novel cell and gene therapy for knee osteoarthritis,’ stated Mr. Woosok Lee, President and CEO of Kolon TissueGene.
Kolon TissueGene is conducting pivotal Phase III trials for US approval of Invossa for knee osteoarthritis. The pivotal phase III trials for US approval of Invossa will enroll close to 1,020 patients in approximately 60 clinical sites across the United States. The trial investigators include orthopedic surgeons, rheumatologists and pain specialists. During the trial, the company will assess pain and function endpoints as well as MRI, X-Ray and liquid biomarkers.
In addition to demonstrating significant improvements in pain relief and function, the trials are designed to show structural benefits, including a delay in disease progression, and if successful could achieve a Disease Modifying Osteoarthritis Drug or ‘DMOAD’ label claim. Such an indication by the FDA would be a first for any osteoarthritis drug approved in the US.

Momenta Updates on Strategy for Proposed Biosimilar to HUMIRA


Momenta Pharmaceuticals, Inc. (Nasdaq: MNTA), a biotechnology company with a validated scientific platform focused on discovering and developing novel therapeutics to treat rare, immune-mediated diseases, today announced a revised regulatory strategy in the United States for M923, Momenta’s proposed biosimilar to HUMIRA. Momenta had previously guided that it planned to file a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in the fourth quarter of this year.
With the recent Abbvie agreement, Momenta will be able to commercialize M923 in the United States, pending regulatory approval, as early as November 20, 2023. Momenta has decided to delay the filing of the BLA, which may reduce program costs in 2019 without delaying potential US market entry for M923.
“The clarity on the US entry date provided by our settlement with Abbvie allows us to better align our regulatory and manufacturing strategies and enables us to defer expenses without impact to our launch timing,” said Craig Wheeler, President and Chief Executive Officer of Momenta.

GSK slides after buying cancer firm Tesaro for hefty $5.1 billion

 GlaxoSmithKline has agreed to buy U.S. cancer specialist Tesaro for $5.1 billion (4 billion pounds), a costly investment to rebuild the pharmaceuticals business by new Chief Executive Emma Walmsley that unnerved investors.

GSK has lagged rivals in recent years in producing multibillion-dollar blockbusters and it largely sat out a spate of dealmaking by rival drugmakers under previous CEO Andrew Witty. That is a situation Walmsley wants to change.
Britain’s biggest drugmaker is paying $75 a share for Tesaro, an 110 percent premium to the 30-day average price. It is also taking on Tesaro’s debt.
News of the lofty valuation and the fact that buying Tesaro will take years to pay off sent GSK shares down 8 percent on Monday, their biggest daily fall in 10 years.
Boston-based Tesaro has long been seen as a potential takeover target, with other suggested acquirers in the past including Switzerland’s Roche.
The definitive agreement to acquire Tesaro, which means GSK has to pay $162.5 million if the tie-up is terminated, comes on the same day as GSK sold its India-focused Horlicks nutrition business to Unilever for $3.8 billion, freeing up cash.
Tesaro gives GSK a marketed product for ovarian cancer, Zejula, which belongs to a promising class of medicines called poly ADP ribose polymerase (PARP) inhibitors.
But Zejula lags behind AstraZeneca and Merck & Co’s rival PARP drug Lynparza, which sells nearly three times more, while Clovis Oncology also has a competitor called Rubraca.
PARP inhibitors work by blocking enzymes involved in repairing damaged DNA, thereby helping to kill cancer cells, and they are a growing focus for drug research, with potential for use beyond ovarian tumours in breast, lung and prostate cancers.
For GSK, making Zejula work in wider population groups will be critical in justifying the high price it is paying.
Walmsley, who took over in April 2017, has made replenishing GSK’s medicines cabinet her top priority. She recently hired a business development executive from Roche’s Genentech, another signal of her readiness to make acquisitions.
“This is an example of us executing on what we said we were going to do … to bring growth, pipeline, commercial capability and near-term catalysts,” she told reporters.
“We still will be open to other potential bolt-ons in business development,” Walmsley added.
IMMUNOTHERAPY PIPELINE
GSK said buying Tesaro would weigh on adjusted earnings for the first two years by mid to high single digit percentage rates, but the acquisition should be accretive by 2022. The deal is expected to complete in the first quarter of 2019.
The company’s dividend policy will not be affected by the deal and GSK still expects to pay 80 pence a share in 2018.
Zejula’s revenues in its current approved indication as second-line maintenance treatment for ovarian cancer were $166 million in the nine months to September.
Industry analysts, on average, expect annual Zejula sales to reach $1 billion by 2023, according to Refinitiv data.
In addition to Zejula, Tesaro also has several oncology medicines in development, including a number of experimental immunotherapy treatments.
That dovetails with GSK’s other work in cancer, a field where it has had a patchy track record in the past.
Three years ago, GSK sold its established cancer medicines to Novartis. But it retained some early-stage projects that it now believes have the potential to leapfrog rivals and be at the forefront of treatment.
They include an antibody drug for multiple myeloma, which could be launched in 2020, as well as new kinds of cell therapies designed to modify patients’ immune cells.
Tesaro shares, which have run up in recent weeks on takeover speculation, jumped 60 percent to nearly $74 in early trade on Nasdaq, while Clovis also gained 15 percent.
Tesaro was advised by Citi and Centerview Partners, while PJT Partners and BoA Merrill Lynch worked for GSK.

