On April 25, 2017 AstraZeneca reported that the European Commission (EC) has granted full marketing authorisation for Tagrisso (osimertinib) 40mg and 80mg once-daily tablets for the treatment of adult patients with locally-advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, APR 25, 2017, View Source [SID1234518677]).

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The full approval for Tagrisso is based on the results of the Phase III AURA3 trial, which were presented last year. The EGFR T790M mutation can be detected with a validated test using either DNA derived from a biopsy or circulating tumour DNA (ctDNA) obtained from a plasma sample.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "The full approval of Tagrisso in the EU is further evidence of our exciting progress in transforming the science of cancer care to deliver life-changing medicines to people most in need. Having demonstrated its superiority over chemotherapy in EGFR T790M mutation-positive non-small cell lung cancer, Tagrisso has the potential to become the new standard of care for patients with this difficult-to-treat form of lung cancer."

Data from the Phase III AURA3 trial showed that Tagrisso demonstrated statistically-significant improvements in progression-free survival (PFS) over standard platinum-based doublet chemotherapy in 419 patients with EGFR T790M-positive advanced NSCLC whose disease had progressed on or after EGFR TKI therapy. Among patients taking Tagrisso, the PFS was 10.1 months, compared to 4.4 months in the chemotherapy arm. The objective response rate (ORR) was 71% compared to 31% for chemotherapy. Among 144 patients with metastases to the central nervous system (CNS), PFS was 8.5 months versus 4.2 months.

The most common adverse reactions in the Tagrisso group were diarrhoea (41% overall; 1% Grade ≥3), rash (34% overall; 1% Grade ≥3), dry skin (23% overall; 0% Grade ≥3), paronychia (22% overall; 0% Grade ≥3), stomatitis (15% overall; 0% Grade ≥3, and pruritus (13% overall; 0% Grade ≥3). Warnings and precautions include interstitial lung disease (ILD), keratitis, left ventricular ejection fraction (LVEF) and QTc interval prolongation.

In March 2017, the US Food and Drug Administration (FDA) granted Tagrisso a conversion from accelerated to full approval. Tagrisso was also recently approved in China through the new Priority Review Pathway, which grants an accelerated review timeline for innovative therapies.

About Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths, more than breast, prostate and colorectal cancers combined. Patients who have EGFRm NSCLC, which occurs in 10-15% of NSCLC patients in the US and Europe and 30-40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to treatment, leading to disease progression. Approximately two-thirds of patients develop resistance to approved EGFR-TKIs such as gefitinib, erlotinib and afatinib due to the secondary mutation, T790M.

About Tagrisso

Tagrisso (osimertinib) 40mg and 80mg once-daily oral tablet has been approved in over 45 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC. Eligibility for treatment with Tagrisso is dependent on confirmation that the EGFR T790M mutation is present in the tumour.

Tagrisso is a third generation, irreversible EGFR-TKI designed to inhibit both EGFR sensitising and EGFR T790M resistance mutations and to have activity in the CNS. Tagrisso is also being investigated in the adjuvant and metastatic 1st line settings, including in patients with and without CNS metastases, in leptomeningeal metastases, and in combination with other treatments.

About AstraZeneca in Lung Cancer

AstraZeneca uses ground-breaking science to develop a wide range of therapies for patients with lung cancer. We are pioneering biomarker-guided therapies that aim to eliminate lung cancer by targeting molecular mutations in tumour cells and by boosting the power of the immune response against cancer. We are committed to transforming outcomes for patients with lung cancer, whose treatment options are currently limited.

On April 25, 2017 Eli Lilly and Company (NYSE: LLY) reported financial results for the first quarter of 2017 (Press release, Eli Lilly, APR 25, 2017, View Source [SID1234518686]).

