On October 20, 2016 – Actelion Ltd (SIX: ATLN) reported its results for the first nine months of 2016 (Press release, Actelion, OCT 20, 2016, View Source [SID1234515938]). Schedule your 30 min Free 1stOncology Demo! OPERATING HIGHLIGHTS
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Strong Opsumit (macitentan) trajectory and quarterly net new patient gains sustained
Excellent US launch momentum for Uptravi (selexipag) – enhanced by launches in Germany and the Netherlands
Uptravi (selexipag) approvals in Switzerland and Japan (by Nippon Shinyaku) in Q3
First all-oral combination therapy with ponesimod and dimethyl fumarate (Tecfidera) to be evaluated for patients with relapsing multiple sclerosis
FINANCIAL HIGHLIGHTS
Sales growing to CHF 1,785 million (+14% at CER) – New PAH products surpass Tracleer for the first time
Opsumit sales grow to CHF 596 million (+63% at CER)
Uptravi sales reach CHF 160 million after just 9 months on the market
US GAAP operating income grows to CHF 660 million (+17% at CER)
Core operating income grows to CHF 781 million (+14% at CER)
2016 financial guidance upgraded: core operating income growth in the mid-teen percentage range, at constant exchange rates and barring unforeseen events
% variance
in CHF million
(except for per share data) 9M 2016 9M 2015 in CHF at CER(1)
US GAAP results
Net revenue 1,791 1,525 17% 14%
Operating income 660 533 24% 17%
Net income 581 452 29% 21%
Diluted EPS 5.37 3.99 35% 27%
Core performance(2)
Product sales 1,785 1,522 17% 14%
Core operating income 781 651 20% 14%
Core net income 691 560 23% 17%
Core diluted EPS 6.38 4.94 29% 23%
Cash flow 9M 2016 9M 2015
Operating cash flow 695 533
Capital expenditure (45) (17)
Free cash flow 6 (506)
Net cash position as of 30 September 411 698
CER percentage changes are calculated by reconsolidating both the 9M 2015 and 9M 2016 results at constant currencies (the average monthly exchange rates for 9M 2015).
Actelion continues to measure, report and issue guidance on its core operating performance, which management believes more accurately reflects the underlying business performance. The Group believes that these non-GAAP financial measurements provide useful supplementary information to investors. These non-GAAP measures are reported in addition to, not as a substitute for, US GAAP financial performance.
Jean-Paul Clozel, MD, Chief Executive Officer, commented: "Once again, we have delivered a very strong performance across all areas of our business. I am particularly happy with the very positive feedback we receive from physicians prescribing Uptravi. We have also made considerable progress advancing our innovative pipeline, highlighted by the recent initiation of the combination study with ponesimod in relapsing multiple sclerosis. In summary, the transformation of the company is well under way."
Otto Schwarz, Chief Operating Officer, commented: "We continue to be extremely pleased with the transformation of our PAH portfolio. For the first time, in the third quarter, more than 50% of our sales came from our new outcome-based PAH portfolio. The strong uptake of Uptravi in the US continued during the third quarter, enhanced by a strong early trajectory in Germany, resulting in a total of over 1,800 patients benefiting from this novel oral therapy at the end of September 2016."
André C. Muller, Chief Financial Officer, commented: "The excellent commercial performance has enabled us to increase our R&D effort to advance both the late and earlier stage pipeline, whilst continuing to deliver strong earnings growth. Our focus on the bottom line, coupled with strong sales enables us to increase guidance. Barring unforeseen events, we now expect 2016 core operating income growth in the mid-teen percentage range at constant exchange rates."
SALES UPDATE
Actelion’s strong performance continued during the third quarter of 2016 driven by the outstanding Uptravi launch in the US and Opsumit’s ongoing growth dynamics. For the first time, during the third quarter of 2016, sales of the company’s outcome-based PAH portfolio, Opsumit, Uptravi and Veletri, exceeded 50% of total sales, demonstrating the extent of the transformation of the PAH franchise.
In the US, sales increased by 23% at CER, driven by the strong Uptravi launch, continued Opsumit momentum and ERA market share gains. European sales were at the same level as 2015, despite increased Opsumit uptake and Tracleer use in the digital ulcer indication, but mitigated by continued pricing pressure and market erosion from generics, particularly in Spain. Sales in Japan increased by 20% at CER, mostly driven by very strong sales of Opsumit (launched in June 2015), Tracleer in digital ulcer indication, Veletri and Zavesca (Japanese trade name Brazaves).
