AZ News from the Street 2018

The Outlook for AstraZeneca Is Positive, But It’s Too Early to Pull the Trigger

Will Healy
InvestorPlace
September 12, 2018


AstraZeneca’s (NYSE:AZN) profits look poised to resume growing, as a number of the drug company’s new treatments are expected to be approved by regulators. However, its older blockbuster drug, Crestor, is beginning to face competition from generic treatments. While ultimately the new drugs should compensate for the lost Crestor sales, it’s too early to say when the positive outlook will be reflected in AZN stock.

But Wall Street expects the company’s profit growth to accelerate for at least the next three years. If these forecasts hold, and AZN stock can trade consistently above $40 per share, AstraZeneca stock could finally rally.

Good News And Bad News for AstraZeneca stock
Amgen (NASDAQ:AMGN), to develop the drug more quickly and expedite FDA approval of the treatment." AZN stock spiked by over 1.5% on Monday. While no significant news came out on Monday, good news and bad news for the company were reported last week. The good news was that AstraZeneca announced that the FDA had given its asthma treatment. tezepelumab, breakthrough therapy status. The designation will allow AZN and its partner on the drug, Amgen (NASDAQ:AMGN), to develop the drug more quickly and expedite FDA approval of the treatment.

Researchers believe that tezepelumab, which is injected, will treat a type of severe asthma. In Phase 2b testing, patients who took the drug suffered significantly fewer asthma attacks than those who were given placebos.

However, the company also received less favorable news regarding its treatment for a form of lupus. That drug, called anifrolumab, failed to meet a primary endpoint in late-stage testing.

New Drugs Expected to Boost AZN’s Bottom Line
Still, despite this setback, AZN’s overall pipeline appears to be robust. This year alone, positive data has been released on AstraZeneca ‘s drugs for ovarian cancer and lung cancer, while the data on another asthma treatment was also upbeat. Meanwhile, U.S. and European Union regulators approved a reformulation of Bydureon, AZN’s diabetes treatment.

Declining sales of a number of AZN’s key older drugs, particularly Crestor, have caused analysts to lower their 2018 profit estimates for AZN. They expect profits to fall by 21.8% this year. However, the future looks brighter, as analysts predicts that the company’s bottom line will rise meaningfully in 2019.

GlaxoSmithKline (NYSE:GSK), Bristol-Myers Squibb (NYSE:BMY), Pfizer (NYSE:PFE), and Merck (NYSE:MRK).The company predicts that its new drugs, along with higher emerging market sales, will boost its top line. Forecasts also indicate that it will grow more quickly than its peers such as GlaxoSmithKline (NYSE:GSK), Bristol-Myers Squibb (NYSE:BMY), Pfizer (NYSE:PFE), and Merck (NYSE:MRK).


Looking at the valuation of AZN stock, the shares’ forward price-earnings ratio stands at 22.5. That is the lowest price-earnings ratio AstraZeneca stock has reached since 2012. However, its average price-earnings ratio over the last four years was 39.4. This spread could indicate that AZN stock will head higher as the company’s new drugs compensate for Crestor’s lower sales.

Wait for AZN Stock to Break Out of Its Range
S&P 500 has increased by over 370% during the same period." However, investors should wait for AZN to have more momentum before buying the stock. Although the stock trades close to its all-time highs, it has been range-bound since 2013. Also, since the lows of 2009, the stock has risen by about 152%, while the S&P 500 has increased by over 370% during the same period.

Additionally, investors might like the stock’s 3.7% dividend yield. But the company has not increased its $1.40 per share annual dividend since 2015. Perhaps increases in the company’s profits will enable it to increase its dividend sufficiently to spark a significant rally in AZN stock. Until the shares consistently trade above $40, investors should probably watch and wait.

The Bottom Line on AZN Stock
Investors should wait for a growth catalyst before taking a position in AZN stock. With new drugs and higher emerging markets sales poised to cause AstraZeneca’s profit growth to accelerate, AZN stock should not be hurt by the sharp decline in sales of Crestor.

 

Asthma study results released:

AstraZeneca AZN announced positive long-term safety and efficacy data on Fasenra (benralizumab) from the phase III BORA extension study, evaluating the drug as an add-on maintenance treatment for severe eosinophilic asthma patients who were previously treated in pivotal SIROCCO or CALIMA studies." AstraZeneca AZN announced positive long-term safety and efficacy data on Fasenra (benralizumab) from the phase III BORA extension study, evaluating the drug as an add-on maintenance treatment for severe eosinophilic asthma patients who were previously treated in pivotal SIROCCO or CALIMA studies.

