FDA approves Roche’s Kadcyla (trastuzumab emtansine) for adjuvant treatment of people with HER2-positive early breast cancer.

Monday, the FDA approved Kadcyla for adjuvant treatment of HER-2 positive, early breast cancer patients who didn’t fully respond to drug therapy before surgery. With this approval, Kadcyla perhaps help Roche’s longtime breast cancer blockbuster Herceptin which is getting ready to face biosimilar competition later this year.

    FDA approves Roche’s Kadcyla for adjuvant treatment of people with HER2-positive early breast cancer with residual invasive disease after neoadjuvant treatment

        The approval is based on data showing Kadcyla cut the risk of disease recurring by half compared to Herceptin in the adjuvant setting for specific patients with HER2-positive early breast cancer
        The application was approved in just over 12 weeks under the US FDA’s Real-Time Oncology Review pilot programme

    Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the US Food and Drug Administration (FDA) has approved Kadcyla® (trastuzumab emtansine) for adjuvant (after surgery) treatment of people with HER2-positive early breast cancer (eBC) who have residual invasive disease after neoadjuvant (before surgery) taxane and Herceptin® (trastuzumab)-based treatment.

    “This approval is a significant treatment advance for HER2-positive early breast cancer. By working closely with the FDA and participating in the Real-Time Oncology Review pilot programme, we are able to make Kadcyla available for people with residual invasive disease after neoadjuvant therapy much sooner than anticipated,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “With every step forward in reducing the risk of disease recurrence, we come closer to the goal of helping each person with early breast cancer have the greatest opportunity for cure.”

    The goal in treating eBC is to provide people with the best chance for a cure, which may involve treatment before and after surgery as part of a comprehensive treatment approach.1,2 While we come closer to this goal with each advance, many people still have a disease recurrence in the long-term.3 Neoadjuvant treatment is given before surgery with the goal of shrinking tumours and helping to improve surgical outcomes.2 Adjuvant treatment is given after surgery and aims to eliminate any remaining cancer cells in the body to help reduce the risk of the cancer returning.2

    The FDA rapidly reviewed and approved the application under the FDA’s Real-Time Oncology Review (RTOR) and Assessment Aid pilot programmes, leading to an approval in just over 12 weeks after completing the submission. Kadcyla is the first Roche medicine approved under the RTOR pilot programme, which is exploring a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.4 For this indication, Kadcyla was also granted Breakthrough Therapy Designation, which is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases.5

    This approval is based on results of the phase III KATHERINE study showing Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival; iDFS) by 50% (HR=0.50, 95% CI 0.39-0.64, p6

 At three years, 88.3% of people treated with Kadcyla did not have their breast cancer return compared to 77.0% treated with Herceptin, an absolute improvement of 11.3%.6 People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease.7,8

The most common Grade 3 or higher side effects (>2%) with Kadcyla in the KATHERINE study were decreased platelet count and high blood pressure. The most common side effects (>25%) with Kadcyla were fatigue; nausea; increased blood levels of liver enzymes; musculoskeletal pain; bleeding; decreased platelet count; headache; numbness, tingling or pain in the hands or feet; and joint pain.6,9
About the KATHERINE study10

KATHERINE is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive eBC who have pathological invasive residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy that included Herceptin and taxane-based chemotherapy. The primary endpoint of the study is iDFS, which in this study is defined as the time from randomisation free from invasive breast cancer recurrence or death from any cause. Secondary endpoints include iDFS including second primary non-breast cancer, disease-free survival and overall survival.

 About Kadcyla

Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells, potentially limiting damage to healthy tissues.11,12 It combines two anti-cancer properties joined together by a stable linker: the HER2-targeting properties of trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1.13 Kadcyla is the only ADC approved as a single agent in 104 countries including the US and EU for the treatment of people with HER2-positive metastatic breast cancer who have previously received Herceptin and taxane chemotherapy, separately or in combination. Roche licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.
About Roche’s medicines for HER2-positive breast cancer

Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and advanced HER2-positive disease. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients.14Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta® (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test, which identifies people who will likely benefit from these medicines at the onset of their disease.
About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.
Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the tenth consecutive year, Roche has been recognised as the most sustainable company in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2018 employed about 94,000 people worldwide. In 2018, Roche invested CHF 11 billion in R&D and posted sales of CHF 56.8 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References