Comparing average exchange rates for the first nine months of 2016 to the first nine months of 2015, the Swiss franc weakened, mostly against the US dollar, euro and Japanese yen, resulting in a positive currency variance of 54 million Swiss francs.
Sales by product – 9M 2016
% variance
in CHF millions 9M 2016 9M 2015 in CHF at CER
Opsumit 596 354 68 63
Tracleer 790 934 -15 -18
Uptravi 160 - nm* nm
Veletri 71 60 18 13
Ventavis 58 81 -28 -31
Valchlor 26 19 34 30
Zavesca 78 68 15 13
Others 6 5 12 14
Total product sales 1,785 1,522 17 14
*nm = not meaningful
Sales by product – Q3 2016
% variance
in CHF millions Q3 2016 Q3 2015 in CHF at CER
Opsumit 218 147 49 45
Tracleer 244 289 -16 -18
Uptravi 70 - nm nm
Veletri 23 22 7 2
Ventavis 15 24 -39 -40
Valchlor 8 7 10 8
Zavesca 26 24 11 9
Others 2 2 1 -1
Total product sales 606 514 18 15
Sales by region – 9M 2016
% variance
in CHF millions 9M 2016 9M 2015 in CHF at CER
United States 964 766 26 23
Europe* 485 475 2 0
Japan 182 132 38 20
Rest of the world 155 149 4 6
Total product sales 1,785 1,522 17 14
*Europe = EU28 and Switzerland
Sales by region – Q3 2016
% variance
in CHF millions Q3 2016 Q3 2015 in CHF at CER
United States 325 271 20 18
Europe* 163 157 3 3
Japan 66 45 45 20
Rest of the world 52 40 30 29
Total product sales 606 514 18 15
*Europe = EU28 and Switzerland
PAH FRANCHISE
Opsumit
Sales of Opsumit (macitentan) amounted to 596 million Swiss francs for the first nine months of 2016, an increase of 63% at CER compared to the first nine months of 2015. This increase continues to be driven by new patient starts with commercial availability in over 30 countries. The continued increase in patients benefitting from Opsumit is driven by referral of treatment-naïve patients together with increased use in combination with PDE-5 inhibitors, and some upgrades from Tracleer, notably in Japan.
Uptravi
Sales of Uptravi (selexipag) amounted to 160 million Swiss francs for the first nine months of 2016. Since the US launch at the beginning of January 2016, patient demand has continued to increase with sales of 126 million Swiss francs (excluding initial inventory build of 30 million Swiss francs). For the third quarter, revenues from patient demand in the US amounted to 66 million Swiss francs compared to 45 million Swiss francs in the second quarter and 15 million Swiss francs in the first quarter of 2016. Uptravi was successfully launched in Germany in mid-June 2016 with sales reaching 3 million Swiss francs in an underdeveloped market in terms of prostacyclin usage. At the end of September, about 1,800 patients were using Uptravi globally.
During the third quarter 2016, Uptravi was approved in Switzerland and Japan (where it will be co-promoted by Nippon Shinyaku, who will record the sales) pending pricing and reimbursement approval.
Tracleer
Sales of Tracleer (bosentan) amounted to 790 million Swiss francs for the first nine months of 2016, a decrease of 18% at CER compared to the first nine months of 2015, equally driven by lower underlying volume and average price. The decrease is mainly due to lower referrals of new patients as well as switches in countries where Opsumit is available, increased generic competition, notably in Spain, continued pricing pressure in Europe and lower inventories in the US.
Tracleer sales were supported by the digital ulcer indication in Europe and Japan and continued solid demand in markets where Opsumit is not yet available.
Following the Pediatric Investigation Plan (PIP) compliance statement from the European Committee for Medicinal Products for
Human Use (CHMP), applications for extension of the Supplementary Protection Certificate (SPC) were granted in 19 EU countries until the end of August 2017.
Veletri
Sales of Veletri (epoprostenol for injection) amounted to 71 million Swiss francs for the first nine months of 2016, an increase of 13% at CER compared to the first nine months of 2015. This increase was mostly driven by successful market penetration, notably in France, and also Italy, Spain and UK. Demand in Japan remained solid, but sales were impacted by a 12% price cut effective from 01 March 2016.