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$ in millions, except per share data
First Quarter
%

2017

2016
Change
Revenue
$
5,228.3


$
4,865.1

7
%
Net Income (Loss) – Reported
(110.8)


440.1

NM
Earnings (Loss) Per Share – Reported
(0.10)


0.41

NM





Net Income – Non-GAAP
1,039.6


882.3

18
%
EPS – Non-GAAP
0.98


0.83

18
%


Certain financial information for 2017 and 2016 is presented on both a reported and a non-GAAP basis. Some numbers in this press release may not add due to rounding. Reported results were prepared in accordance with generally accepted accounting principles (GAAP) and include all revenue and expenses recognized during the periods. Non-GAAP measures exclude the items described in the reconciliation tables later in the release. The company’s 2017 financial guidance is also being provided on both a reported and a non-GAAP basis. The non-GAAP measures are presented to provide additional insights into the underlying trends in the company’s business.

"Lilly’s new product launches, including Trulicity and Taltz, led the company to a strong quarter of volume-driven revenue growth. We achieved this growth while maintaining our commitment to expand margins and improve productivity," said David A. Ricks, Lilly’s president and CEO. "The progress we made in the first quarter continues the positive momentum we’ve built over the past few years. We remain on track to sustain a steady flow of innovation that has the potential to improve patients’ lives and create value for shareholders."

Key Events Over the Last Three Months

Commercial

The company and Boehringer Ingelheim launched Synjardy XR (empagliflozin and metformin hydrochloride extended-release) tablets in the U.S. for adults with type 2 diabetes. Synjardy is part of the company’s alliance with Boehringer Ingelheim.
Regulatory

With respect to Olumiant (baricitinib) on which we collaborate with Incyte:
The European Commission granted marketing authorization for 4 mg and 2 mg film-coated tablets in the European Union for the treatment of moderate-to-severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to, one or more disease-modifying antirheumatic drugs. Olumiant has been launched in select European countries.
The U.S. Food and Drug Administration (FDA) issued a complete response letter for the New Drug Application (NDA) of baricitinib, an investigational medication for the treatment of moderate-to-severe rheumatoid arthritis, indicating that the FDA is unable to approve the application in its current form. The FDA specifically stated that additional clinical data are needed to determine the most appropriate doses and to further characterize safety concerns across treatment arms.
The European Commission approved an update to the Synjardy label to include a change to the indication statement and inclusion of data on the reduction of risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease when treated with empagliflozin.
The FDA approved updates to the label for Trulicity (dulaglutide) to include use in combination with basal insulin for adults with type 2 diabetes.
Clinical

With respect to Phase 3 trials of abemaciclib, a cyclin-dependent kinase (CDK)4 and CDK6 inhibitor, being tested in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer:
The company announced that abemaciclib, in combination with fulvestrant, in women who have relapsed or progressed after endocrine therapy was superior to fulvestrant plus placebo on progression-free survival. Lilly intends to initiate global submissions of these results, as well as for single-agent abemaciclib based on a previous Phase 2 study, beginning in the second quarter of 2017.
The company announced results of a preplanned interim analysis, evaluating abemaciclib, in combination with an aromatase inhibitor (letrozole or anastrozole), compared to treatment with an aromatase inhibitor plus placebo. The trial met its primary endpoint of demonstrating statistically significant improvement in progression-free survival. In addition, improvement was shown in a key secondary endpoint of objective response rate. Lilly intends to begin global submissions of these results in the third quarter of 2017.
The company announced that patients with moderate-to-severe plaque psoriasis treated with Taltz (ixekizumab) demonstrated superior efficacy at 24 weeks compared to patients treated with Stelara (ustekinumab).
Business Development/Other

The company completed its acquisition of CoLucid Pharmaceuticals. As a result of this acquisition, lasmiditan, in development for the acute treatment of migraine, has been added to Lilly’s Phase 3 pipeline.
The Japan IP High Court confirmed the decisions of the Japan Patent Office and ruled in Lilly’s favor in the invalidation trials initiated by Sawai regarding Lilly’s vitamin regimen patents for Alimta (pemetrexed disodium).
The company announced plans to invest $850 million in its U.S. operations in 2017. The company’s investments span facilities across its U.S. enterprise, including research laboratories, manufacturing sites, and general and administrative areas. The investments are being driven by demand for Lilly products, as well as the company’s robust pipeline of potential medicines in development targeting cancer, pain, diabetes and other unmet medical needs.
First-Quarter Reported Results