Long-Term Care Insurance Policies Weigh Down GE and Other Companies


General Electric Co.’s bet on selling long-term care insurance policies, which ballooned into a $16.5 billion liability, underscores how policies meant to pay for nursing homes and prescription costs have become one of the most unpredictable segments of the insurance industry.
GE’s skyrocketing liability is but only one example of an industrywide lapse in judgment when assessing the future cost of such care, industry experts said. Prudential Financial Inc., which stopped issuing long-term care insurance in 2012, recorded a $1.5 billion charge related to its portfolio in the second quarter. Genworth Financial Inc., which is among the roughly dozen companies still offering this type of insurance, has incurred more than $3 billion in losses stemming from these plans.
GE in January reported a $6.2 billion charge linked to liabilities for long-term care insurance policies, which prompted federal regulators to expand a probe into the company’s accounting practices. The company has said it is cooperating with investigators.
The Wall Street Journal reported Friday that former GE employees told federal investigators that the company failed to acknowledge worsening results in the insurance business.
GE also faces shareholder lawsuits alleging that it understated risks related to its insurance operations.
“We are exploring every option to manage and mitigate risk from the company’s legacy insurance liabilities,” said a GE spokeswoman, who declined to comment on specifics of ongoing legal matters. “We have a strong commitment to integrity in our controllership and financial reporting.”
Insurers make the bulk of their money from the premiums charged to policyholders and from investing those premiums before paying out claims. Forecasting the future payout for long-term-care policies can prove particularly difficult.
That calculation involves census data, actuarial science and mortality rates, among other mercurial variables. But it also requires guesswork around the future price of health care.
“Assisted living, health care and prescriptions — the inflation rate in those things is massive,” said Peter Bible, a partner and chief risk officer at accounting firm EisnerAmper LLP.
Muddying the math is the unpredictable nature of regulation, which could affect the portion of costs shouldered by the government. “It’s very complicated science,” said Mr. Bible, a former chief accounting officer at General Motors Co.
In recent decades, many long-term care plan providers underestimated the payouts they would face when plans came due and didn’t charge high enough premiums. Companies also misjudged how long claims would be paid out as consumers lived longer.
Moreover, the low interest-rate environment during the past decade has dented the investment returns of insurance companies.
“Who could have predicted interest rates would have been this low for this long,” said Jesse Slome, executive director of the American Association for Long-Term-Care Insurance.
The dozen companies that offer a long-term care product include Northwestern Mutual, Mutual of Omaha and Transamerica Corp., according to Mr. Slome, down from about 75 in the 1980s, when long-term-care insurance became popular.
Insurance companies have recorded more than $28 billion in charges related to long-term care insurance policies since 2007, according to estimates by analysts at investment bank Evercore ISI.
Changes in GE’s risk assessment and assumptions triggered a $6.2 billion charge related to the insurance portfolio, the company explained in a January conference call. At the time, GE estimated it will need to contribute roughly $15 billion to its insurance business over the next seven years.
GE stopped selling long-term care policies in 2006, but the company hadn’t reassessed the assumptions behind the likely risks of these plans until 2017, said Ryan Zanin, GE Capital’s chief risk officer at the time, during the call.
GE Capital is the company’s financial services unit. Mr. Zanin left GE in June to pursue opportunities outside the company, a GE spokeswoman said.
GE performed an annual test to ensure future premiums and reserves would cover future claims, as required by regulators. Because the company cleared the hurdle in previous years, it had to leave in place existing risk assumptions, Mr. Zanin said on the call.
That changed in 2017, however, when a surge in claims by one segment of GE’s insurance portfolio triggered a review. The policyholders in that block were approaching 80 years or older, when the bulk of claims tend to arise, Mr. Zanin said.
“Virtually, the entire industry has experienced greater claims than originally anticipated where more people go on claim and for longer than expected,” he said on the call.
Prudential’s charge, reported in August, followed a similar annual review of the profitability of its remaining long-term care portfolio. A Prudential spokesman declined to comment.
Genworth Financial, which was spun off from GE in 2006, has incurred a cumulative statutory net loss of over $3 billion as of Sept. 30, stemming from its legacy long-term care insurance business.
Genworth continues to lose hundreds of millions on these legacy blocks each year, a company spokeswoman said.
The company evaluates its assumptions annually and has taken a proactive approach to premium increases, achieving approximately $10 billion in approved rate increases on some of its older products, the spokeswoman said. The company is also working with regulators to adopt a system of re-rating long-term care premiums annually, in a way that is similar to how insurers adjust premiums on homeowners, auto and health insurance, the spokeswoman said.
GE is seeking ways to mitigate its exposure to long-term care insurance, the company’s executives have since said.
GE was expected to perform in the fourth quarter the annual reserves-adequacy test, the inputs for which were reset last year. In advance of that, GE management anticipated an additional capital infusion of $3 billion into the insurance business in 2019, GE finance chief Jamie Miller said on an earnings call in October.