Ventavis
Sales of Ventavis (iloprost) amounted to 58 million Swiss francs for the first nine months of 2016, a decrease of 31% at CER, compared to the first nine months of 2015. This is due to the competitive environment, including the availability of Uptravi. Underlying units decreased by 18%.
SPECIALTY PRODUCTS
Valchlor
Sales of Valchlor (mechlorethamine) amounted to 26 million Swiss francs for the first nine months of 2016, an increase of 30% at CER, compared to the first nine months of 2015. In the US, the company is continuing its efforts to establish Valchlor as an option in the treatment algorithm for early-stage mycosis fungoides, a type of Cutaneous T-Cell Lymphoma (MF-CTCL). In France, patients benefited from the drug under a temporary nominative authorization for use ("ATU") program initiated during the second half of 2014.
The regulatory dossier is currently under review with the European Medicines Agency (under the trade name Ledaga).
Zavesca
Sales of Zavesca (miglustat) amounted to 78 million Swiss francs for the first nine months of 2016, an increase of 13% at CER compared to the first nine months of 2015. Sales in the US were strong due to a relatively low prior year base as a consequence of last year’s inventory adjustment. In Europe, sales decreased by 2% mainly due to the launch of generic miglustat (approved for the type 1 Gaucher disease indication only). Sales in Japan were 16% higher, driven by increased patient demand in the Niemann-Pick type C indication.
The global number of patients receiving therapy grew by 7% compared to the first nine months of 2015, driven by a 16% increase in Niemann-Pick type C demand.
CLINICAL DEVELOPMENT PIPELINE
The pipeline continued to strengthen with substantial progress made with several compounds:
In the third quarter, Actelion announced the initiation of the Phase III POINT study, which investigates the use of combination therapy with ponesimod, an orally active, selective sphingosine-1-phosphate receptor 1 (S1P1) immunomodulator, and dimethyl fumarate (Tecfidera) for patients with relapsing multiple sclerosis (RMS). The POINT study – which will be conducted under a Special Protocol Assessment (SPA) agreement with the FDA – is the first to assess the concurrent administration of two oral therapies in MS with the objective to improve disease control in this progressive, debilitating neurological disorder. Ponesimod is also being studied in the double blind long-term extension of the Phase II study as well as in the Phase III study OPTIMUM to compare the efficacy and safety of ponesimod with teriflunomide in patients with RMS. Enrollment for the OPTIMUM study is on target to be completed around the end of 2016.
Also in the third quarter, the company advanced its new dual orexin receptor antagonist (DORA) into Phase II development in patients with insomnia. The Phase II program consists of two studies, one in adult and one in elderly patients, and is designed to evaluate the effect of Actelion’s DORA versus placebo on sleep maintenance and sleep initiation, as well as next-day residual effect and next-day performance. The study in adults also includes a zolpidem reference arm. The decision to move into a Phase II program was based on excellent data collected from the preclinical and Phase I clinical program, as well as a thorough understanding of the potential of dual orexin receptor antagonism on sleep efficacy and architecture.
With macitentan (Opsumit), we are entering into a pediatric study, TOMORROW, to evaluate the effect of macitentan on delaying disease progression in children with PAH using a pediatric formulation of macitentan. The global trial design has received endorsement from the US FDA (through a pediatric Written Request) and in the EU (through a Paediatric Investigation Plan). Enrollment is expected to start around the end of 2016.
A Phase II study, MERIT, assesses the efficacy, safety and tolerability of macitentan in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). The study is on schedule to deliver results by the end of the year.
Enrollment of participants in the ongoing Phase III program IMPACT investigating cadazolid treatment in patients suffering from Clostridium difficile-associated diarrhea is progressing well and is on target to be completed around the end of 2016.