In the first quarter of 2017, worldwide revenue was $5.228 billion, an increase of 7 percent compared with the first quarter of 2016. The revenue increase was driven by an 8 percent increase due to volume, partially offset by a 1 percent decrease due to the unfavorable impact of foreign exchange rates. The increase in worldwide volume was largely due to 9 percent pharmaceutical growth driven by Trulicity, Taltz and other new products including Cyramza, LartruvoTM, Basaglar and Jardiance. To a lesser extent, the increase in volume was also driven by companion animal products due to the inclusion of $40.8 million in revenue from the acquisition of Boehringer Ingelheim Vetmedica’s U.S. feline, canine and rabies vaccine portfolio. These total volume increases were partially offset by decreased volumes for Zyprexa and Alimta.

Revenue in the U.S. increased 15 percent, to $2.934 billion, driven primarily by increased volumes for Trulicity, Taltz, Lartruvo and companion animal products due to the inclusion of revenue from the acquisition of Boehringer Ingelheim Vetmedica’s U.S. feline, canine and rabies vaccine portfolio, partially offset by decreased volume for Alimta. Realized prices increased U.S. revenue by 3 percent, primarily driven by Humalog, which had significant unfavorable changes to rebates and discounts in the first quarter of 2016 that did not recur in the first quarter of 2017.

Revenue outside the U.S. decreased 1 percent, to $2.295 billion, due to lower realized prices and volume from the loss of exclusivity for several products including Cymbalta in Canada and Europe, Zyprexa in Japan and Alimta in numerous countries, as well as the unfavorable impact of foreign exchange rates. These were largely offset by increased volume for several newly launched pharmaceutical products, including Trulicity and Cyramza.

Gross margin increased 10 percent, to $3.901 billion, in the first quarter of 2017 compared with the first quarter of 2016. Gross margin as a percent of revenue was 74.6 percent, an increase of 1.8 percentage points compared with the first quarter of 2016. The increase in gross margin percent was primarily due to manufacturing efficiencies.

Operating expenses in the first quarter of 2017, defined as the sum of research and development, and marketing, selling and administrative expenses, were $2.783 billion, an increase of 3 percent compared with the first quarter of 2016. Research and development expenses increased 1 percent, to $1.238 billion, or 23.7 percent of revenue. Marketing, selling and administrative expenses increased 5 percent, to $1.545 billion, due to increased expenses related to new pharmaceutical products, partially offset by decreased expenses related to late life-cycle products. Operating expenses were 53.2 percent of revenue in the first quarter of 2017, a reduction of 2.2 percentage points compared with the first quarter of 2016.

In the first quarter of 2017, the company recognized an acquired in-process research and development charge of $857.6 million associated with the acquisition of CoLucid Pharmaceuticals. There were no acquired in-process research and development charges in the first quarter of 2016.

In the first quarter of 2017, the company recognized asset impairment, restructuring and other special charges of $213.9 million, primarily related to severance costs incurred as a result of actions taken to reduce the company’s cost structure, as well as integration costs related to the acquisition of Novartis Animal Health. In the first quarter of 2016, the company recognized asset impairment, restructuring and other special charges of $131.4 million, composed of asset impairments related to the closure of an animal health manufacturing facility in Ireland and integration costs related to the acquisition of Novartis Animal Health.

Operating income in the first quarter of 2017 was $46.1 million, a decrease of $669.7 million compared with the first quarter of 2016, primarily driven by an acquired in-process research and development charge for the acquisition of CoLucid Pharmaceuticals, partially offset by revenue growth.

Other income (expense) was income of $15.1 million in the first quarter of 2017, compared with expense of $149.0 million in the first quarter of 2016. Other expense in the first quarter of 2016 was driven by a $203.9 million charge related to the impact of the Venezuelan financial crisis.

During the first quarter of 2017, the company incurred $172.0 million of income tax expense, despite earning $61.2 million of income before income taxes, as a result of the nondeductible $857.6 million acquired in-process research and development charge for the acquisition of CoLucid Pharmaceuticals. During the first quarter of 2016, the company’s effective tax rate was 22.4 percent.

In the first quarter of 2017, net income (loss) and earnings (loss) per share were $(110.8) million and $(0.10), respectively, compared with $440.1 million and $0.41, respectively, in the first quarter of 2016. These decreases in net income (loss) and earnings (loss) per share were primarily driven by lower operating income, partially offset by higher other income.