Data from the study showed that treatment with Fasenra maintained improvements in efficacy observed in the two pivotal studies over the additional 56 weeks of treatment.

The drug was approved in November last year as an add-on maintenance treatment for the indication.

Continued treatment with Fasenra stopped disease worsening (exacerbation-free) in 74% of patients who have baseline blood eosinophil count of 300 cells per μL or greater in the BORA study over the second year of treatment after being treated in previously completed SIROCCO or CALIMA studies. This number was 65% and 66% in the first year of treatment in SIROCCO and CALIMA studies, respectively. This shows that Fasenra effectively improved its efficacy over the long term. The safety and tolerability profile, and improvement in lung function and asthma control was also similar to the previous two studies.

GlaxoSmithKline’s GSK Nucala (subcutaneous administration) and Teva Pharmaceutical Industries' TEVA Cinqair (intravenous infusion) are also marketed for the same indication but administered once every four weeks. The encouraging long-term data from the BORA study coupled with the oral administration of the drug is likely to boost prospects of Fasenra going forward.

Per the press release, asthma is a chronic inflammatory disease of breathlessness and has a significant unmet medical need. This is because it affects 339 million individuals worldwide and up to 10% of patients who have severe asthma, which can become uncontrolled despite receiving high doses of standard of care medicines and require the use of chronic OCS.

However in May, Fasenra failed to meet the primary endpoint of two phase III studies — TERRANOVA and GALATHEA — to significantly reduce exacerbations compared to placebo in patients with chronic obstructive pulmonary disease.

Apart from Fasenra, the company is developing other pipeline candidates, ralokinumab and tezepelumab, for treating severe asthma in partnership with Amgen AMGN.

 

AZ only lost 1% today, the broad market lost 2%, its a relative winner!!

 

another orphan drug status granted for Lynparza. How valuable will that be?

AstraZeneca plc AZN and partner Merck & Co., Inc. MRK announced that the FDA granted Orphan Drug designation (ODD) to Lynparza for the treatment of pancreatic cancer.

Notably, the ODD is granted to drugs capable of treating rare diseases that affect less than 200,000 people in the United States.

We remind investors that in January, Lynparza became the first PARP-inhibitor to be approved for a breast cancer indication in the United States. Lynparza is also approved for advanced ovarian cancer in later settings.

Lynparza is also in different studies for a range of tumor types, including breast, prostate and pancreatic cancers as well as earlier-line settings for ovarian cancer. Lynparza also enjoys ODD status for ovarian cancer as well.

Coming back to the release, the use of Lynparza in pancreatic cancer is being evaluated in the ongoing phase III POLO study, which is testing Lynparza as maintenance monotherapy versus placebo in patients with germline BRCA-mutated metastatic pancreatic cancer whose disease has not progressed following 1st-line platinum-based chemotherapy.

Results from the POLO study are expected in the first half of 2019. Pancreatic cancer is a rare, life-threatening disease that accounts for about 3% of all cancers in the United States and has a huge unmet medical need.

In the second quarter of 2018, Lynparza sales rose 26.1% sequentially to $150 million. Sales in the United States surged 25.8% quarter-over-quarter to $83 million. In Europe, sales rose 7.1% from previous quarter, pushed by a number of successful launches, high BRCA-testing rates and increased penetration.

In 2018, Lynparza received approval in Japan for both ovarian cancer and breast cancer, and in the United States for second indication in breast cancer. These approvals should continue to drive sales further in 2018.

However, pancreatic cancer space is competitive. Another Pharma giant, Eli Lilly and Company LLY, added a pancreatic cancer candidate, pegilodecakin, to its portfolio after it acquired California-based immuno-oncology biotech, ARMO Biosciences in June 2018. Another company, Celgene Corp. CELG is working to expand the label for its drug, Abraxane for the treatment of pancreatic cancer, among others.

 

The Brexit deadlock is blocking any new AZ manufacturing investments into the UK:

PARIS (Reuters) - AstraZeneca will keep its freeze on manufacturing investments in Britain if the country's exit from the European Union fails to give enough clarity on future trading relations, the drugmaker's chairman was quoted as saying on Monday.

The comments add to pressure on British Prime Minister Theresa May to rethink her plan for leaving the EU after Brexit talks reached a stand-off at the weekend over arrangements for the UK border with Ireland.

