The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended six new-medicine approvals (including two orphan drugs). The CHMP additionally issued positive recommendations for the therapeutic-indication extension of seven medicines, including Opdivo (nivolumab) in renal-cell carcinoma.
IHS Life Sciences perspective | |
Implications | The February 2016 meeting of the CHMP issued six recommendations for new-medicine approvals in the European Union (EU), as well as seven recommendations for indication extensions. Among the positive recommendations are the orphan-designated medicines Alprolix (eftrenonacog alfa; Biogen, US) and Idelvion (albutrepenonacog alfa; CSL Behring, Germany) for the prevention and treatment of bleeding in haemophilia B patients. |
Outlook | Final market authorisation is expected to be issued by the European Commission within the next two months (the second quarter of 2016). Market authorisation by the European Commission will enable the commercialisation of medicines in all EU member states, as well as European Economic Area (EEA) countries Iceland, Liechtenstein, and Norway. |
The European Medicines Agency (EMA)'s Committee for Medicinal Products for Human Use (CHMP) published recommendations for the approval of six new medicines on 26 February 2016. Additionally, the CHMP issued seven recommendations for indication extensions. (The full text is available to view here.)
EMA: positive recommendation for new-medicine approvals | ||
Drug | Company | Indication |
Alprolix (eftrenonacog alfa) | Biogen (US) | Treatment and prophylaxis of bleeding in patients (all age groups) with congenital factor IX deficiency |
Idelvion | CSL Behring GmbH (Germany) | Treatment and prophylaxis of bleeding in patients (all age groups) with congenital factor IX deficiency |
Descovy (emtricitabine / tenofovir alafenamide) | Gilead Sciences (US) | Indicated in combination with other anti-retroviral agents for the treatment of patients (aged 12 and older) infected with HIV-1 |
Lonsurf (trifluridine / tipiracil) | Servier (France) | Treatment of adult patients with metastatic colorectal cancer, previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents |
Taltz (ixekizumab) | Eli Lilly (US) | Treatment of moderate to severe plague psoriasis in adult patients |
Palonosetron Hospira | Hospira (US) | Prevention of nausea and vomiting in adult patients undergoing cancer chemotherapy |
EMA: positive endorsement for new therapeutic indications | ||
Drug | Company | Changes to indication |
Opdivo (nivolumab) | Bristol-Myers Squibb (BMS, US) | Monotherapy for treatment of advanced renal-cell carcinoma after prior therapy in adults |
Giotrif (afatinib) | Boehringer Ingelheim (Germany) | Monotherapy indicated for the treatment of locally-advanced or metastatic NSCLC of squamous histology progressing on or after platinum-based chemotherapy |
Humira (adalimumab) | AbbVie (US) | Treatment of moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy |
Ruconest (conestat alfa) | Pharming Group (Netherlands) | Treatment of acute angioedema attacks in adults and adolescents with hereditary angioedema due to C1 esterase inhibitor deficiency |
TachoSil (human thrombin / human fibrinogen) | Takeda (Japan) | Indicated in adults for supportive sealing of the dura mater to prevent postoperative cerebrospinal leakage following neurological surgery |
Zydelig (idelalisib) | Gilead Sciences (US) | Indicated in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) |
Telzir (fosamprenavir) | ViiV Healthcare (UK) | Co-administration of paritaprevir and fosamprenavir/ritonavir is contraindicated due to lack of clinical data |
Source: European Medicines Agency | ||
Recommendation for Opdivo in the treatment of renal-cell carcinoma (RCC)
Among the highlights of the CHMP recommendations were two label extensions for BMS's Opdivo in treating advanced kidney cancer. In addition to existing uses (including NSCLC and advanced melanoma), the EMA supported a recommendation for the PD-1 inhibitor in adult patients with advanced RCC who have received prior therapy. The recommendation was based on a Phase III clinical trial (CheckMate 025) – involving 821 patients with RCC – assessing Opdivo against the cancer-treatment drug Afinitor (everolimus). The late-stage trial demonstrated that Opdivo had a median survival rate of 25 months, compared with 19.6 months in patients treated with Afinitor. Furthermore, the EMA accepted submissions showing that 22% of patients receiving Opdivo had a complete or partial shrinkage of their tumours against a rate of 4% for those patients administered with Afinitor. The CHMP's recommendation for Opdivo in treating RCC is the latest in a series of new approvals which BMS has gained for the breakthrough immune-oncology treatment. 2015 fourth-quarter global sales of Opdivo reached USD475 million, and the latest indication expansion should help to ensure that the drug's buoyant sales performance in Europe continues. Boosted by the addition of new indications, Opdivo is set to continue driving BMS's growth in 2016.
