The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has issued 10 positive recommendations for marketing authorisations, including three orphan medicines, as well as recommended the extension of therapeutic indications for four previously authorised drugs.
IHS Life Sciences perspective | |
Significance | The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency issued positive opinions on 10 new drugs for marketing approval in the European Union during a meeting on 16–18 June. This brings the total recommend marketing approvals to 44 in 2015. In addition, the committee recommended extensions to therapeutic indications on four products already authorised for commercialisation in the EU. The CHMP provided a negative opinion on one drug. |
Implications | Among the positive opinions issued was for Swiss firm Novartis's oral drug Odomzo (sonidegib) for the treatment of basal cell carcinoma. In addition, the CHMP recommended extending the therapeutic indication of Swiss Roche's Perjeta (pertuzumab) targeting HER2-positive early stage breast cancer. |
Outlook | The favourable opinions have been submitted to the European Commission for final approval. A positive decision by the European Commission will enable the commercialisation of the drugs in all EU member states, as well as Iceland, Liechtenstein, and Norway. In most cases, a final decision by the European Commission is likely to be publicised in the third quarter. |
The European Medicines Agency (EMA)'s Committee for Medicinal Products for Human Use (CHMP) during its meeting on 16–18 June issued 10 positive opinions for new drug approvals, comprising six originators and four generics. The agency also issued approval of six indication extensions. The full text is available here.
Positive CHMP recommendation on new medicines (non-orphan medicines) | ||||
Drug | Company | Indicators | Benefits | Dosage |
Odomzo (sonidegib) | Novartis (Switzerland) | Adult patients with locally advanced basal cell carcinoma who are not amendable to curative surgery or radiation therapy. | Reduces locally advanced basal cell carcinoma with a response rate of 54% and a progression-free survival of 22 months. | 200 mg hard capsules |
Respreeza (human alpha 1-proteinase inhibitor) | CSL Behring (Australia) | Maintenance treatment, to slow the progression of emphysema in adults with documented severe alpha 1-proteinase inhibitor deficiency. | Reduction of 34% in annual rate of lung density decline over two-year period. | 1000 mg powder and solvent for solution for infusion |
Positive CHMP recommendation on new medicines (orphan drug designation) | ||||
Drug | Company | Indicators | Benefits | Dosage |
Kanuma (sebelipase alfa) | Synageva (acquired for USD8.4 billion in May by Alexion, US) | Long-term enzyme replacement therapy in patients of all ages with lysosomal acid lipase deficiency. | Chronic liver disease, metabolic disorders, and Wolman disease beyond 12 months. | 2 mg / ml concentrate for solution for infusion |
Strensiq (asfotase alfa) | Alexion (US) | Long-term enzyme replacement therapy in patients with paediatric-onset hypophosphatasia. | Promotes mineralisation of the skeleton. | 40 mg/ml and 100 mg/ml solutions for injection |
Farydak (panobinostat) | Novartis (Switzerland) | Adult patients with relapsed or refractory multiple myelomas who have received at least two previous regimens, including Velcade (bortezomib; Takeda, Japan & Janssen, US) and an immunomodulatory agent. | First in class histone deacetylase inhibitor to be effective in multiple myeloma. | 10, 15, 20 mg |
Raxone (idebenone) | Santhera (Germany) | Treatment of visual impairment in adolescent and adult patients with Leber's Hereditary Optic Neuropathy (LHON). | Raxone will be the first treatment option for LHON. | 150 mg film coated tablets |
Positive CHMP recommendation on generic medicines | ||||
Drug | Company | Indicators | Generic version | Dosage |
Docetaxel | Hospira (UK) | Adjunctive treatment of operable node-positive breast cancer and operable node-negative breast cancer (in combination with doxorubicin and cyclophosphamide). Locally advanced or metastatic cancer after failure of cytotoxic therapy (in combination with tratuzumab). Locally advanced or metastatic breast cancer after failure of chemotherapy (in combination with capecitabine). Unresectable locally advanced or metastatic non-small lung cancer in patients who have not previously received chemotherapy (in combination with cisplatin) Hormone refractory metastatic prostate cancer (in combination with prednisone or prednisolone). Metastatic gastric adenocarcinoma who have not received prior chemotherapy for metastatic disease (in combination with cisplatin and 5-fluorouracil). Locally advanced squamous cell carcinoma of the head and neck (in combination with cisplatin and 5-fluorouracil). | Generic of Taxotere (docetaxel; Sanofi, France) | 20 mg/ml concentrate for solution for infusion |
Aripiprazole Sandoz (aripiprazole) | Sandoz (generic unit of Novartis, Switzerland) | Schizophrenia in adults and in adolescents aged 15 years and over. Moderate to severe manic episodes in bipolar 1 disorder and for the prevention of new manic episodes in adults. | Generic of Abilify (aripiprazole; BMS, US and Otsuka, Japan) | 5, 10, 15, 20, 30 mg tablets |
Duloxetine Zentiva (duloxetine) | Zentiva (generics division of Sanofi, France) | Major depressive disorder and diabetic peripheral neuropathic pain. | Generic of Cymbalta (duloxetine; Eli Lilly, US) | 30 mg and 60 mg gastro-resistant capsules |
Pregabalin Accord (pregabalin) | Accord (UK) | Adjunctive therapy in adults with partial seizures with or without secondary generalisation. Also indicated for the treatment of generalised anxiety disorder in adults | Generic of Lyrica (pregabalin; Pfizer, US) | 25, 50, 75, 100, 150, 200, 225, 300 mg hard capsules |
Negative CHMP opinion on new medicines | ||||
Drug | Company | Indicators | ||
Heparesc (human heterologous liver cells) | Cytonet | Intended for the treatment of children from birth to 3 years of age with rare urea cycle disorders. | ||