"If a transition deal does not make clear what will happen in the future, we will maintain our decision not to invest," Leif Johansson told France's Le Monde newspaper.

"A Brexit agreement will need to ensure that Britain does not become an isolated island in the middle of the Atlantic Ocean," he added.

A spokesman for AstraZeneca said Johansson was referring to a freeze on investments in manufacturing announced in 2017.

"There has been no change to our investment plans in the UK," the spokesman said.

AstraZenca has already spent 40 million pounds ($53 million) stockpiling medicines in Britain and continental Europe to prevent supply disruptions if the two sides fail to reach a withdrawal agreement.

Some pharmaceutical companies including AstraZeneca have warned of medicine shortages in the event of a 'no deal' Brexit.

More than 2,600 drugs have some part of their manufacturing carried out in Britain. Britain exports some 45 million medical packs to EU countries each month, industry figures show, while 37 million flow to Britain from the EU.

France's largest drugmaker Sanofi said in August it would increase medicine stockpiles in Britain, echoing moves made by GlaxoSmithKline, Roche and Novartis.

"In business, uncertainty often forces you to make decisions. But what is frustrating is to have to do so when the existing system works very well," Johansson said. "This is costing us money and brings us no benefit."

($1 = 0.7602 pounds)

 

Another cancer investment by AZ:

By Ben Hirschler and Sudip Kar-Gupta

LONDON/PARIS (Reuters) - AstraZeneca is ploughing deeper into cancer immunotherapy through a wide-ranging deal with Innate Pharma, which includes the British group buying a 9.8 percent stake in the French biotech company.

Tuesday's agreement is a coup for Innate - run by former AstraZeneca executive Mondher Mahjoubi - which gains rights to sell AstraZeneca's newly approved rare blood cancer drug Lumoxiti as its first commercial product.

AstraZeneca's purchase of 6.26 million new shares in Innate at a price of 10 euros each, or double the market rate, marks a vote of confidence in the cancer immunotherapy specialist and Innate shares jumped 29 percent on the deal news.

For AstraZeneca, the tie-up is an opportunity to expand into new areas within the fiercely competitive immuno-oncology field, particularly in colorectal cancer, where the approach of boosting the immune system has so far had limited success.

AstraZeneca's move marks the latest example of premium-priced investment in biotech by big pharma, after Novartis this month announced its acquisition of cancer drugmaker Endocyte for $2.1 billion.

A key focus for AstraZeneca is Innate's experimental immunotherapy drug monalizumab, where the British company is exercising its option to obtain full oncology rights, following an earlier 2015 collaboration.

Monalizumab is currently in mid-stage clinical trials for colorectal cancer, as well as tumours of the head and neck.

"If immuno-oncology compounds can make it into colorectal cancer, it is a big opportunity - and we believe monalizumab has the potential to get us there," AstraZeneca Chief Executive Pascal Soriot told Reuters.

In addition to the 62.6 million euro ($72 million) equity stake, AstraZeneca will also make payments totalling $170 million for rights to several experimental Innate drugs, while Innate will pay up to $75 million to AstraZeneca for Lumoxiti.

Soriot is banking on new drugs, especially in cancer, to drive a sales recovery as AstraZeneca grapples with falling sales of cholesterol-fighter Crestor due to generic competition.

To date, the only immuno-oncology drug for treating colorectal cancer is Merck & Co's Keytruda and it is only cleared for around 10 percent of cases.

AstraZeneca will also gain access to Innate's anti-CD39 monoclonal antibody, IPH5201, plus four additional immuno-oncology molecules.

It will pay Innate $100 million in the first quarter of 2019 for the expansion of the collaboration on monalizumab, plus $50 million for IPH5201 and $20 million for the other four molecules.

Innate will pay AstraZeneca $50 million upfront and $25 million for future commercial and regulatory milestones for rights to Lumoxiti, which won U.S. approval last month for hairy cell leukaemia, a rare slow-growing type of blood cancer.

"This is a defining moment for us," said Innate CEO Mahjoubi. "It really means the dream has become true and the company now is a fully integrated biotech with an opportunity to commercialize a major innovative treatment."

 

Ovarian cancer positive phas 3;

MUNICH, Oct 21 (Reuters) - An AstraZeneca drug that blocks a cancer cell's ability to repair its genetic code greatly reduced the risk of ovarian cancer worsening in a phase III trial, underpinning its lead against two U.S. rivals in the same class.