Compound Indication Study Status
Phase III Cadazolid Clostridium difficile-associated diarrhea IMPACT Ongoing
Macitentan Eisenmenger syndrome MAESTRO Ongoing
Macitentan Pediatric PAH TOMORROW Initiating
Ponesimod
Multiple sclerosis OPTIMUM Ongoing
Ponesimod Multiple sclerosis POINT Initiating
Phase II Cenerimod Systemic lupus erythematosus - Ongoing
Clazosentan Reversal of vasospasm associated with aneurysmal subarachnoid hemorrhage REVERSE Ongoing
Dual Orexin Receptor Antagonist Insomnia - Ongoing
Endothelin Receptor Antagonist Specialty cardiovascular disorders - Ongoing
Macitentan Chronic thromboembolic pulmonary hypertension MERIT Ongoing
Macitentan Combined pre- and post-capillary pulmonary hypertension MELODY Complete
Ponesimod Graft-versus-host disease - Ongoing
Phase Ib Lucerastat Fabry disease - Complete
Phase I New Chemical Entity Cardiovascular disorders - Ongoing
New Chemical Entity Inflammatory disorders - Ongoing
Selective Orexin 1 Receptor Antagonist Neurological disorders - Ongoing
T-type Calcium Channel Blocker Neurological disorders - Ongoing
RESULTS DAY CENTER
Investor community: To make your job easier, we provide links to all relevant documentation, such as a full financial review, reconciliation US-GAAP to Core results and geographical breakdown by product, from the Results Day Center on our corporate website: www.actelion.com/results-day-center.
Roche delivers good sales growth in the first nine months of 2016
On October 20, 2016 Roche reported good sales growth in the first nine months of 2016 (Press release, Hoffmann-La Roche , OCT 20, 2016, View Source [SID1234515921]). Schedule your 30 min Free 1stOncology Demo! Group sales increase 4%1 at constant exchange rates, 6% in Swiss francs
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Pharmaceuticals Division sales up 4%, driven by oncology and immunology medicines
Diagnostics Division sales grow 7%, primarily due to immunodiagnostic products
US FDA approves Tecentriq, the first anti-PD-L1 cancer immunotherapy for metastatic non-small cell lung cancer
Successful launch of cobas e 801, high-throughput immunodiagnostic module
For the eighth year running, Roche ranked as the most sustainable healthcare company in the Dow Jones Sustainability Index (DJSI)
Outlook for 2016 confirmed
Commenting on the Group’s first nine months, Roche CEO Severin Schwan said: "We had continued good sales growth in both Pharmaceuticals and Diagnostics driven by our newly launched products, and our product pipeline is developing very well. Our cancer immunotherapy medicine Tecentriq has been performing strongly since May, when it was first approved in the US for people with advanced bladder cancer, and it has just received US FDA approval for previously treated metastatic non-small cell lung cancer. Based on our performance so far, I am confident that we will meet our full-year targets for 2016."
Group
Both divisions showed continued growth
Group sales increased 4% to CHF 37.5 billion. Sales in the Pharmaceuticals Division were up 4% to CHF 29.1 billion, driven by demand for breast cancer medicines Perjeta and Herceptin as well as for Actemra/RoActemra for rheumatoid arthritis. Sales in the US rose 3%, led by three immunology treatments Xolair, Esbriet and Actemra/RoActemra, as well as Activase/TNKase, and Perjeta and Herceptin for HER2-positive breast cancer. The recently launched medicines Tecentriq in bladder cancer and Alecensa in lung cancer have had a strong uptake. US growth was partly offset by a decline in sales of Tamiflu, Lucentis, Avastin and Tarceva. In Europe, sales increased 5% with Perjeta, Actemra/RoActemra and MabThera/Rituxan recording strong growth, especially in Germany and France. In the International region, the 4% growth was driven by the strategic cancer medicines portfolio. In Japan, sales were stable; mandated price cuts for reimbursed products were compensated by strong growth from Alecensa, HER2 cancer medicines and Actemra/RoActemra.
Sales in the Diagnostics Division grew strongly (+7%) to CHF 8.4 billion. All regions contributed to this growth, particularly Asia-Pacific (+17%). Professional, Molecular and Tissue Diagnostics experienced continued good sales development. Diabetes Care sales continue to be impacted by challenging market conditions, especially in North America.
Confirming data for key investigational Roche medicines
Two Roche medicines were granted breakthrough therapy designations (BTD) by the US FDA in October. BTD was granted to Actemra/RoActemra for giant cell arteritis (GCA), a chronic, potentially life-threatening autoimmune condition. In addition, Alecensa received BTD for the treatment of adult patients with advanced ALK-positive non-small cell lung cancer (NSCLC) who have not received prior treatment with an ALK inhibitor. Also in October, the FDA approved the Lucentis prefilled syringe as a new method of administering the medicine to people with wet age-related macular degeneration and to people with macular edema after retinal vein occlusion.
In September, Roche presented new post-hoc analyses from three pivotal Ocrevus (ocrelizumab) studies at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The new data showed that Ocrevus consistently increased disease control both in patients with the relapsing form of multiple sclerosis and in those with the primary progressive form.