    Scharl A, et al. Geburtshilfe Frauenheilkd. 2015;75(7):683-91.
    Johns Hopkins Medicine. Neoadjuvant and Adjuvant Chemotherapy. [Internet; cited April 2019]. Available from: http://www.hopkinsmedicine.org/breast_center/treatments_services/medical_oncology/neoadjuvant_adjuvant_chemotherapy.html.
    Slamon D, et al. BCIRG 006 trial. Presented at: SABCS; 2015 Dec 6-10; San Antonio, TX, USA. Abstract #S5-04.
    US Food and Drug Administration. Real-Time Oncology Review Pilot Program. [Internet; cited April 2019]. Available from: https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/OCE/ucm612927.htm.
    US Food and Drug Administration. Breakthrough Therapy. [Internet; cited April 2019]. Available from: https://www.fda.gov/ForPatients/Approvals/Fast/ucm405397.htm.
    Minckwitz G, et al. N Engl J Med. 2018;DOI:10.1056/NEJMoa1814017.
    Cortazar P, et al. Lancet. 2014;384(9938):164-72.
    Gianni L, et al. Lancet. 2016;17(6):791-800.
    US Food and Drug Administration. Prescribing Information for Kadcyla. [Internet; cited April 2019]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125427lbl.pdf
    ClinicalTrials.gov. A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE). [Internet; cited April 2019]. Available from: https://clinicaltrials.gov/ct2/show/NCT01772472.
    Hurvitz SA, et al. J Clin Oncol. 2013;31(9):1157-63.
    Verma S, et al. N Engl J Med. 2012;367(19):1783-91.
    Junttila TT, et al. Breast Cancer Res Treat. 2011;128:347–56.
    Wolff AC, et al. J Clin Oncol. 2013;31(31):3997-4013.

Roche Will Acquire Anadys For $230 Million.

Roche (SIX: RO, ROG; OTCQX: RHHBY) and Anadys Pharmaceuticals, Inc. (NASDAQ: ANDS) today announced that the two companies have entered into a definitive merger agreement for Roche to fully acquire Anadys at a price of USD 3.70 per share in an all-cash transaction. This corresponds to a total cash consideration of approximately USD 230 million.

Based in San-Diego, California, USA, Anadys develops oral, small molecule therapeutics for the potential treatment of hepatitis C virus (HCV) infection. Setrobuvir (ANA598), Anadys’most advanced drug candidate, is a direct-acting antiviral compound that is currently being evaluated by Anadys in a phase II study in combination with Roche’s pegylated interferon (Pegasys) and ribavirin (Copegus).

• Jean-Jacques Garaud, Global Head of Roche Pharma Research and Early Development, said: “This acquisition augments our already strong HCV portfolio. Our aim is to offer physicians and hepatitis patients a powerful combination of therapies that bring us closer to a cure, even without the use of interferon. Anadys’ compounds provide additional modes of action that could lead to interferon-free treatment regimens without viral resistance.”
• Steve Worland, President and Chief Executive Officer of Anadys, said: “Since Anadys was founded, our focus has been on driving forward research that would make a real difference to the lives of patients, especially those with hepatitis. With Roche’s considerable capabilities and experience in HCV, this acquisition provides the best chance of success for the new potential treatments our team has been dedicated to developing.”

In addition to its lead programme with ANA598, Anadys is developing ANA773, an oral, small-molecule inducer of innate immunity in Phase I trials that may prove useful for treating HCV as well as other chronic infections and cancer.

Terms of the agreement

Under the terms of the merger agreement, Roche will promptly commence a tender offer to acquire all of the outstanding shares of Anadys’ common stock at a price of USD 3.70 per share in cash. This price represents a 256% premium to the closing price on 14 October 2011. The closing of the tender offer will be subject to the tender of a number of shares that, together with the shares owned by Roche, represent a majority of the total number of outstanding shares (assuming the exercise of all vested and unvested options and warrants having an exercise price per share less than the tender offer price) and other customary conditions. In addition, the transaction is subject to the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. The closing of the tender offer is expected to take place still in 2011.