Given as a maintenance therapy to reinforce initial chemotherapy, Lynparza halted or reversed tumour growth in 60 percent of patients three years into the trial. Only 28 percent of those in a chemotherapy-only control group were spared tumour progression at that stage.

At year four, the progression-free survival (PFS) rate in the Lynparza group was still above 50 percent, against 11 percent for chemotherapy alone.

"The results ... herald a new era in treatment for women diagnosed with advanced ovarian cancer who carry a BRCA mutation," said Kathleen Moore, associate professor at the University of Oklahoma's Stephenson Cancer Center, who presented the results at the European Society for Medical Oncology in Munich on Sunday.

Cancer cells with the so-called BRCA mutation have a diminished ability to restore their DNA when it gets damaged during cell division, which is a driver behind cancerous mutations.

Lynparza and other drugs in the class of so-called PARP inhibitors are designed to block what remains of that DNA repair mechanism so that BRCA-mutated cancer cells fail to replicate and the tumour can no longer sustain itself.

The drug, already approved for later use in patients with BRCA mutations and for a certain type of breast cancer, was the first PARP inhibitor to reach the market when it won U.S. approval at the end of 2014 but now faces competition from products made by Tesaro and Clovis Oncology.

British drugmaker AstraZeneca, which published some initial information on the trial in June, generated $297 million in Lynparza sales last year. Analysts on average see $2 billion in revenue from the drug in 2023, Refinitiv data shows.

The result should pave the way for expanded use of the medicine, which is being developed and marketed with Merck & Co under a deal struck last year, and AstraZeneca is in talks with regulators about approval procedures.

Getting patients on Lynparza at an early stage of treatment, so-called first-line use, puts AstraZeneca in the frame to secure longer-duration prescriptions.

Clovis Oncology's Rubraca has been approved for ovarian cancer after initial chemotherapy has failed. Tesaro, meanwhile, expects to report trial results for first-line use of its Zejula drug for ovarian cancer next year.

Pfizer's PARP inhibitor talazoparib won approval for a subtype of advanced breast cancer this week.

 

Some Nexium and Vimovo rights sold:

LONDON (Reuters) - AstraZeneca (AZN.L) said it would sell the European rights to acid-reflux medicine Nexium to Grunenthal for an upfront $700 million(546.70 million pounds) and future sales-related payments of up to $90 million as it is not in the company's targeted therapy areas.

The British company said Grunenthal, a privately owned German company, would also buy the worldwide rights, excluding the United Sates and Japan, to pain-relief drug Vimovo for $115 million plus potential additional payments of up to $17 million.

Nexium, a proton pump inhibitor developed by AstraZeneca, has lost patent protection in the majority of global markets, while Vimovo is protected in most European markets until 2025.

The rights to over-the-counter Nexium were sold to Pfizer (PFE.N) in 2012.

AstraZeneca said it would continue to manufacture and supply Nexium under a long-term supply agreement and will continue to commercialise the medicine in all markets outside Europe.

The pharmaceutical company is focussing on the three main therapy areas of oncology, cardiovascular, renal and metabolism and respiratory.

 

Is the AZ turnaround for real this time?

AstraZeneca sees years of growth as drug sales turn corner

By Ben Hirschler

LONDON (Reuters) - Strong demand for AstraZeneca's new drugs -- especially those for cancer -- drove a return to sales growth in the third quarter and the drugmaker said it anticipated years of sustained improvement and rising profit margins.

Product sales in the three months rose 8 percent, or 9 percent in constant currencies, which is the benchmark AstraZeneca uses for measuring the return to growth that it has been promising for 2018.

It is the first quarter of sustainable product sales growth since 2014 and shares in the group, which resisted a takeover bid by Pfizer in 2014, rose more than 5 percent to hit a record high of 61.85 pounds on Thursday.

AstraZeneca has faced a massive loss of patents on older drugs since 2012, wiping out more than half of its sales, but a batch of 10 new medicines -- which grew 85 percent in the latest quarter -- now offer a path to accelerating growth.

"When we set out our strategy a few years ago, not everybody believed we could transform AstraZeneca," said Chief Executive Pascal Soriot.

"Today marks an important day for the future of AstraZeneca, with the performance in the quarter and year to date showing what we expect will be the start of a period of sustained growth for years to come."