First-Quarter Non-GAAP Measures

On a non-GAAP basis, first quarter 2017 gross margin increased 10 percent, to $4.085 billion. Gross margin as a percent of revenue was 78.1 percent, an increase of 1.8 percentage points compared with the first quarter of 2016. The increase in gross margin percent was primarily due to manufacturing efficiencies.

Operating expenses were 53.2 percent of revenue in the first quarter of 2017, a reduction of 2.2 percentage points compared with the first quarter of 2016.

Operating income increased $284.4 million, or 28 percent, to $1.304 billion in the first quarter of 2017, due to revenue growth, partially offset by higher operating costs related to new products.

The effective tax rate was 21.2 percent in the first quarter of 2017, compared with 17.9 percent in the first quarter of 2016. The higher effective tax rate for the first quarter of 2017 was primarily due to a net discrete tax benefit of approximately $50 million in 2016.

In the first quarter of 2017, net income and earnings per share increased 18 percent, to $1.040 billion, and $0.98, respectively, compared with $882.3 million, and $0.83, respectively, in the first quarter of 2016. The increases in net income and earnings per share were primarily driven by higher operating income, partially offset by a higher effective tax rate and lower other income.

For further detail of non-GAAP measures, see the reconciliation below as well as the Reconciliation of GAAP Reported to Selected Non-GAAP Adjusted Information table later in this press release.




First Quarter

2017

2016
% Change
Earnings (loss) per share (reported)
$
(0.10)


$
0.41

NM
Acquired in-process research and development
.81


—


Asset impairment, restructuring and other special charges
.16


.11


Amortization of intangible assets
.11


.11


Inventory step up costs associated with the acquisition of
Boehringer Ingelheim Vetmedica’s U.S. feline, canine and
rabies vaccines portfolio
.01


—


Venezuela charge
—


.19


Earnings per share (non-GAAP)
$
0.98


$
0.83

18%





Numbers may not add due to rounding.








Select Revenue Highlights






(Dollars in millions)

First Quarter




Established Pharmaceutical Products
2017

2016


% Change

Humalog
$
708.4


$
606.3


17%

Cialis
533.6


576.7


(7)%

Alimta
489.9


564.2


(13)%

Forteo
347.5


318.6


9%

Humulin
314.5


356.4


(12)%

Strattera
196.2


188.1


4%

Cymbalta
174.6


198.7


(12)%

Erbitux
154.4


168.1


(8)%

Zyprexa
147.5


212.8


(31)%

Effient
127.8


131.5


(3)%








New Pharmaceutical Products






Trulicity
372.9


143.6


160%

Cyramza
171.2


131.0


31%

Taltz
96.6


—


NM

Jardiance(a)
74.0


38.2


94%

Basaglar
46.0


10.9


321%

Lartruvo
42.1


—


NM

Portrazza
3.6


1.7


108%

Olumiant
1.9


—


NM

Subtotal
808.3


325.4


148%








Animal Health
769.4


754.6


2%








Total Revenue
5,228.3


4,865.1


7%








(a) Jardiance includes Glyxambi and Synjardy
NM – not meaningful
Numbers may not add due to rounding


Selected Established Pharmaceutical Products

Humalog

For the first quarter of 2017, worldwide Humalog revenue increased 17 percent compared with the first quarter of 2016, to $708.4 million. Revenue in the U.S. increased 24 percent, to $449.1 million, primarily driven by decreased revenue in the first quarter of 2016 resulting from changes in estimates for rebates and discounts, and to a lesser extent increased demand. Revenue outside the U.S. increased 6 percent, to $259.4 million, driven by increased volume and, to a lesser extent, higher realized prices, partially offset by the unfavorable impact of foreign exchange rates.

Cialis

For the first quarter of 2017, worldwide Cialis revenue decreased 7 percent, to $533.6 million. U.S. revenue of Cialis was $296.7 million in the first quarter, an 8 percent decrease compared with the first quarter of 2016, driven by decreased demand. Revenue of Cialis outside the U.S. decreased 6 percent, to $236.9 million, driven by decreased volume and, to a lesser extent, the unfavorable impact of foreign exchange rates, partially offset by higher realized prices.

