AZ News from the Street 2017

Breakthrough drug status given by FDA to Tagrisso:

AGRISSO® (osimertinib) Granted Breakthrough Therapy Designation by US FDA for the 1st-Line Treatment of Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer

October 9, 2017
WILMINGTON, Del.--(BUSINESS WIRE)--

AstraZeneca today announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for TAGRISSO® (osimertinib) for the 1st-line treatment of patients with metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The Breakthrough Designation acknowledges not only TAGRISSO’s potential as a 1st-line standard of care in advanced EGFR mutation-positive NSCLC, but also the significant need for improved clinical outcomes in this disease. The results of the FLAURA trial have the potential to redefine clinical expectations and offer new hope for patients who currently have a poor prognosis.”

The FDA granted the BTD based on data from the Phase III FLAURA trial of osimertinib versus standard-of-care EGFR tyrosine kinase inhibitor (TKI) therapy in previously-untreated patients with locally-advanced or metastatic EGFR mutation-positive NSCLC. In the trial, median progression-free survival was 18.9 months for osimertinib compared with 10.2 months for EGFR-TKIs (erlotinib or gefitinib). Improvements were seen in all pre-specified subgroups, including patients with and without brain metastases.

In the FLAURA trial, the safety profile of osimertinib was consistent with previous experience. In patients treated with osimertinib, the most common AEs were diarrhea (58%, any grade [2% Grade ≥3]) and dry skin (32%, any grade [<1% Grade ≥3]), and in the comparator arm group the most common AEs were diarrhea (57%, any grade [2% Grade ≥3]) and dermatitis acneiform (48%, any grade [5% Grade ≥3]). Of the patients on osimertinib, 34% had a Grade ≥3 AE, compared to 45% in the comparator arm, and 13% of patients on osimertinib had an AE leading to treatment discontinuation compared to 18% in the comparator arm.

On September 28, 2017, the US NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) were updated to include the use of osimertinib in the 1st-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive NSCLC. The use of osimertinib for the first-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive NSCLC is not yet FDA approved.

TAGRISSO is currently approved in more than 50 countries, including the US, EU, Japan and China, as 2nd-line treatment for patients with advanced NSCLC who progress following treatment with an EGFR-TKI due to the EGFR T790M resistance mutation. TAGRISSO once-daily tablets are approved by the FDA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after an EGFR TKI therapy. TAGRISSO is the first and only approved medicine in the US indicated for NSCLC patients who have tested positive for the EGFR T790M mutation.

This is the sixth BTD that AstraZeneca has received from the FDA for an oncology medicine since 2014. BTD is designed to expedite the development and regulatory review of new medicines that are intended to treat a serious condition and that have shown encouraging early clinical results, which demonstrate substantial improvement on a clinically- significant endpoint over available medicines and when there is significant unmet medical need.

 

Oncology news:

AstraZeneca, plc AZN and partner Merck MRK announced that the FDA has granted priority review to its supplemental New Drug Application (sNDA) for Lynparza. With this sNDA, AstraZeneca and Merck are looking to expand the label of Lynparza, presently marketed for advanced ovarian cancer, to an advanced breast cancer indication." AstraZeneca, plc AZN and partner Merck MRK announced that the FDA has granted priority review to its supplemental New Drug Application (sNDA) for Lynparza. With this sNDA, AstraZeneca and Merck are looking to expand the label of Lynparza, presently marketed for advanced ovarian cancer, to an advanced breast cancer indication.

The sNDA, looking to get the drug approved for previously treated (chemotherapy) patients with HER2-negative metastatic breast cancer harboring germline BRCA1 or BRCA2 mutations, was based on data from the phase III OlympiAD study. With the FDA granting priority review, the FDA is expected to give its decision in the first quarter of 2018.

The sNDA is also the first regulatory application of this PARP inhibitor beyond ovarian cancer

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

Competition in the PARP inhibitor market has become fierce with Clovis Oncology, Inc.’s CLVS Rubraca, launched in December 2016, doing well and Tesaro, Inc. TSRO launching Zejula (niraparib), in April.

In a separate press release, AstraZeneca announced that the FDA has also granted priority review to its sNDA for key cancer drug, Imfinzi for an earlier stage of lung cancer disease. The sNDA was based on data from the phase III PACIFIC study. Interim data from the study, presented in September, showed that Imfinzi led to superior progression-free survival compared to standard of care in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) who have not progressed following chemoradiation.

Imfinzi was launched in the United States for the first indication — second line advanced bladder cancer — in May. Imfinzi is being evaluated for multiple cancers (either alone or in combination with other regimens), including phase III trials in combination with tremelimumab in first-line urothelial cancer, NSCLC, small cell lung cancer and head and neck squamous cell carcinoma (HNSCC) among others.