Soriot said he was "very committed" to growing operating margins as sales increased, and reiterated his confidence that annual revenue could top $40 billion by 2023.

The drugmaker first gave a bullish long-term forecast for sales of $45 billion in 2023 when it was fighting off Pfizer, since when a stronger dollar has shifted the target to nearer $40 billion in today's money.

"When we do our risk-adjusted sales forecast we still are on track to get there ... and it turns into a compound growth rate of about 12 to 13 percent a year between now and then," Soriot told analysts.


CHINA RISING

AstraZeneca's wave of new medicines include Imfinzi and Tagrisso for lung cancer, Lynparza for ovarian cancer and Fasenra for severe asthma. Sales of Tagrisso, Imfinzi and Fasenra all beat analysts' forecasts, although Lynparza missed marginally.

AstraZeneca also has high hopes for diabetes drug Farxiga, which cut heart risks in a major study. The full details of that trial will be unveiled at a medical meeting on Nov. 10.

"The continued outperformance from the new product launches and core diabetes portfolio should be well received," said Liberum analyst Graham Doyle.

China remains a stand-out market, with quarterly sales up 32 percent in the quarter, as AstraZeneca continued to outperform rivals in the world’s second biggest drugs market, where it is turning increasingly to smart tech to drive sales.

Despite the good news on the product front, however, AstraZeneca is still transitioning to its new growth phase and total revenue and earnings both fell in the quarter, as analysts had expected.

Overall revenue was down 14 percent in dollar terms to $5.34 billion and core earnings per share, which exclude some items, declined 37 percent to 71 cents, reflecting sharply lower income from divestments and investment behind new drug launches.

Analysts, on average, had forecast earnings of 72 cents on revenue of $5.30 billion, Refinitiv data showed.

For the full year, AstraZeneca reiterated its forecast of a low single-digit percentage increase in overall product sales in constant currencies and core earnings per share of $3.30 to $3.50.

 

Synagis is another old portfolio drug now being shown the door. Focus on higher margin drugs seems to be the current strategy:



LONDON, Nov 13 (Reuters) - AstraZeneca has taken another step to refocus on priority drugs by selling U.S. rights to a treatment for infant lung infections to Swedish Orphan Biovitrum for an upfront fee of $1.5 billion.

Around 130 AstraZeneca staff will transfer to Sobi as the Swedish company, widely known as Sobi, takes over marketing of the treatment Synagis in the United States.

The move is a significant commercial boost for rare diseases specialist Sobi, giving it a substantially increased U.S. footprint and expanding its business in immunology, and its shares jumped more than 6 percent.

"The addition of Synagis will become an important catalyst for Sobi's future development and will form a powerful platform for growth in rare diseases," said Chief Executive Guido Oelkers.

For AstraZeneca, whose stock gained 0.7 percent, it marks another step to streamline operations as it turns increasingly to a new batch of drugs - notably against cancer - to drive future growth.

Just last week AstraZeneca sold three older drugs for asthma and rhinitis to a small Swiss company for at least $350 million.

Sobi also gets the right to participate in AstraZeneca's share of U.S. profits and losses in a follow-on drug for respiratory syncytial virus, called MEDI8897, which AstraZeneca is developing with Sanofi, the companies said.

AstraZeneca will receive $1 billion in cash and $500 million in Sobi shares, equal to a stake of 8 percent in the Swedish group.

The British drugmaker is also entitled to further contingent payments. It will get up to $470 million in sales-related payments for Synagis, a $175 million milestone when MEDI8897 is filed for U.S. approval, and other potential payments related to the new drug of up to $170 million.

 

Diabetes news:

Farxiga phase 3 clinical study hits the primary endpoints for health outcomes

AstraZeneca also announced presentation of detailed data from a phase III cardiovascular outcomes study, DECLARE- -TIMI 58, on type II diabetes drug Farxiga at the annual session of the American Heart Association.

In September, AstraZeneca had already announced that Farxiga led to statistical significant reduction in hospitalization for heart failure (hHF) or CV death in the study, thereby meeting one of the two primary efficacy endpoints. Along with the latest release, AstraZeneca said that Farxiga significantly reduced the combined risk of hHF or CV death by 17% versus placebo. Meanwhile, for the other endpoint, though fewer major adverse cardiovascular events (MACE) were observed in the Farxiga arm, this did not reach statistical significance (8.8% for Farxiga vs. 9.4% for placebo).