Alimta

For the first quarter of 2017, Alimta generated worldwide revenue of $489.9 million, which decreased 13 percent compared with the first quarter of 2016. U.S. revenue of Alimta decreased 14 percent, to $227.3 million, driven by decreased demand due to competitive pressure. Revenue outside the U.S. decreased 13 percent, to $262.6 million, driven by lower realized prices, the loss of exclusivity in several countries and, to a lesser extent, the unfavorable impact of foreign exchange rates.

Forteo

First-quarter 2017 worldwide revenue for Forteo was $347.5 million, a 9 percent increase compared with the first quarter of 2016. U.S. revenue increased 20 percent, to $177.7 million, driven by higher realized prices and, to a lesser extent, wholesaler buying patterns. Revenue outside the U.S. remained flat at $169.8 million, driven by lower realized prices, offset by increased volume.

Humulin

Worldwide Humulin revenue for the first quarter of 2017 decreased 12 percent compared with the first quarter of 2016 to $314.5 million. U.S. revenue decreased 14 percent, to $205.4 million, driven by a change in the estimate in 2016 for a government rebate, which increased revenue in that period, and to a lesser extent, decreased demand. Revenue outside the U.S. decreased 6 percent, to $109.1 million, driven by lower realized prices and, to a lesser extent, the unfavorable impact of foreign exchange rates, partially offset by increased volume.

Selected New Pharmaceutical Products

Trulicity

First-quarter 2017 worldwide Trulicity revenue was $372.9 million. U.S. revenue was $296.3 million, driven by growth in the GLP-1 market and increased share of market for Trulicity. Revenue outside the U.S. was $76.6 million, primarily driven by uptake in Europe and Japan.

Cyramza

For the first quarter of 2017, worldwide Cyramza revenue was $171.2 million, an increase of 31 percent compared with the first quarter of 2016. U.S. revenue was $66.2 million, a decrease of 8 percent, driven by lower realized prices and, to a lesser extent, decreased demand due to competitive pressure. Revenue outside the U.S. was $105.1 million, an increase of 77 percent, primarily due to strong volume growth in Japan, partially offset by lower realized prices.

Taltz

For the first quarter of 2017, Taltz, a treatment for moderate-to-severe plaque psoriasis, generated worldwide revenue of $96.6 million. U.S. revenue was $87.8 million, an increase of $28.4 million compared with the fourth quarter of 2016, reflecting strong launch uptake.

Jardiance

The company’s worldwide Jardiance revenue during the first quarter of 2017 was $74.0 million, an increase of 94 percent compared with the first quarter of 2016. U.S. revenue increased 60 percent, to $47.7 million, driven by increased share of market for Jardiance and growth in the SGLT2 class. Revenue outside the U.S. was $26.2 million. Jardiance is part of the company’s alliance with Boehringer Ingelheim, and Lilly reports as revenue a portion of Jardiance’s gross margin.

Basaglar

For the first quarter of 2017, Basaglar generated worldwide revenue of $46.0 million. U.S. revenue was $22.0 million. Basaglar is part of the company’s alliance with Boehringer Ingelheim, and Lilly reports as revenue total sales, with payments made to Boehringer Ingelheim for its portion of the gross margin reported as cost of sales.

Lartruvo

For the first quarter of 2017, Lartruvo, a treatment in combination with doxorubicin for a subset of adult patients with advanced soft tissue sarcoma, generated worldwide revenue of $42.1 million. U.S. revenue was $38.1 million, an increase of $26.7 million compared with the fourth quarter of 2016.

Olumiant

For the first quarter of 2017, Olumiant, a treatment for moderate-to-severe rheumatoid arthritis, generated worldwide revenue of $1.9 million, reflecting initial sales in Germany.