 

More new Oncology investments:

AstraZeneca among backers as Swiss cancer biotech raises $200 million

October 23, 2017
LONDON (Reuters) - An unlisted Swiss biotech company focused on developing "armed antibodies" to fight cancer has raised $200 million (£152 million) in a funding round backed by AstraZeneca (AZN.L) and other private backers.

The new money will allow ADC Therapeutics (ADCT) to advance two experimental drugs into clinical trials next year, which could be used to seek regulatory approval, as well as funding earlier-stage research.

ADCT specialises in developing so-called antibody drug conjugates that combine an antibody with a killer toxin to attack tumours. Roche's (ROG.S) breast cancer drug Kadcyla is a well-known example of this new type of medicine.

The latest financing means ADCT has raised a total of $455 million since its inception in 2012, when it was founded by Auven Therapeutics.

ADCT is headed by Chief Executive Chris Martin, who previously led British-based cancer specialist Spirogen, which was bought by AstraZeneca in October 2013.

The British drugmaker took a $20 million equity investment in ADCT at that time.

 

All in on Benra.

http://www.fiercepharma.com/marketing/astrazeneca-all-severe-asthma-launch-for-late-to-party-benralizumab

 

It sounds like it is going to be a very competitive product, although it is late to the party for asthma compared to GSK. It could be the best in class. Does anyone know if there are also trials going on with this drug for the COPD indication like GSK is running for their entry?

 

New oncology collaboration with Incyte announced:

Incyte's deal with AstraZeneca could widen the market for epacadostat, which is known as an IDO1 inhibitor. Incyte also has deals to test epacadostat with drugs from Dow's Merck (MRK) and Bristol-Myers Squibb (BMY), which are known as PD-1 inhibitors.

AstraZeneca and Incyte will co-fund a Phase 3 trial of epacadostat and AstraZeneca's Imfinzi, a PD-L1 inhibitor, in patients with advanced lung cancer. The trial will test the regimen vs. Imfinzi alone. Leerink's Schmidt says the trial is expected to begin enrolling in the first half of 2018.

PD-1 and PD-L1 inhibitors belong to a class of immuno-oncology drugs known as checkpoint inhibitors. Drugmakers are betting big their checkpoint inhibitors will pair well with IDO1 inhibitors, like epacadostat.

"We do see this as an additional external validation for the promise of epacadostat," RBC analyst Abrahams said. "Given (Imfinzi's) strong efficacy, the bar in this setting is high, but success could broaden the (advanced lung cancer) opportunity."

 

Why Tesaro's $2 Million Cancer-Drug Miss Prompted Its Rivals To Topple

ALLISON GATLIN
1:27 PM ET
Tesaro (TSRO) stock plunged to a 14-month low Wednesday after reporting sales of ovarian cancer drug Zejula that came in more than $2 million below analysts' expectations — prodding rivals Clovis Oncology (CLVS) and AstraZeneca (AZN) to also topple.

Off In midday trading on the stock market today, Tesaro dove 13.8%, near 906.70, after earlier plummeting in heavy volume to a low it last saw in September 2016. Meanwhile, shares of Clovis and AstraZeneca dropped 9.7% and 1%, respectively.

For the quarter, Zejula brought in $39.4 million in sales, below the consensus view for $41.6 million, Leerink analyst Seamus Fernandez wrote in a note to clients. He blamed this on higher-than-expected free drug rates and estimated compliance rates that missed assumptions.

Fernandez had assumed $45 million in Zejula sales based on expectations for 2,478 patients on the drug in September. Tesaro reported about 2,500 patients that month, but indicated the rate of free drug samples was 25%-30%, at the upper end of prior guidance for 20%-30%.

"Also, management estimates that the compliance rate may be closer to 85% (vs. our estimate of 90%)," he said. "If we apply the high end of the free-drug range (30%) and compliance of 85%, our model calculates $39.7 million in third-quarter sales, in line with the actual $39.4 million reported by Tesaro."

Tesaro also announced plans to initiate several trials of Zejula in combination with Tesaro's own immuno-oncology drug known as TSR-042 and Roche's (RHHBY) Avastin in ovarian and advanced lung cancers in the upcoming months.

 

Ooops, I did it again

AstraZeneca (AZN) Misses Q3 Earnings, Tweaks 2017 EPS View

Zacks Equity Research
November 9, 2017

AstraZeneca plc, AZN reported third-quarter 2017 core earnings of 56 cents per American Depositary Share (ADS), which missed the Zacks Consensus Estimate of 57 cents. Core earnings declined 17% year over year at constant exchange rates (CER). Lower product sales and gross margins and higher SG&A costs hurt profits in the quarter." AstraZeneca plc, AZN reported third-quarter 2017 core earnings of 56 cents per American Depositary Share (ADS), which missed the Zacks Consensus Estimate of 57 cents. Core earnings declined 17% year over year at constant exchange rates (CER). Lower product sales and gross margins and higher SG&A costs hurt profits in the quarter.