Positive CHMP recommendation on extending therapeutic indications | ||||
Drug name | Company | New indication | ||
Humira (adalimumab) | AbbVie (US) | Active moderate to severe hidradentis supprativa (acne inversa) in adult patients with an inadequate response to convention systemic hidradentis supprativa therapy. | ||
Perjeta (pertuzumab) | Roche (Switzerland) | Neoadjuvant treatment of adult patients with HER2-positive, locally advanced inflammatory, or early stage breast cancer at high risk of recurrence (in combination with tratuzumab or chemotherapy). | ||
Voncento (human coagulation factor VIII, human von Willebrand factor) | CSL Behring (Germany) | Prophylaxis and treatment of haemorrhage or surgical bleeding in patients with von Willebrand disease (VWD), when desmopressin (DDAVP) treatment alone is ineffective or contraindicated. | ||
Levemir (insulin detemir) | Novo Nordisk (Denmark) | For treatment of diabetes mellitus in adults, adolescents and children aged 1 year and above. | ||
Roche secures expanded indications for Perjeta, one of its best-selling drugs
The CHMP recommendation expands the therapeutic indications for Roche's Perjeta (pertuzumab). The new indication applies for use before surgery on HER2-positive early breast cancer (eBC) in combination with Herceptin (tratuzumab) and docetaxel chemotherapy. Data from the NeoSphere Phase II research – involving a randomised multi-centre trial enrolling 417 people with newly diagnosed HER2-positive, operable, locally advanced, or inflammatory eBC, the primary endpoint of which was pathological complete response (pCR) – showed that 40% of patients treated with a Perjeta/Herceptin combination had no detected tumour tissue in the affected breast and local lymph nodes at the time of eBC surgery. This compared with 21.5% of patients receiving Herceptin and chemotherapy alone. A Phase III trial on the post-surgery role of the Perjeta-regimen in treating HER2-positive eBC is ongoing. The NeoSphere results demonstrated that patients receiving Perjeta are 31% less likely to experience disease deterioration, relapse or death after three years, compared with Herceptin and chemotherapy. Perjeta has already been approved in the United States and 20 other countries as a neoadjuvant therapy in HER2-positive eBC. Product sales of Perjeta reached USD343 million (of which USD95 million were European sales) for the first quarter of 2015, and the company is likely to be boosted by an uptake of a Perjeta-Herceptin combination in the 28 EU member states, including Norway, Iceland, and Liechtenstein.
Novartis's Farydak receives further boost on the back of a positive EMA recommendation
The EMA issued a positive opinion on Novartis's Farydak (panobinostat) capsules in combination with bortezomib and dexamethasone for the treatment of patients with multiple myeloma. The approval was based on data from the Phase III PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) study, where the addition of panobinostat was shown to increase progression-free survival by 7.8 months. This is further positive news for the Swiss company, which secured regulatory approval in the US in February. Assuming the European Commission authorises the market entry of Farydak in 2015, the Novartis drug will face head-to-head competition from Kyprolis (carfilzomib; Amgen, US) and Pomalyst (pomalidomide; Celgene, US), which reached global sales of USD679.7 million in 2014.
EMA to undertake review on Duchenne muscular dystrophy (DMD) treatment
Elsewhere, the EMA said that it had accepted a marketing authorisation application to review the US-based company BioMarin's DMD treatment drisapersen (see Netherlands - Europe: 10 June 2015: BioMarin submits EU market authorisation application for muscular dystrophy drug drisapersen). A request to review a marketing authorisation application for the haemophilia B treatment Alprolix (long-acting coagulation factor IX [recombinant], Fc fusion protein) was also accepted (see Sweden - Europe: 5 June 2015: Sobi and Biogen submit market authorisation application for haemophilia drug Alprolix).
Outlook and implications
The European Commission is expected to align very closely with the CHMP's recommendations, and in the vast majority of cases final product approval is regarded as a formality. A European Commission decision is typically expected within two months, which should enable the companies affected to commercialise their products, within the European Economic Area, in the latter half of 2015.
Among the orphan-designated medicines that have been recommended for marketing authorisation, regulatory approval of two enzyme replacement therapies for rare genetic life-threatening diseases are the most significant. However, it is noteworthy that Strensiq has been conditionally cleared under 'exceptional circumstances' owing to insufficient amounts of safety and efficacy data to meet the EMA requirements. As a consequence, the CHMP has requested further clinical data should be collected. The probable marketing authorisation for the orphan medicine Kanuma would also have a positive impact, as there is currently no approved therapy for the lysosomal acid lipase deficiency condition.
Assuming that the European Commission subsequently ratifies the positive opinions of the CHMP, as is highly likely, Novartis's Odomzo treatment for basal cell carcinoma should begin being rolled out in Europe in 2015. This will allow the Swiss company to further expand its oncology business, which represents a major driver for revenues. The company has also filed for approval in Switzerland and Australia, and made an application for US FDA approval in the third quarter of 2014. In competition terms, Odomzo will be up against Erivedge (vismodegib; Roche, Switzerland), which has received market approval in the EU in July 2013 as a treatment option for patients with advanced basal cell carcinoma. Total annual sales of Erivedge were USD128.8 million in 2014 (USD39 million in EU markets). However, high-discontinuation rates with vismodegib have been associated with the treatment.