Products

Date: 2018-07-30

Type of information: Granting of a Market Authorisation in the EU

Product name: Aimovig®

Compound: erenumab

Therapeutic area: CNS diseases - Neurological diseases

Action mechanism:

• monoclonal antibody. AMG 334 is a fully human monoclonal antibody under investigation for the prevention of migraine. AMG 334 inhibits Calcitonin-Gene-Related-Peptide (CGRP) by targeting its receptor, rather than CGRP itself, which is believed to transmit signals that can cause incapacitating pain.
• In August 2015, Novartis entered into a global collaboration with Amgen to commercialize and develop new treatments in the field of Alzheimer's disease and migraine, including AMG 334 (currently in phase III studies for episodic migraine and a phase II study for chronic migraine) and AMG 301 (currently in a phase I study for migraine).
• Aimovig is the first and only treatment specifically designed for migraine prevention to be approved in the European Union, Switzerland, the US and Australia.

Company: Amgen (USA - CA) Novartis (Switzerland)

Disease: migraine

Latest news:

• • On July 30, 2018 - Novartis announced that the European Commission (EC) approved Aimovig™(erenumab) for the prevention of migraine in adults experiencing four or more migraine days per month. In the extensive clinical program of 2,600 patients, those on Aimovig™ experienced significant reductions in their number of migraine days per month, with a safety and tolerability profile similar to placebo[1]-[3]. Aimovig™ can be self-administered or administered by another trained person every four weeks with the SureClick® autoinjector pen, an established device commonly used for a range of different conditions.
• Aimovig™ showed efficacy even in a difficult-to-treat population. It is the only CGRP-R pathway therapy specifically studied in patients who had failed on two to four previous treatments commonly used for migraine prevention. Furthermore, in an interim analysis from a five year open label extension (OLE) in episodic migraine, it was demonstrated that more than one in four (26%), patients taking Aimovig 70 mg, who were still enrolled and assessed for migraine over month fifteen, were completely migraine free.
• A post-approval access program has been opened to provide Aimovig in countries where the local regulations allow provision of unapproved or yet to be reimbursed therapies. Support programs are also being developed for eligible patients in line with local regulations that include personalized services, information and resources to support them as they begin their treatment with Aimovig™.
• The EMA decision is applicable to all 28 European Union member states plus Iceland, Norway and Liechtenstein. Aimovig (erenumab-aooe) received U.S. FDA approval for the preventive treatment of migraine in adults on May 17, 2018. Aimovig received Swissmedic approval in Switzerland on July 13, 2018 and Australian TGA registration on July 3, 2018. Additional regulatory filings are underway with other health authorities worldwide.
• •  On July 3, 2018, the Institute for Clinical and Economic Review released a Final Evidence Report and Report-at-a-Glance on three calcitonin gene-related peptide (CGRP) inhibitors for prevention of migraine attacks: erenumab (Aimovig™, Amgen/Novartis), fremanezumab (Teva), and galcanezumab (Eli Lilly). Erenumab was approved in May of 2018, while the other two agents remain under FDA review. ICER's report was reviewed at a June 2018 public meeting of the California Technology Assessment Forum (CTAF). Panel members voted that evidence was adequate to demonstrate a net health benefit of the CGRP inhibitors for individuals with chronic migraine and no other available treatment options. While acknowledging the significant impact even infrequent migraine has on day-to-day life, a majority of Panel members pointed to the unknown long-term risks in voting that current evidence is inadequate to show a net health benefit of the CGRP inhibitors for individuals with episodic migraine. Panel members noted that the therapies may provide potential additional benefits beyond those studied in clinical trials, including reduced family/caregiver burden, a novel mechanism of action that may allow for successful treatment of patients without other options, and increased productivity. Further, the high severity and lifetime burden of illness, along with the significant uncertainty around long-term risks and the magnitude and durability of benefit, were noted as key contextual considerations that factored into CTAF's assessment of value.
• Voting on the long-term value for money of erenumab, the only CGRP drug with a publicly-available price, a majority of the panel voted that erenumab represents an intermediate value in adults with chronic migraine, and votes were split between intermediate and low long-term value for money when the drug is used for patients with episodic migraine.
• • On June 1, 2018, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended granting a marketing authorisation for Aimovig™ (erenumab), the first human monoclonal antibody therapy for prevention of migraine.  The benefits and safety of Aimovig™ were studied in two pivotal trials involving 667 patients with chronic migraine and 955 with episodic migraine. After three months of treatment, patients with chronic migraine showed a reduction of 2.5 monthly migraine days on average compared to placebo. For patients with episodic migraine the reduction was either 1.3 or 1.8 days, depending on the dose taken. The most common adverse events observed were injection site reactions, constipation, muscle spasms and pruritus.