At the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) annual meeting in October, Roche presented results from the phase III OAK trial with Tecentriq in metastatic NSCLC. The study met its primary endpoint, having established a survival benefit over chemotherapy, even in people with low or no observed levels of PD-L1 expression. These results add to the growing body of evidence that supported the FDA approval of Tecentriq as a new treatment for specific types of advanced NSCLC. In addition to OAK, Roche has seven phase III lung studies underway evaluating Tecentriq alone or in combination with other treatments in patients with early and advanced stages of lung cancer.
Portfolio progress in Diagnostics
In August, the FDA granted a premarket clearance and CLIA (Clinical Laboratory Improvement Amendments) waiver for the cobas Influenza A/B & RSV test for use on the cobas Liat System. This test also identifies the Respiratory Syncytial Virus (RSV), which causes more than 80% of acute lower respiratory tract infections in infants under one year old. The FDA also issued an Emergency Use Authorization for the LightMix Zika rRT-PCR test for use in patients meeting clinical and/or epidemiological criteria developed by the Center for Disease Control. These tests further expand the rich menu of Roche products.
Also in August, the Accu-Chek Guide was launched in the EU. This next-generation blood glucose monitoring system is designed to make everyday blood glucose monitoring easier for people with diabetes. The Accu-Chek Guide system also provides advanced accuracy, which enables reliable diabetes management.
Roche the most sustainable healthcare company
The Dow Jones Sustainability Index (DJSI) recognised Roche as the most sustainable company in the healthcare industry for the eighth consecutive year. This year’s DJSI assessment emphasised that by focusing on access to healthcare, compliance and transparency, a diverse work culture and collaboration with a variety of partners, Roche is committed to creating value for all its stakeholders.
MorphoSys Receives Clinical Milestone for Start of Phase 1 Trial with Novel Cancer Antibody
On October 20, 2016 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported that it has received a milestone payment from Novartis in connection with the initiation of a phase 1 clinical trial with a novel HuCAL antibody. The antibody will be tested in the field of cancer. Financial details were not disclosed (Press release, MorphoSys, OCT 19, 2016, View Source [SID1234515930]).
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"This is the 13th therapeutic antibody based on MorphoSys’s technologies that Novartis is evaluating in clinical trials, thus making our collaboration one of the most successful antibody alliances in our industry" commented Dr. Marlies Sproll, Chief Scientific Officer of MorphoSys AG. "During the course of this year, the MorphoSys pipeline has further matured and currently includes more programs in clinical trials than ever before. This reflects the great value of both MorphoSys’s technology and the resulting products, in our partnered as well as proprietary pipeline."
MorphoSys’s clinical pipeline now comprises 28 clinical programs. Two of them are in phase 3, 15 in phase 2 and 11 in phase 1. Novartis has currently 13 HuCAL antibodies in clinical development, of which six are in phase 2 and seven in phase 1.
FDA Approves Lilly’s LARTRUVO™ (olaratumab) in Combination with Doxorubicin for Soft Tissue Sarcoma
On October 19, 2016 Eli Lilly and Company (NYSE: LLY) reported that the U.S. Food and Drug Administration (FDA) has granted approval of LARTRUVO (olaratumab injection, 10 mg/mL), in combination with doxorubicin, for the treatment of adults with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery (Press release, Eli Lilly, OCT 19, 2016, View Source [SID1234515929]). LARTRUVO’s indication is approved under Accelerated Approval, and is based on data from the Phase 2 portion of the pivotal JGDG trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. LARTRUVO, in combination with doxorubicin, is the first FDA-approved front-line therapy for STS in four decades. The confirmatory Phase 3 trial, ANNOUNCE, is fully enrolled.
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"LARTRUVO represents an important step forward in soft tissue sarcoma treatment," said William D. Tap, M.D., chief of the sarcoma medical oncology services at Memorial Sloan Kettering Cancer Center in New York and the principal investigator of the JGDG registration trial. "We are pleased with this approval, which will provide patients with a treatment option that offers new hope in their battle against this difficult disease."
Soft tissue sarcoma is a complex disease with multiple subtypes, making it hard to diagnose and difficult to treat. For decades, there have been no first-line therapeutic advancements for STS that have improved overall survival (OS). According to the American Cancer Society, in 2015, there were an estimated 12,000 new STS cases diagnosed and nearly 5,000 deaths in the U.S. alone, representing an unmet medical need.