The DECLARE- -TIMI 58 cardiovascular outcomes study was carried out in type-II diabetes who have multiple CV risk factors or established CV disease. The study compared the effect of Farxiga versus placebo in reducing the risk of MACE in such patients.

 

Cancer drug news:

Label expansion study for Lynparza given priority review status by FDA.

AstraZeneca plc, AZN and partner Merck’s, MRK supplemental new drug application (sNDA) looking for label expansion of their PARP inhibitor Lynparza as a first-line maintenance treatment for advanced ovarian cancer was accepted by the FDA. With the FDA granting priority review, a decision is expected in the first quarter of 2019. AstraZeneca plc, AZN and partner Merck’s, MRK supplemental new drug application (sNDA) looking for label expansion of their PARP inhibitor Lynparza as a first-line maintenance treatment for advanced ovarian cancer was accepted by the FDA. With the FDA granting priority review, a decision is expected in the first quarter of 2019.

Lynparza is already marketed in the United States for platinum-sensitive relapsed ovarian cancer regardless of BRCA status and germline BRCAm HER2-negative metastatic breast cancer.

The sNDA filing was based on data from the pivotal phase III SOLO-1 study, which demonstrated that Lynparza (olaparib) tablets led to a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) compared to placebo in women with BRCA-mutated (BRCAm) advanced ovarian cancer who were in complete or partial response following first-line standard platinum-based chemotherapy. In the Lynparza arm, 60% of the patients were progression free at 36 months compared with 27% of women in the placebo arm.

This year so far, AstraZeneca’s shares have risen 17.9% compared with the industry’s increase of 8.3%.

AstraZeneca reported Lynparza sales of $438 million in the first half of 2018, up 118% at constant exchange rates, on expanded use in ovarian cancer and label expansion in breast cancer. If approved for expanded use in the first-line setting, sales of Lynparza can improve in the future quarters.

Other PARP inhibitors available in the market are Tesaro, Inc.’s TSRO Zejula and Clovis Oncology, Inc.’s CLVS Rubraca. Zejula and Rubraca are also being evaluated in late-stage studies in the first-line maintenance setting in ovarian cancer patients who have responded to platinum chemotherapy.

 

Cancer Drug Clinical trial failure:

AstraZeneca’s AZN Imfinzi (durvalumab) monotherapy as well as in combination with tremelimumab failed to meet overall survival (“OS”) endpoint in phase III MYSTIC study evaluating it in first-line stage IV (metastatic) non-small cell lung cancer (“NSCLC”). AstraZeneca’s AZN Imfinzi (durvalumab) monotherapy as well as in combination with tremelimumab failed to meet overall survival (“OS”) endpoint in phase III MYSTIC study evaluating it in first-line stage IV (metastatic) non-small cell lung cancer (“NSCLC”).

Imfinzi, a PD-L1 inhibitor, is approved for unresectable, stage III NSCLC in second-line setting in the United States and the company is evaluating the drug in several late-stage studies for treating stage IV NSCLC. The drug is also approved for treating bladder cancer.

Shares of the company were down 1.8% on Nov 16 following the news. AstraZeneca’s shares are up 17.2% so far this year compared with the industry’s increase of 8.2%.

The MYSTIC study was evaluating Imfinzi monotherapy, and combination of Imfinzi and tremelimumab, an anti-CTLA4 antibody, compared with standard-of-care platinum-based chemotherapy in NSCLC patients who did not receive any previous treatment. The patients who were selected for analysis had their tumors expressing PD-L1 on 25% or more of their cancer cells.

Data from the study showed neither Imfinzi monotherapy nor Imfinzi combo achieved improvement in OS of statistical significance compared with chemotherapy.

In fact, data from the study last year indicated that Imfinzi as monotherapy or in combination with tremelimumab had failed to improve progression-free survival. Moreover, the OS data was expected in the first half of 2018 but a delay in the data readout was announced in March.

Imfinzi is a key drug in AstraZeneca’s immuno-oncology (“IO”) pipeline which is being evaluated for treating multiple cancers as monotherapy or in combination with other regimens including Incyte’s INCY epacadostat. Key phase III trials are valuating Imfinzi in combination with tremelimumab for hepatocellular carcinoma (HCC, liver cancer), NSCLC, small cell lung cancer and head and neck squamous cell carcinoma (“HNSCC”) among others are under way.