Following completion of the tender offer, Roche will acquire all remaining shares through a second step merger. Directors and officers beneficially owning approximately 7.9% of the shares have agreed to tender their shares and otherwise support the transaction.

Citigroup Global Markets Inc is acting as financial advisor to Roche and Davis Polk & Wardwell LLP is acting as legal counsel. Lazard Ltd is acting as financial advisor to Anadys.

About setrobuvir (ANA598)

Setrobuvir is an investigational, orally administered, direct-acting antiviral (DAA) currently being evaluated for the treatment of chronic hepatitis C (HCV) infection. Specifically, it is a non-nucleoside polymerase inhibitor, and is currently in Phase IIb trials in combination with the current standard of care, Pegasys and Copegus. In clinical trials to date, setrobuvir has shown potent antiviral activity with a good safety profile. Roche plans to explore its use in combination with other direct acting antivirals already within its portfolio, with and without interferon.

Schizophrenia (RG1678), Multiple Sclerosis (Ocrelizumab) Drugs By Roche Enter Phase III Of Clinical Trials.I

Roche Holding AG (ROG.VX) Thursday announced that drugs slated to treat diseases like schizophrenia, and multiple sclerosis will enter phase III of clinical trails and may submit applications for as many as 10 new drugs by the end of 2013. Roche is the world's biggest cancer drug maker and is seeking new paths outside the oncology arena to mitigate the effects of recent development setbacks. Avastin, the company’s top seller, failed in studies in prostate, stomach and early colorectal cancer.

Start of phase III programs for potential breakthrough therapies in schizophrenia and multiple sclerosis

Schizophrenia

Positive phase II proof-of-concept data with RG1678 in patients with predominantly negative symptoms of schizophrenia were recently presented at an international medical meeting³. Based on these promising results, a global phase III program has been initiated which includes a total of six studies investigating RG1678 in combination with standard of care antipsychotic drugs in patients with either negative symptoms⁴ or residual positive symptoms of schizophrenia⁵. Running the studies for both indications in parallel will allow a better understanding of the effect of RG1678 on a broad spectrum of symptoms and its value in the management of patients at different phases of their disease. The first patient was randomized into the phase III program in November 2010.

RG1678 is an investigational first-in-class glycine reuptake inhibitor that normalizes glutamate neurotransmission, thereby targeting an important pathway in the treatment of psychiatric disorders. By normalising glutamate neurotransmission in the brain, RG1678’s unique mode of action could also have valuable therapeutic applications in other psychiatric indications beyond schizophrenia.

Multiple sclerosis

Ocrelizumab, a humanized anti-CD20 antibody administered as a six-monthly infusion, demonstrated a highly significant reduction in disease activity as measured by brain lesions (96% for 2000mg and 89% for 600mg ocrelizumab dosing regimens) and relapse rate (73% for 2000mg and 80% for 600mg ocrelizumab at week 24) compared to placebo in a phase II study in relapsing-remitting multiple sclerosis (RRMS). The efficacy data, amongst the highest seen in a phase II RRMS study, were recently reported at the ECTRIMS conference. Based on these results, ocrelizumab will move into phase III studies in multiple sclerosis. Two studies will explore ocrelizumab’s efficacy in RRMS head-to-head versus interferon, the current standard of care, and one study will investigate the potential of ocrelizumab in patients with primary-progressive multiple sclerosis (PPMS).  Phase III studies for ocrelizumab will commence in the first quarter of 2011.

 Press Release by Roche

FDA Extends The Review Of Avastin For Breast Cancer By Another 3 Months.

Avastin, a cancer fighting drug is under examination and FDA has announced today that the review will be extended by another 90 days. The review is to decide if the drug should be used in treatment of breast Cancer. The expensive drug seem to have not worked very well on breast cancer patients.
Avastin was approved by FDA in 2008 for breast cancer patients based on a trial. As a condition of approval, Roche, parent company of Genentech was required to conduct follow-up studies to demonstrate further the benefits of adding Avastin to conventional chemotherapy.In July an FDA advisory committee recommended the FDA, to revoke the Avastin's approval for breast cancer.

If the FDA revokes the approval, it's believed insurance companies will stop paying for this drug, which could cost more than $8,000 a month. Only the very rich will be able to afford the treatment.