Animal Health

In the first quarter of 2017, worldwide animal health revenue totaled $769.4 million, an increase of 2 percent compared with the first quarter of 2016. Worldwide food animal revenue decreased 3 percent, to $508.1 million, driven by lower worldwide volume due to continued economic pressure in the dairy market and customer buying patterns. Worldwide companion animal revenue increased 13 percent, to $261.3 million, driven by the inclusion of $40.8 million in revenue from the acquisition of Boehringer Ingelheim Vetmedica’s U.S. feline, canine and rabies vaccine portfolio, partially offset by worldwide competitive pressure.

2017 Financial Guidance

Earnings per share for 2017 are being revised to be in the range of $2.60 to $2.70 on a reported basis, due to severance costs incurred as a result of actions taken to reduce the company’s cost structure. Earnings per share for 2017 are being reaffirmed to be $4.05 to $4.15 on a non-GAAP basis.




2017
Expectations
% Change
from 2016
Earnings per share (reported)
$2.60 to $2.70
1% to 5%
Acquired in-process research and development charge related to
the acquisition of CoLucid Pharmaceuticals
.81

Amortization of intangible assets (1)
.44

Asset impairment, restructuring and other special charges,
including Novartis Animal Health integration costs
.17

Inventory step-up costs associated with the acquisition of
Boehringer Ingelheim Vetmedica’s U.S. feline, canine and rabies
vaccines portfolio (1)
.02

Earnings per share (non-GAAP)
$4.05 to $4.15
15% to 18%
(1) Subject to acquisition accounting adjustments


Numbers may not add due to rounding




The company still anticipates 2017 revenue between $21.8 billion and $22.3 billion. Excluding the impact of foreign exchange rates, the company expects revenue growth from animal health products and a number of established pharmaceutical products including Trajenta, Forteo and Humalog, as well as higher revenue from new products including Trulicity, Taltz, Basaglar, Cyramza, Jardiance and Lartruvo.

Marketing, selling and administrative expenses are still expected to be in the range of $6.4 billion to $6.6 billion. Research and development expenses are still expected to be in the range of $4.9 billion to $5.1 billion.

The 2017 tax rate is still expected to be approximately 24.5 percent on a reported basis and 22.0 percent on a non-GAAP basis.

The following table summarizes the company’s 2017 financial guidance:




2017 Guidance

Prior

Revised
Revenue
$21.8 to $22.3 billion

Unchanged




Gross Margin % of Revenue (reported)
Approx. 73.5%

Unchanged
Gross Margin % of Revenue (non-GAAP)
Approx. 77.0%

Unchanged




Marketing, Selling & Administrative
$6.4 to $6.6 billion

Unchanged




Research & Development
$4.9 to $5.1 billion

Unchanged




Other Income/(Expense)
$0 to $100 million

Unchanged




Tax Rate (reported)
Approx. 24.5%

Unchanged
Tax Rate (non-GAAP)
Approx. 22.0%

Unchanged




Earnings per Share (reported)
$2.69 to $2.79

$2.60 to $2.70
Earnings per Share (non-GAAP)
$4.05 to $4.15

Unchanged




Capital Expenditures
Approx. $1.2 billion

Unchanged




Non-GAAP adjustments are consistent with the earnings per share table above.

On April 24, 2017 The biopharmaceutical company MOLOGEN AG (ISIN DE0006637200; Frankfurt Stock Exchange Prime Standard: MGN) reported the key results of the exploratory phase II IMPULSE study (Press release, Mologen, APR 24, 2017, View Source [SID1234518676]). The randomized study evaluated the efficacy and safety of lefitolimod in patients with extensive-disease small-cell lung cancer (SCLC). IMPULSE shows positive results regarding overall survival (OS) in two subgroups of patients in comparison to the control group (standard therapy). Additional, potentially promising subgroups will be identified. The results of this SCLC study provide significant guidance for defining patient populations that, even beyond this study, are most likely to benefit from the immune surveillance reactivator lefitolimod, even though in this highly challenging indication the primary endpoint OS was not met in the overall study population.

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"Lung cancer, and especially small-cell lung cancer, is an indication for which the benefit of current standard treatment is very limited. We are therefore very pleased to see initial evidence of clinical efficacy for lefitolimod in small-cell lung cancer, an indication known for its setbacks in other drug development programs," said Dr Mariola Soehngen, CEO of MOLOGEN AG. "The data of the IMPULSE study, especially from the two identified subgroups, show that lefitolimod has the potential to become an important treatment option – also for patients with a disease as difficult to treat as small-cell lung cancer. Notably, these positive study results will be an important asset in the ongoing partnering discussions."