• Aimovig™ should only be taken by patients who have at least 4 migraine days a month. It is a solution for injection that is administered once a month. Patients can inject themselves after appropriate training.
• • On May 31, 2018, the Institute for Clinical and Economic Review (ICER) released an Evidence Report assessing the comparative clinical effectiveness and value of three calcitonin gene-related peptide (CGRP) inhibitors for prevention of migraine attacks: erenumab (Aimovig™, Amgen/Novartis), fremanezumab (Teva), and galcanezumab (Eli Lilly). ICER's report found that the CGRP inhibitors prevented approximately one to three days of migraine per month, on average. Cost-effectiveness analyses for erenumab and fremanezumab, using an estimated annual net price of $5,000, found that the price of the therapies aligns with the value to patients for whom other preventive treatments have failed. The drugs were not found to be cost-effective, however, if used to treat patients who had not already tried existing preventive treatments, which are far less expensive.
• ICER's previously released Draft Evidence Report used a placeholder price of $8,500 per year; however, following the announcement of erenumab's list price of $6,900 annually, ICER updated these analyses. Assuming a 27% discount reflective of typical rebates and discounts to reach a net price of $5,000, cost-effectiveness findings became substantially more favorable than in the draft report.
• • On May 17, 2018, the FDA approved Aimovig™ (erenumab-aooe) for the preventive treatment of migraine in adults. The treatment is given by once-monthly self-injections. Aimovig™ is the first FDA-approved preventive migraine treatment in a new class of drugs that work by blocking the activity of calcitonin gene-related peptide, a molecule that is involved in migraine attacks.
• The effectiveness of Aimovig™ for the preventive treatment of migraine was evaluated in three clinical trials. The first study included 955 participants with a history of episodic migraine and compared Aimovig to placebo. Over the course of six months, Aimovig-treated patients experienced, on average, one to two fewer monthly migraine days than those on placebo. The second study included 577 patients with a history of episodic migraine and compared Aimovig to placebo. Over the course of three months, Aimovig-treated patients experienced, on average, one fewer migraine day per month than those on placebo. The third study evaluated 667 patients with a history of chronic migraine and compared Aimovig to placebo. In that study, over the course of three months, patients treated with Aimovig experienced, on average, 2 ½ fewer monthly migraine days than those receiving placebo. The most common side effects that patients in the clinical trials reported were injection site reactions and constipation.
• Aimovig™  is self-administered once monthly via Amgen's device, the SureClick® autoinjector, and does not require a loading dose. Some patients may benefit from a dosage of 140 mg once monthly.
• A dedicated Phase 3b study (LIBERTY) in difficult-to-treat populations - those with episodic migraine who have failed two to four prior treatments - showed that patients taking Aimovig had nearly three-fold higher odds of having their migraine days cut by half or more compared to placebo.The efficacy, tolerability and safety of Aimovig has been assessed in more than 3,000 patients, including LIBERTY and an ongoing open-label extension of up to five years in duration. In clinical studies of Aimovig, the most common adverse reactions were injection site reactions and constipation.
• The U.S. list price of Aimovig is $575 for once monthly 70 or 140 mg single-use prefilled SureClick® autoinjector(s), or $6,900 annually. While out-of-pocket costs will vary depending on insurance status, the Aimovig Copay Program may be able to help reduce a patient's out-of-pocket costs to as little as $5 per month for eligible patients with commercial insurance. Aimovig is expected to be available to patients within one week
• • On July 21, 2017, Amgen announced that the FDA has accepted for review the Biologics License Application (BLA) for Aimovig™ (erenumab) for the prevention of migraine in patients experiencing four or more migraine days per month. If approved, Aimovig is expected to be the first-and-only monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor, specifically designed for the prevention of migraine
• The BLA for Aimovig includes data from pivotal studies of more than 2,600 patients experiencing four or more days of migraine per month. Phase 2 and Phase 3 clinical studies of Aimovig versus placebo have demonstrated a reduction in the number of migraine-affected days, disability and acute medication use for patients with episodic and chronic migraine. The safety profile of Aimovig was similar to placebo across all treatment arms in the Phase 2 and Phase 3 studies for up to six months. The most common adverse events across the studies were upper respiratory tract infection, injection site pain, nausea and nasopharyngitis.
• The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of May 17, 2018.