LARTRUVO is the first monoclonal antibody approved to treat STS. It also received Fast Track, Orphan Drug and Breakthrough Therapy designations from the FDA for this indication, and was reviewed and approved under the FDA’s Accelerated Approval program. This program allows for earlier approval of drugs that treat serious conditions and that fill an unmet medical need.
"The approval of LARTRUVO is based on an encouraging and positive study for patients, and represents progress in soft tissue sarcoma treatment. For the first time in four decades, we now have a combination regimen – LARTRUVO and doxorubicin – that offers progress over doxorubicin alone in the front-line setting, by improving overall survival for people with soft tissue sarcoma," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "This continues our commitment to discovering new ways to treat cancer, including for people who have rare types of cancer."
"The entire sarcoma patient community is excited to have an innovative medicine approved for the treatment of advanced soft tissue sarcoma," said Bert E. Thomas IV, PhD, MBA, CEO of the Sarcoma Foundation of America. "We are confident that the approval of LARTRUVO may help these patients live longer."
The approval of LARTRUVO is based on the results of JGDG, an open-label, randomized, active-controlled study of 133 patients, which compared LARTRUVO, in combination with doxorubicin chemotherapy, to doxorubicin alone in patients with STS with a histologic subtype for which an anthracycline-containing regimen was appropriate and which is not amenable to curative treatment with surgery or radiotherapy. The efficacy outcome measures were OS, progression-free survival (PFS), and objective response rate (ORR).
Median OS was improved by 11.8 months in patients randomized to receive LARTRUVO plus doxorubicin compared to patients randomized to doxorubicin alone, and was statistically significant. Median OS was 26.5 months (95% CI: 20.9, 31.7) on the LARTRUVO-doxorubicin arm compared to 14.7 months (95% CI: 9.2, 17.1) on the doxorubicin-only arm (stratified hazard ratio [HR], 0.52; 95% CI: 0.34, 0.79, < 0.05). The study met its prespecified protocol-defined endpoint for PFS. Patients treated on the LARTRUVO and doxorubicin arm achieved 8.2 months (95% CI: 5.5, 9.8) of median PFS compared to 4.4 months (95% CI: 3.1, 7.4) on the doxorubicin-only arm (stratified hazard ratio [HR], 0.74; 95% CI: 0.46, 1.19), based on independent review. The number of events at the time of analysis was 37 (56%) on the LARTRUVO-doxorubicin arm and 34 (51%) on the doxorubicin-only arm. The number of deaths at the time of analysis was 39 (59%) on the LARTRUVO-doxorubicin arm and 52 (78%) on the doxorubicin-only arm. Objective response rate (ORR), based on independent review and defined as complete response (CR) plus partial response (PR), was also assessed with an ORR of 18.2 percent (95% CI: 9.8, 29.6) (CR, 4.5%; PR, 13.6%) on the LARTRUVO-doxorubicin arm and 7.5 percent (95% CI: 2.5, 16.6) (CR, 1.5%; PR, 6%) on the doxorubicin-only arm.
The labeling for LARTRUVO contains Warnings and Precautions for infusion-related reactions and embryo-fetal toxicity. The most commonly reported adverse reactions (all grades) occurring in ≥20 percent of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were nausea (73% vs 52%), fatigue (69% vs 69%), musculoskeletal pain (64% vs 25%), mucositis (53% vs 35%), vomiting (45% vs 19%), diarrhea (34% vs 23%) and headache (20% vs 9%). The most common laboratory abnormalities (all grades) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were lymphopenia (77% vs 73%), neutropenia (65% vs 63%), thrombocytopenia (63% vs 44%), hyperglycemia (52% vs 28%), elevated aPTT (33% vs 13%), hypokalemia (21% vs 15%) and hypophosphatemia (21% vs 7%). Febrile neutropenia was reported in 13% of LARTRUVO plus doxorubicin-treated patients versus 12% of doxorubicin-treated patients.
Adverse reactions resulting in permanent discontinuation of LARTRUVO occurred in 8% (5/64) of patients. The most common adverse reaction leading to LARTRUVO discontinuation was infusion-related reaction (3%). Dose reductions of LARTRUVO for adverse reactions occurred in 25% (16/64) of patients; the most common adverse reaction leading to dose reduction was Grade 3 or 4 neutropenia (20%). Dose delays of LARTRUVO for adverse reactions occurred in 52% (33/64) of patients; the most common adverse reactions resulting in dose delays were neutropenia (33%), thrombocytopenia (8%) and anemia (5%). See the full Important Safety Information at the end of this press release and the Prescribing Information.