Outlook and implications
The European Commission is expected to publish staggered decisions granting final market approvals within two months of the publication of the CHMP opinion. The decision will be applicable to all 28 EU countries, in addition to Norway, Iceland, and Lichtenstein. Among the most notable recommendations are the orphan-designated medicines Alprolix and Idelvion. Once granted regulatory clearance by the European Commission, these products will benefit from a period of 10-year market exclusivity in Europe under orphan-medicine provisions. Under the terms of a collaboration agreement between Sobi (Sweden) and Biogen, Sobi holds exclusive rights over the final development, commercialisation, and manufacturing of Alprolix for the EU and Russian markets, as well as certain Middle Eastern and North African countries. The orphan-designated drug has already been approved for the treatment of haemophilia B patients in the United States, Japan, Australia, and Canada, where Biogen has the lead in development and manufacturing rights. On that basis, Biogen generated revenues of USD71 million (an increase of 77.5% year on year) in the latest fourth-quarter results. The treatment's strongest competition in 2016 continues to come from Baxter (US)'s bi-weekly haemophilia B drug Rixubis (recombinant coagulation factor IX), Pfizer (US)'s BeneFix (recombinant coagulation factor IX), and additionally Behring's Idelvion. Nevertheless, Sobi anticipates strong sales of Alprolix in Europe, and has updated its revenue forecast for 2016 to reflect this. In a statement issued on 29 February, the Swedish firm indicated that it expected to generate full-year revenues of SEK48–5 billion (USD561 million) in 2016. Of this, Alprolix is forecast to account for SEK300–325 million.
A further significant recommendation of note is Gilead Sciences' investigational fixed-dose combination for the treatment of HIV-1 infection in adult and adolescent patients with a body weight of at least 35 kg: Descovy (emtricitabine / tenofovir alafenamide) was approved at two dosage levels – 200/10 mg and 200/25 mg. The dosage regime is significantly smaller than Gilead's Viread (tenofovir disoproxil fumarate) and – according to the EMA – is associated with a "low impact on renal safety and bone mineral density" compared with Viread, but is deemed to have similar levels of efficiency. In February, Gilead reported the results of a Phase III study (Study 1089) evaluating the safety and efficacy of switching virologically-suppressed HIV-1-infected adult patients from Descovy to the newer Truvada (emtricitabine 200 mg + tenofovir 300 mg; Gilead, US) regimen. In the randomised, double-blind trial involving 663 patients, Descovy demonstrated similar virologic suppression rates, but improved renal and bone-density outcomes after 48 weeks. Gilead has confirmed that it is set to receive a US FDA decision on an application for Descovy in April.
Looking ahead, the CHMP announced that a final document on a new support mechanism for the fast-tracked development of new medicines addressing unmet medical needs (PRIME) was likely to be published on the agency's website in March 2016 (see Europe: 28 October 2015: European Commission publishes draft proposals on safe and timely access to new medicines). PRIME will establish a new early-stage innovative-medicines designation, modelled on the US FDA's breakthrough-status scheme. The draft proposals envisage two possible entry points to the PRIME scheme. Candidate products will be eligible to access PRIME at the proof-of-concept stage of drug development, with an additional possibility of gaining entry at the proof-of-principle stage (prior to Phase II trials).