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE:

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2018-05-17

UE authorization: 2018-07-30

Favourable opinion UE: 2018-06-01

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

• • On July 3, 2018, the Institute for Clinical and Economic Review released a Final Evidence Report and Report-at-a-Glance on three calcitonin gene-related peptide (CGRP) inhibitors for prevention of migraine attacks: erenumab (Aimovig™, Amgen/Novartis), fremanezumab (Teva), and galcanezumab (Eli Lilly). ICER's report was reviewed at a June 2018 public meeting of the California Technology Assessment Forum (CTAF). Panel members voted that evidence was adequate to demonstrate a net health benefit of the CGRP inhibitors for individuals with chronic migraine and no other available treatment options. While acknowledging the significant impact even infrequent migraine has on day-to-day life, a majority of Panel members pointed to the unknown long-term risks in voting that current evidence is inadequate to show a net health benefit of the CGRP inhibitors for individuals with episodic migraine.
• Panel members noted that the therapies may provide potential additional benefits beyond those studied in clinical trials, including reduced family/caregiver burden, a novel mechanism of action that may allow for successful treatment of patients without other options, and increased productivity. Further, the high severity and lifetime burden of illness, along with the significant uncertainty around long-term risks and the magnitude and durability of benefit, were noted as key contextual considerations that factored into CTAF's assessment of value.
• Voting on the long-term value for money of erenumab, the only CGRP drug with a publicly-available price, a majority of the panel voted that erenumab represents an intermediate value in adults with chronic migraine, and votes were split between intermediate and low long-term value for money when the drug is used for patients with episodic migraine.
• Following the voting session during the CTAF meeting, a policy roundtable of experts - including patient advocates, physicians, public and private payers, and drug manufacturers - convened to discuss the implications of the evidence for policy and practice. Key recommendations stemming from the roundtable discussion include:
• When responsible pricing is accomplished and the net price of CGRP inhibitors aligns with the estimated added benefit for patients, prior authorization criteria should be relatively streamlined and allow documentation of eligibility through a clinician statement that patients have attempted adequate trials of two to three other preventive therapies rather than requiring extensive submission of clinical documents.
• Following the example set by the launch of the first CGRP inhibitor, manufacturers should continue to exercise restraint and ensure net prices align reasonably with the added benefits for patients. Consideration of price increases in future years should be transparently justified by new clinical evidence of superior performance.Clinicians should be aware of the uncertainties in long-term efficacy and potential harms when prescribing CGRP inhibitors. The FDA has requested additional research into liver toxicity and risks for heart attack and stroke after exposure to erenumab, and into potential adverse effects when erenumab is used during pregnancy.

Is general: Yes