No announcement yet.


This is a sticky topic.
  • Filter
  • Time
  • Show
Clear All
new posts

    Ocrevus Assessment Report European Medicines Agency November 2017

    I believe it is prudent to monitor closely for breast cancer since there were more cancer cases, and especially breast cancer, which showed up with Ocrevus during trials than with the two comparators which were Rebif and placebo.

    We should remember that in trials… RRMS Ocrevus (n-825, the number taking it) was compared to Rebif (n-826) and in PPMS (n-486) Ocrevus was compared to placebo (n-239).

    Quoting from page 140 (the italics are mine) … QUOTE “Malignancies
    RMS (relapsing MS) … the rate per 100PY (PY = patient years) of malignancy was 0.14 … for the IFN (Rebif) group and 0.28 for the OCR (ocrelizumab) group.”

    PPMS (Primary Progressive MS) The rate per 100PY of malignancy events was 0.30 … for the placebo group and 0.92 for the OCR group.” End Quote

    Quoting, from pages 149 and 150

    “At least 1173 MS patients have been exposed to the proposed dose 600 mg dose for more than 95 weeks. However, long-term exposure data do not allow conclusive evaluation of the risk of malignancies as well as rare risks, such as PML. The RMS and PPMS patient population included in the controlled MS trials is a selected patient population, not entirely representative of the MS patient population target of the two claimed indications.

    For instance median age of PPMS enrolled patients was 46 years...

    There is no information regarding patients older than 55 years. The absence of safety data in patients ≥55 years of age requires a more cautious approach with regard to the observed imbalance in malignancies, including breast cancer, observed in OCR-treated patients relative to comparator (IFN or placebo), as it is well known that the risk of malignancies increases with age.” End Quote

    I quote page 172 broken into paragraphs for readability …

    3.5 Uncertainties and limitations about unfavourable effects

    “More than 1173 MS patients were exposed to the proposed dose 600 mg dose for more than 95 weeks with a total of 4485 patient years of exposure to ocrelizumab in the MS population. However, even if this is a large safety database rare adverse events or adverse events likely to occur later might not have been captured. In particular, available long term exposure data do not allow to conclusively evaluate both the risk of malignancies as well as PML.

    Moreover, the exclusion of patients >55 years old, prevents the assessment of the safety profile of OCR in the elderly, in particular with respect to malignancies, the risk of which is known to increase with age.

    Patients with a history of recurrent or chronic infections or immunodeficiency, and patients with a history of ischemic cerebrovascular disorders were excluded from the pivotal trials.

    Cardiovascular disease was not among exclusion criteria, but there was only one enrolled patient with a history of cardiovascular disease (SMQ cardiac failure). The safety of OCR in the presence of the above mentioned morbidities is thus not assessable at present.

    Opportunistic infections, but not PML were seen in the RA population where ocrelizumab exposure corresponds to 7324 patients years albeit in dose levels ranging from 20 mg to 2000 mg. Opportunistic and serious infections was also seen in the SLE and LN population and 6% and 3%, respectively died in these population due to infections.

    It is uncertain if safety data from these patient populations can be extrapolated to the MS population as patients in the RA, SLE and LN population also received additional immunosuppressant treatment, had different comorbidities and the RA population was older than the MS population.

    It is thus unknown if prior or current immunosuppressant treatment in the MS population will increase the risk of infections. It is also unknown, had the safety database been as large as in RA, if cases of opportunistic infections would have occurred in the MS population.

    Up to the 30 Jun 2016, there were in total 26 cases of malignancies reported in MS patients treated with ocrelizumab. There was an imbalance in the incidence of malignancies in the ocrelizumab groups compared to IFN and placebo with a cluster of breast cancers in the ocrelizumab groups.

    There were no cases of breast cancer in the IFN or placebo groups whereas there were 3 cases in the RMS ocrelizumab group and 4 cases in the PPMS ocrelizumab group...

    In randomised controlled trials only about 20% of randomized RA patients received more than 2 OCR doses and only 38 patients received up to 8 OCR doses in the open label part.

    The higher incidence of malignancies, with a cluster for breast cancer, observed in OCR-treated patients relative to comparator (IFN or placebo) is a cause of concern, particularly as age >55 years was an exclusion criteria.

    Additionally, long-term safety has not been investigated, and for this reason the applicant will perform post-approval studies to address this issue.”

    Quoting page 176, “The safety profile of ocrelizumab shows an increased frequency of malignancies compared to control groups, which seem to be driven by a cluster of breast cancer. However, the incidence was not higher as compared to epidemiological data and available data do not allow to definitely establish - nor rule out - a clear causality to ocrelizumab treatment.” End Quotes.

    Only time and data can definitely establish if cancer is more of a risk with Ocrevus. Breast cancer appeared more frequently than other types in trials. Prudence dictates those taking Ocrevus should closely monitor for cancer, especially breast cancer.
    Last edited by Seasha; 07-16-2018, 11:35 PM. Reason: per request by poster