Successful completion of the MYSTIC study and approval for the first line indication could have helped AstraZeneca in bolstering the sales of the drug significantly as first-line lung cancer is a lucrative market. However, three other phase III studies – PEARL, NEPTUNE and POSEIDON – are evaluating the drug alone or in combination with tremelimumab in first-line NSCLC.

Meanwhile, the company’s PD-L1 inhibitor is significantly lagging the other two approved PD-L1 inhibitors – Bristol-Myers’ BMY Opdivo and Merck’s MRK Keytruda – in terms of approved indications as well as sales. While Imfinzi recorded a sales of $371 million in the first nine months of 2018, Opdivo and Keytruda generated sales of $4.9 billion and $5 billion, respectively.

Although, Imfinzi’s development did not progress well in 2018, there are several data readouts scheduled in 2019. Positive data should boost the prospects of the drug and help it achieve the potential it holds as a PD-L1 inhibitor.

 

Imfinzi is a PD-L1 inhibitor while both Keytruda and Obdivo are PD-1 inhibitor. They work on different areas of the T cell.

 

The trial design was flawed from the beginning because of cross-over! AZ learned and made design adjustments in future lung trials thus giving Durva a more successful opportunity to succeed!

 

Trial design is often the key issue for AZ.

 

Agree, that’s why they hired a few ex FDA people and changed the trial designs.

 

Cancer Data for Blood Diseases Presented:

WILMINGTON, Del.--(BUSINESS WIRE)--

27 scientific presentations, including long-term data from CALQUENCE in mantle cell lymphoma and updated early-phase trial results in chronic lymphocytic leukemia, 27 scientific presentations, including long-term data from CALQUENCE in mantle cell lymphoma and updated early-phase trial results in chronic lymphocytic leukemia

New data on six medicines and potential new medicines across a variety of blood cancers demonstrate breadth of hematology portfolio. New data on six medicines and potential new medicines across a variety of blood cancers demonstrate breadth of hematology portfolio

AstraZeneca, together with Acerta Pharma, its hematology research and development center of excellence, and MedImmune, its global biologics research and development arm, will present 27 abstracts, including six oral presentations, at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, CA, December 1-4.

New data include presentations on CALQUENCE® (acalabrutinib) and LUMOXITI™ (moxetumomab pasudotox-tdfk), as well as research findings from AstraZeneca’s early pipeline, across a variety of blood cancers.

Dave Fredrickson, Executive Vice President, Head of Oncology Business Unit, said: “In less than a year, we have launched two innovative medicines to treat blood cancers. At this year’s ASH, we will continue our momentum by presenting new results from two important trials of CALQUENCE in mantle cell lymphoma and chronic lymphocytic leukemia, and further showcase our broad pipeline with data from our novel MCL1 and CDK9 inhibitors.”

Updated results for acalabrutinib in chronic lymphocytic leukemia (CLL) Updated results for acalabrutinib in chronic lymphocytic leukemia (CLL)

Abstract #692). An oral presentation will focus on new three-year follow-up efficacy and safety results (median 33 months) from the ongoing Phase I/II ACE-CL-001 clinical trial, assessing acalabrutinib monotherapy in a cohort of treatment-naive patients with CLL (Abstract #692).

These data expand on findings previously reported and highlight the promising overall and durable response rates and safety profile in this patient population. Trial data continue to be collected and analyzed.

New long-term CALQUENCE data in previously-treated mantle cell lymphoma (MCL)New long-term CALQUENCE data in previously-treated mantle cell lymphoma (MCL)

Abstract #2876). Initial analysis of this trial served as the basis for the accelerated approval of CALQUENCE for the treatment of adult patients with MCL who have received at least one prior therapy by the US Food and Drug Administration (FDA) in October 2017. Long-term follow up data (median 26.3 months) being presented for CALQUENCE further confirm results from the registrational Phase II ACE-LY-004 clinical trial in relapsed or refractory MCL (Abstract #2876). Initial analysis of this trial served as the basis for the accelerated approval of CALQUENCE for the treatment of adult patients with MCL who have received at least one prior therapy by the US Food and Drug Administration (FDA) in October 2017.

New data from recently approved LUMOXITI New data from recently approved LUMOXITI

Abstract #1861). Results will be presented from trials of LUMOXITI in relapsed or refractory hairy cell leukemia which evaluated whether minimal residual disease eradication, as measured by different quantitative testing approaches, is associated with improved complete response duration (Abstract #1861).