Total revenue rose 10% at CER to $6.23 billion in the reported quarter. Revenues also beat the Zacks Consensus Estimate of $5.75 billion. Revenues, however, gained mainly from the $997 million payment from Merck MRK for the oncology collaboration the companies announced in July to jointly commercialize and develop Lynparza/selumetinib.

Meanwhile, product sales declined in the quarter due to generic competition facing some legacy products.

Key growth platforms (representing 66% of total revenues) were up 6% in the quarter at CER. Among the key growth platforms, Emerging Markets, New Cardiovascular & Metabolic Diseases (CVMD), New Oncology and Japan performed well in the quarter. However, Respiratory sales declined 2% in the reported quarter.

All growth rates mentioned below are on a year-over-year basis and at CER.

Product Sales Decline

Product sales declined 2% in the quarter to $4.88 billion due to lower sales in the United States as well as Europe, which offset strong performance in emerging markets and in China.

Crestor sales declined 14% to $580 million with sales in the United States and Europe down due to the entry of multiple generic versions of the drug in the market.

Seroquel XR sales declined 68% to $62 million due to competition from generic launches.

In the quarter, Onglyza sales declined 25% to $127 million due to competitive pressure in the DPP-4 class.

Symbicort sales were down 4% in the quarter to $668 million due to lower sales in the United States and Europe. U.S. sales declined in the due to continued pricing pressure from managed-care access within the ICS/LABA class and also competition from other class like LAMA/LABA combination medicines.

Nexium recorded sales of $469 million, down 7%.

However, some legacy products that recorded growth in the quarter include Farxiga/Forxiga (up 29% to $285 million), Daliresp/Daxas (up 26% to $53 million), Faslodex (up 16% to $241 million), Iressa (up 10% to $137 million), Pulmicort (up 9% to $242 million) and Atacand (up 11% to $80 million).

Among the newer medicines, Lynparza sales rose 36% to $81 million. While sales in the United States gained from the label expansion approval in August for the treatment of second-line ovarian cancer, in Europe, sales were pushed higher by a number of successful launches.

Brilinta/Brilique sales were $284 million in the reported quarter, up 36% year over year and 4.4% sequentially. Brilinta maintained its leadership position in the U.S. branded oral anti-platelet market. In the United States., Europe and China, Brilinta continued to display an impressive performance.

Tagrisso, launched in 2015, recorded sales of $248 million, up 7% sequentially. Another new medicine, Movantik/Moventig recorded sales of $30 million in the quarter, less than $32 million in the previous quarter.

Bevespi, a LAMA/LABA in a pressurized metered dose inhaler launched commercially in the United States in January 2017, recorded sales of $4 million in the quarter, less than $3 million in the second quarter as the LAMA/LABA class grew more slowly than anticipated.

PD-L1 inhibitor Imfinzi, launched for second-line bladder cancer in the United States in May, did not generate any sales in the third quarter against $1 million in the second quarter. A regulatory application seeking label expansion of Imfinzi to treat an earlier stage of lung cancer was granted priority review by the FDA last month.

Imfinzi is a key candidate in the company’s immuno-oncology pipeline,which is beingevaluated for multiple cancers, either alone or in combination with other regimens. Last month, AstraZeneca expanded its clinical trial collaboration with Incyte INCY to evaluate Incyte’s investigational selective IDO1 enzyme inhibitor, epacadostat, in combination with Imfinzi, compared to Imfinzi alone in early lung cancer.

Regional Performance

Product sales declined 10% to $1.39 billion, primarily due to generic competition for Crestor and Seroquel XR and pricing pressure for Symbicort in the United States. European markets witnessed an 8% decline in sales to $1.19 billion. Revenues from Emerging Markets were up 10% to $1.52 billion primarily on the back of strong growth in China (up 14% to $723 million). In Established ROW market, sales were flat at $793 million

 

Brilinta, Farxiga, Faslodex and even Iressa looked surprisingly robust!

 

Asthma therapy progress:

AstraZeneca's (AZN) Asthma Drug Benralizumab Approved by FDA
Zacks Equity Research
November 15, 2017

AstraZeneca, plc AZN announced that the FDA has granted approval to its asthma disease candidate, benralizumab. Benralizumab, approved as an add-on maintenance treatment for severe eosinophilic asthma in patients aged 12 years and older, will be marketed by the trade name of Fasenra. AstraZeneca, plc AZN announced that the FDA has granted approval to its asthma disease candidate, benralizumab. Benralizumab, approved as an add-on maintenance treatment for severe eosinophilic asthma in patients aged 12 years and older, will be marketed by the trade name of Fasenra.