GSK Makes $5.1 Billion Bet on Tesaro Oncology and Its PARP Inhibitor Zejula


Shares of Tesaro Oncology shot up more than 60 percent in premarket trading after pharma giant GlaxoSmithKline announced it will acquire the Waltham, Mass.-based company for $5.1 billion. For GSK, the deal marks an increased focus on oncology as it focuses on high growth areas.
For GSK, the deal will bolster its pharmaceutical business and accelerate the build of its pipeline and commercial operations in the oncology space. GSK has been streamlining its operations to focus on drug development that will accelerate growth, such as in oncology. Acquiring Tesaro reverses a move that GSK made several years ago when it divested itself of a significant number of oncology products in a $20 billion deal with Novartis. GSK swapped out some oncology assets for Novartis’ vaccine business and a joint share of an over-the-counter consumer healthcare business – a business that GSK acquired in total earlier this year for $13 billion.

From the deal with Tesaro, GSK gains Tesaro’s Zejula, an oral, once-daily PARP inhibitor used as maintenance treatment for ovarian cancer that secured approval from the U.S. Food and Drug Administration (FDA) in 2017. Zejula was the first PARP inhibitor to be approved by the FDA that does not require BRCA mutation or other biomarker testing. In the first three quarters of this year, Zejula has brought in revenue of $166 million in its current approved indication as second-line maintenance treatment for ovarian cancer.
Ovarian cancer is the fifth leading cause of cancer-related deaths in the United States. It is estimated that this year there will be more than 22,000 women in the U.S. diagnosed with the disease and about 14,000 disease-related deaths.
Zejula is currently being investigated as a monotherapy and first-line treatment for ovarian cancer patients across all patient populations. The clinical trials are investigating the benefit of Zejula in patients who carry BRCA mutations as well as the larger population of patients without BRCA mutations whose tumors are HRD-positive and HRD-negative. The first study results are anticipated in the second half of 2019.
Hal Barron, head of R&D at GlaxoSmithKline, said the company has a strong belief that PARP inhibitors are “important medicines that have been underappreciated in terms of the impact they can have on cancer patients.” He said the company is optimistic that Zejula will demonstrate a benefit in ovarian cancer patients beyond the BRCA mutation. He also stressed that the company is excited about Zejula’s other potential uses in targeting additional tumor types. Earlier this summer, Barron unveiled a long-term plan for R&D at GSK that is focused on the immune system and genetics.
In its announcement this morning, GSK said it believes PARP inhibitors such as Zejula can provide “significant opportunities” in the treatment of other types of cancer. Zejula is being studied for potential use in the treatment of lung, breast and prostate cancer, both as a monotherapy and in combination with other medicines, such as Tesaro’s own checkpoint inhibitor, dostarlimab, formerly known as TSR-042. Tesaro has plans to file a BLA next year for TSR-042. Tesaro has several anti-PD1 antibodies in its developmental pipeline, as well as inhibitors of TIM-3 and LAG-3.