The IMPULSE study shows positive results in two pre-defined and clinically relevant subgroups of patients. Notably, a strong overall survival (OS) benefit was shown in comparison to the control arm (local standard of care) in patients with a low count of activated B cells (hazard ratio 0.59, 95% confidence interval 0.29-1.21), an important immune parameter. Moreover, a benefit was seen in patients with reported Chronic Obstructive Pulmonary Disease (COPD), a frequent underlying disease (hazard ratio 0.54, 95% confidence interval 0.21-1.38).

The safety profile of lefitolimod is favorable. The most common adverse events in the IMPULSE population were cough, asthenia, headache, nausea, and back pain. Adverse events may also be due to underlying diseases and/or adjunctive therapy.

"We have seen promising efficacy signals in subgroups of patients in this very difficult-to-treat- indication. We are committed to further analyze the data and to continue the development of lefitolimod in small-cell lung cancer, where there are no better current treatment options than chemotherapy. Therefore, an important medical need exists for new and/or complementary combination treatment alternatives. Moreover, it would also be helpful to evaluate lefitolimod in patients with SCLC in combination with other immuno-oncological drugs," said Dr Ronald Carter, Acting CMO of MOLOGEN AG.

The present findings from IMPULSE provide additional key insights into the role of TLR9 agonists in the treatment of cancer, and confirm there is significant opportunity to improve outcomes for patients in this therapeutic area.

A more extensive evaluation of the IMPULSE data is currently ongoing. The full IMPULSE study results will be presented at international scientific conferences.

MOLOGEN’s ongoing development programs, especially the pivotal IMPALA study, are running independently from these study results, given these are different indications.

Three more clinical studies with lefitolimod

Further to the IMPULSE study, lefitolimod is currently being evaluated in the pivotal phase III IMPALA study for first-line maintenance treatment of metastatic colorectal cancer (mCRC); recruitment for this trial is expected to be finalized soon. Furthermore, a phase I study of lefitolimod in combination with the commercially available checkpoint inhibitor Yervoy (ipilimumab) in other solid tumors is being conducted in collaboration with MD Anderson Cancer Center, Texas. In addition, lefitolimod is also being investigated in a phase I study in HIV-infected patients (TEACH). Top-line results are expected in summer 2017.

Background to the IMPULSE small-cell lung cancer (SCLC) study

The trial titled "Randomized Clinical Study of Maintenance Therapy with Immunomodulator MGN1703 in patients with Extensive Disease Small Cell Lung Cancer after Platinum-Based First-Line Therapy" (IMPULSE study) is an explorative study and has overall survival as the primary endpoint. It compares lefitolimod (MGN1703) versus standard therapy (chemotherapy). The study included 102 patients suffering from extensive-disease small-cell lung cancer, and showing at least partial response to four cycles of first-line chemotherapy (n=102). They were randomized in a ratio of 3:2 to switch-maintenance therapy with lefitolimod (60mg injected subcutaneously twice weekly) or standard therapy until disease progression.

There will be a final read-out probably in the first quarter of 2018, approximately 24 months following the recruitment of the last patient.

Small-cell lung cancer (SCLC)

Lung cancer is one of the most common cancers. The estimated number of new lung cancer cases per year is around 230,000 in the U.S. and in Europe more than 400,000 with an estimated number of deaths per year of approximately 170,000 and more than 350,000 respectively.

The two main types are non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). SCLC is a fast-growing type of lung cancer that usually spreads more quickly than NSCLC and represents approximately 15-20% of all lung cancer cases.

When first diagnosed, approx. 60-80% of SCLC-patients already have distant metastases or extensive local spreading of the disease called "extensive-disease" SCLC. The prognosis for extensive-disease SCLC is still very poor: median overall survival (OS) is less than 12 months and only few patients survive more than two years. Thus, there is a high unmet medical need for new treatment options.

For more information on the clinical development program including IMPULSE, IMPALA, the combination study, and TEACH please visit www.clinicaltrials.gov.