Shares of this London, United Kingdom based pharma giant were up more than 1% on Tuesday. So far this year, AstraZeneca’s shares have gained 21.7%, comparing favorably with the industry’s growth of 14.4%.

Fasenra will be given as a fixed-dose subcutaneous injection via a prefilled syringe, once in every eight weeks, making it the first respiratory biologic medicine to be approved with the convenient 8-week maintenance dosing schedule. GlaxoSmithKline’s GSK Nucala (subcutaneous administration) and Teva Pharmaceutical Industries' TEVA Cinqair (intravenous infusion) are presently marketed for the same indication but administered once every four weeks

The FDA approval of Fasenra was based on positive data from pivotal studies, SIROCCO and CALIMA, which showed significant reductions in exacerbations and improvements in lung function on treatment with benralizumab. Meanwhile, another phase III study, ZONDA, showed that adding benralizumab to standard of care led to statistically-significant and clinically relevant reduction in daily maintenance oral corticosteroid (OCS) use with two benralizumab dosing regimens compared with placebo.

Severe asthma patients whose disease is driven by inflammation of eosinophils, a type of white blood cell, have until now had only limited treatment options, mostly oral steroids. Fasenra, which distinctively targets and rapidly depletes eosinophils, has shown the potential to reduce oral steroid use in such patients.

Fasenra is under regulatory review in the EU, Japan and many other countries. Earlier this week, AstraZeneca said that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended marketing approval of benralizumab.

Asthma is a chronic inflammatory disease of breathlessness and has a significant unmet medical need. This is because it affects 315 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.

Benralizumab is also being evaluated for the treatment of chronic obstructive pulmonary disease (COPD) in late-stage studies. Other severe asthma candidates in AstraZeneca’s portfolio are tralokinumab and tezepelumab — in partnership with Amgen, Inc. AMGN .

 

Not much real news from AZ lately, but here is some AZ news:

AstraZeneca's COPD Drug Succeeds in Label Expansion Study

AstraZeneca AZN announced positive top-line data from a phase IV study evaluating its marketed drug, Tudorza Pressair (aclidinium bromide 400 mg, twice-daily), for an expanded indication." data-reactid="11">AstraZeneca AZN announced positive top-line data from a phase IV study evaluating its marketed drug, Tudorza Pressair (aclidinium bromide 400 mg, twice-daily), for an expanded indication.

The phase IV ASCENT was conducted to expand the label Tudorza to include patients with chronic obstructive pulmonary disease (“COPD”) with cardiovascular risk factors. The post-marketing requirement (PMR) study was requested by the FDA and was conducted on a total of 3630 patients. The study met its both primary efficacy and safety endpoints. Data from the study demonstrated that treatment with Tudorza led to a statistically significant reduction in the annual rate of moderate or severe COPD exacerbations compared with placebo.

Notably, Tudorza is a long-acting muscarinic antagonist (LAMA) which is also marketed under the brand name Eklira and Bretaris for treatment of COPD in more than 50 countries globally including the United States.A full evaluation of the ASCENT data is underway and further results will be presented at a forthcoming medical meeting. Based on positive ASCENT data AstraZeneca expects to submit a supplemental new drug application (NDA) to the FDA to expand the label of Tudorza.

The potential label expansion of Tudorza will provide the company with access to a wider patient-population base suffering from COPD.

We remind investors that in March 2015, AstraZeneca acquired the rights to Allergan's AGN branded respiratory business, which added Tudorza in its portfolio.

In April, the company entered into a strategic collaboration with Circassia Pharmaceuticals Plc for development and commercialization of Tudorza and another COPD drug Duaklir in the United States.

et al. Sales of its respiratory portfolio have declined 5% in the first nine months of the year due to pricing pressure and competition in the United States and the EU." data-reactid="35">AstraZeneca’s COPD products in the market include Symbicort, Pulmicort et al. Sales of its respiratory portfolio have declined 5% in the first nine months of the year due to pricing pressure and competition in the United States and the EU.

Importantly, the company’s promising respiratory treatments in the pipeline include tralokinumab in phase III studies for severe asthma and PT010, also in phase III studies for treating COPD. AstraZeneca expects to launch four new respiratory medicines between 2017 and 2020.

It remains to be seen if these candidates can improve the company’s respiratory sales upon approval.

Per the company’s press release, COPD is a progressive serious lung disease, commonly found to affect approximately 329 million people worldwide. Moreover, cardiovascular risks are seen to have the biggest effect on patients with COPD, representing a significant need for such therapies.