GSK Chief Executive Officer Emma Walmsley said the deal for Tesaro will not only strengthen the company’s pipeline, but will also increase GSK’s commercial footprint and provide the company with additional access to “new scientific capabilities.”
“This combination will support our aim to deliver long-term sustainable growth and is consistent with our capital allocation priorities. We look forward to working with Tesaro’s talented team to bring valuable new medicines to patients,” Walmsley said in a statement.
GSK will acquire Tesaro for a price of $75 per share in an all-cash deal. The transaction is expected to close in the first quarter of 2019. Shares of Tesaro closed at $46.38 on Friday, but in early trading today have soared to $74. GSK said it is in discussion with several Tesaro executives to ensure their continued employment with the company when the transaction is complete.

Geron announces new survival data from IMbark study of Imetelsat in MF patients


Geron announced that results from IMbark, a Phase 2 clinical trial of imetelstat treatment in Intermediate-2 or High-risk myelofibrosis, or MF, patients who are relapsed or refractory to a Janus Kinase inhibitor, were presented at the 60th American Society of Hematology Annual Meeting in San Diego, California. Geron CEO John A. Scarlett said: “The IMbark results suggest a meaningful survival outcome in this poor-prognosis, relapsed/refractory MF patient population where there are currently no approved treatmentWe plan to explore potential late-stage development opportunities for imetelstat in MF through discussions with experts in MF and regulatory authorities and expect to provide a decision regarding future development of imetelstat in this patient population by the end of the third quarter of 2019.” IMbark is a Phase 2 clinical trial that evaluated two starting dose levels of imetelstat in more than 100 patients with Intermediate-2 or High-risk MF who have relapsed after or are refractory to prior treatment with a JAK inhibitor. The oral presentation highlighted efficacy and safety data from the primary analysis, as well as overall survival data with a clinical cutoff of October 22, 2018 and a median follow up of approximately 27 months. The new data presented at ASH indicate that median overall survival for the 9.4 mg/kg dosing arm was 29.9 months, which suggests a meaningful survival outcome with imetelstat treatment in this poor-prognosis patient population, all of whom met rigorous criteria for having failed or not responded to JAK inhibitor treatment prior to enrollment in the trial. Other observational studies of similar patient populations published in medical literature have reported median OS ranged from approximately 12-14 months. The safety profile reported for imetelstat-treated patients in IMbark was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified. Cytopenias, particularly neutropenia and thrombocytopenia, were the most frequently reported adverse events which were predictable, manageable and reversible.
https://thefly.com/landingPageNews.php?id=2831559