Lilly is committed to helping patients access LARTRUVO and offers support programs for qualified uninsured, underinsured and insured patients who receive LARTRUVO for its FDA-approved indication and who may need assistance with their out-of-pocket prescription medication costs, including a co-pay program where qualified patients pay no more than $25 per infusion. Patients and healthcare professionals with questions about LARTRUVO should contact The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979) or visit www.lilly.com.
About LARTRUVO (olaratumab)
LARTRUVO is a platelet-derived growth factor receptor alpha (PDGFR-α) blocking antibody that specifically binds PDGFR-α and prevents receptor activation. LARTRUVO exhibits in vitro and in vivo anti-tumor activity against selected sarcoma cell lines and disrupted the PDGFR-α signaling pathway in in vivo tumor implant models. Information about additional clinical trials for LARTRUVO in sarcoma can be found at ClinicalTrials.gov (in the search box on the home page, type in "olaratumab").
A Phase 3 trial of LARTRUVO and doxorubicin in advanced STS is fully enrolled (ClinicalTrials.gov Identifier: NCT02451943).
About the JGDG Trial
JGDG was an open-label, randomized, active-controlled study that compared LARTRUVO, in combination with doxorubicin chemotherapy, to doxorubicin alone in patients with unresectable, soft tissue sarcoma (STS).
The study enrolled 133 doxorubicin-naïve patients with STS with a histologic subtype for which an anthracycline-containing regimen was appropriate and which is not amenable to curative treatment with surgery or radiotherapy. Sixty-six patients with an ECOG performance status of 0 – 2 were randomized to the LARTRUVO-doxorubicin arm and 67 to the doxorubicin-only arm.
Patients were randomized to receive LARTRUVO at 15 mg/kg as an intravenous infusion on day one of each 21-day cycle in combination with 75 mg/m2 doxorubicin, and LARTRUVO only on day eight. Doxorubicin was administered following LARTRUVO infusion on day one of each 21-day cycle for up to eight cycles. After doxorubicin was discontinued, patients on the LARTRUVO plus doxorubicin arm without evidence of disease progression or unacceptable toxicity could continue to receive LARTRUVO monotherapy until disease progression. All patients received the cardioprotectant dexrazoxane prior to doxorubicin in cycles five to eight.
About Sarcomas
Sarcomas are a diverse and relatively rare type of cancer that usually develop in the connective tissue of the body, which include fat, blood vessels, nerves, bones, muscles, deep skin tissues and cartilage. Soft tissue sarcoma is a complex disease with multiple subtypes, making it very hard to diagnose and difficult to treat. For decades, there have been no front-line therapeutic advancements for STS that have improved overall survival. According to the American Cancer Society, in 2015, there were an estimated 12,000 new STS cases diagnosed and nearly 5,000 deaths in the U.S. alone.
INDICATION
LARTRUVO is indicated, in combination with doxorubicin, for the treatment of adult patients with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.
This indication is approved under Accelerated Approval. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.
IMPORTANT SAFETY INFORMATION FOR LARTRUVO
Warnings and Precautions
Infusion-Related Reactions
Infusion-related reactions (IRR) occurred in 70 (14%) of 485 patients who received at least one dose of LARTRUVO across clinical trials. For 68 of these 70 patients (97%), the first occurrence of IRR was in the first or second cycle. Grade ≥3 IRR occurred in 11 (2.3%) of 485 patients, with one (0.2%) fatality. Symptoms of IRR included flushing, shortness of breath, bronchospasm, or fever/chills, and in severe cases symptoms manifested as severe hypotension, anaphylactic shock, or cardiac arrest. Infusion-related reactions required permanent discontinuation in 2.3% of patients and interruption of infusion in 10% of patients. All 59 patients with Grade 1 or 2 IRR resumed LARTRUVO; 12 (20%) of these patients had a Grade 1 or 2 IRR with rechallenge. The incidence of IRR in the overall safety database (N = 485) was similar (18% versus 12%) between those who did (56%) and those who did not (44%) receive premedication. Monitor patients during and following LARTRUVO infusion for signs and symptoms of IRR in a setting with available resuscitation equipment. Immediately and permanently discontinue LARTRUVO for Grade 3 or 4 IRR.