Early pipeline offers new insights into MCL1 inhibition and resistance Early pipeline offers new insights into MCL1 inhibition and resistance

New data from AstraZeneca’s early hematology pipeline will be presented, including four oral presentations, on different potential new medicines across multiple blood cancers. The presentations feature new insights into the therapeutic potential of inhibiting the anti-apoptotic protein, myeloid cell leukemia-1 (MCL1) target.

Key pipeline data that will be presented includes preclinical activity of the novel MCL1 inhibitor AZD5991 in multiple myeloma (Abstract #952), findings on the potential to overcome MCL1 resistance in multiple myeloma (Abstract #472), and data on the influence of myeloma patient-derived MCL1 point mutations in MCL1-inhibitor function (Abstract #951). Data will also be presented on MCL1/CDK9 targeting by AZD5991 and the CDK9 inhibitor AZD4573 (Abstract #768)

 

AZ asthma news from Fierce Biotech:

AstraZeneca’s TLR9 oligonucleotide misses goal in asthma phase 2
by Nick Paul Taylor |
Nov 30, 2018 9:12am


A phase 2a trial of AstraZeneca’s AZD1419 has missed its primary endpoint. AstraZeneca moved the Dynavax-partnered TLR9 agonist into the trial in the belief it could improve time to loss of asthma control in patients with eosinophilic, moderate-to-severe forms of the disease.

Dynavax designed AZD1419, an inhaled synthetic oligonucleotide containing immunostimulatory CpG motifs, to be a potent and specific agonist for TLR9. The idea was to trigger prolonged reductions in asthma symptoms by altering how the immune system responds to allergens. If AZD1419 achieved that goal, it may have freed patients from the need to take inhaled corticosteroids, muscarinic antagonists and beta agonists as maintenance therapies.

However, if the phase 2a is any guide, AZD1419 will fall short of that goal. AstraZeneca is yet to make a statement about the trial, but Dynavax revealed it missed the primary endpoint of time to loss of asthma control.

According to Dynavax, the 13-week trial suggested the drug is safe, well tolerated and activates the TLR9 pathway. The positives are more than offset by the primary endpoint miss, though. AstraZeneca is now going through the data before making a decision on the future of the program.

AstraZeneca began working with Dynavax in 2006 and amended the agreement five years later to get AZD1419 into the clinic. Back then, AstraZeneca paid $3 million to get the clinical program started and committed to handing over $20 million to cover the cost of Dynavax taking the drug through to phase 2a.

In 2014, the partners decided to skip phase 1b and jump straight into phase 2b on the strength of data from 45 healthy volunteers. Progress slowed after that, though. Dynavax had expected to move into phase 2a in the first half of 2015. In January 2016, with the trial yet to start, AstraZeneca took responsibility for running the phase 2a.

AstraZeneca’s action got the program moving forward again. Enrollment in the trial began around the start of 2017, and the study wrapped up on schedule two months ago.

 

GSK buys Tesaro maker of Zejula, one of the AZ PARP drug Lynparza's rivals:

GSK buys U.S. cancer drugmaker Tesaro for hefty $5.1 billion
By Ben Hirschler,
Reuters
December 3, 2018

By Ben Hirschler

LONDON (Reuters) - GlaxoSmithKline <GSK.L> has agreed to buy U.S. cancer specialist Tesaro <TSRO.O> for $5.1 billion, marking a major biotech investment by Chief Executive Emma Walmsley as she seeks to rebuild the group's pharmaceuticals business.

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 now wants to change.

Britain's biggest drugmaker is paying $75 a share for the business, an 110 percent premium to the 30-day average price. It is also taking on Tesaro's debt. News of the lofty valuation sent GSK shares down 7 percent on Monday.

Boston-based Tesaro has long been seen as a potential takeover target, with other suggested acquirers in the past including Switzerland's Roche <ROG.S>.

The definitive agreement to acquire Tesaro comes on the same day as GSK sold its India-focused Horlicks nutrition business to Unilever <ULVR.L> for $3.8 billion, freeing up cash for pharmaceuticals investment.

Tesaro gives GSK a marketed product for ovarian cancer, Zejula, which belongs to the promising new class of medicines called poly ADP ribose polymerase (PARP) inhibitors. GSK's UK rival, AstraZeneca <AZN.L>, sells the rival PARP drug Lynparza, while Clovis Oncology <CLVS.O> markets another 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 tumors 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 was advised by Citi and Centerview Partners, while PJT Partners and BoA Merrill Lynch worked for GSK.