Embryo-Fetal Toxicity
Based on animal data and its mechanism of action, LARTRUVO can cause fetal harm when administered to a pregnant woman. Animal knockout models link disruption of platelet-derived growth factor receptor alpha (PDGFR-α) signaling to adverse effects on embryo-fetal development. Administration of an anti-murine PDGFR-α antibody to pregnant mice during organogenesis caused malformations and skeletal variations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LARTRUVO and for 3 months after the last dose.
Most Common Adverse Reactions/Lab Abnormalities
The most commonly reported adverse reactions (all grades; grade 3-4) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were nausea (73% vs 52%; 2% vs 3%), fatigue (69% vs 69%; 9% vs 3%), musculoskeletal pain (64% vs 25%; 8% vs 2%), mucositis (53% vs 35%; 3% vs 5%), alopecia (52% vs 40%; 0% vs 0%), vomiting (45% vs 19%; 0% vs 0%), diarrhea (34% vs 23%; 3% vs 0%) decreased appetite (31% vs 20%; 2% vs 0%), abdominal pain (23% vs 14%; 3% vs 0%), neuropathy (22% vs 11%; 0% vs 0%), and headache (20% vs 9%; 0% vs 0%).
The most common laboratory abnormalities (all grades; grade 3-4) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were lymphopenia (77% vs 73%; 44% vs 37%), neutropenia (65% vs 63%; 48% vs 38%) and thrombocytopenia (63% vs 44%; 6% vs 11%), hyperglycemia (52% vs 28%; 2% vs 3%), elevated aPTT (33% vs 13%; 5% vs 0%), hypokalemia (21% vs 15%; 8% vs 3%), and hypophosphatemia (21% vs 7%; 5% vs 3%).
Use in Specific Populations
Lactation: Because of the potential risk for serious adverse reactions in breastfeeding infants, advise women not to breastfeed during treatment with LARTRUVO and for at least 3 months following the last dose.
For more information about LARTRUVO, please see full Prescribing Information at View Source
OR HCP ISI 19OCT2016
Actinium Announces Acceptance of Actimab-A Data for Poster Presentation at American Society of Hematology Annual Meeting
On October 19, 2016 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical Company developing innovative targeted payload immunotherapeutics for the treatment of advanced cancers, reported that data from the Company’s Actimab-A program, Actinium’s most advanced alpha particle immunotherapy program intended for newly diagnosed AML patients over the age of 60, has been selected by the American Society of Hematology (ASH) (Free ASH Whitepaper) Program Committee for poster presentation at the 58th Annual Meeting in San Diego, California on December 5, 2016 (Press release, Actinium Pharmaceuticals, OCT 19, 2016, View Source [SID1234515918]).
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Title: Phase I Trial of Targeted Alpha-Particle Therapy with Actinium-225 (225Ac)-Lintuzumab and Low-Dose Cytarabine (LDAC) in Patients Age 60 or Older with Untreated Acute Myeloid Leukemia (AML)
Abstract: #4050
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III
Location: San Diego Convention Center, Hall GH
Presentation: December 5, 6:00 PM – 8:00 PM
Abstracts are expected to be available at www.hematology.org on November 3, 2016 at 9:00 am Eastern time. In addition, the abstracts will be published online in the December 3, 2015 supplemental volume of Blood.
About Actimab-A
Actimab-A, Actinium’s most advanced alpha particle immunotherapy (APIT) program, is in a Phase 2 clinical trial for patients newly diagnosed with AML over the age of 60. Actimab-A is being developed as a first-line therapy and it has attracted support from some of the leading experts at the most prestigious cancer treatment hospitals due to the potential of its safety and efficacy profile. Actimab-A consists of the monoclonal antibody, HuM195, and the radioisotope, actinium-225. Actinium-225 decays by giving off high-energy alpha particles, which kill cancer cells. When actinium decays, it produces a series of daughter atoms, each of which gives off its own alpha particle, increasing the chances that the cancer cell will be destroyed. HuM195 is the humanized version of M195 and is a monoclonal antibody that targets CD33, which is abundantly found on myeloid leukemia cells. Both the alpha particle technology and HuM195 were initially developed at Memorial Sloan Kettering Cancer Center. Actimab-A is a second-generation therapy from the Company’s HuM195-Alpha program, which has now been studied in almost 90 patients in four clinical trials.