Oncology drugs for orphan indications: how are HTA processes evolving for this specific drug category?

Figures & data

Table 1 Drug case studies

Drug	Indicationa	Manufacturer	EMA MA date
Orphan oncology
Gazyvaro^®/obinutuzumab^Citation91	CLL: Gazyvaro^® in combination with chlorambucil is indicated for the treatment of adult patients with previously untreated CLL and with comorbidities making them unsuitable for full-dose fludarabine-based therapy	Roche Registration Ltd, Welwyn Garden City, UK	July 23, 2014
Imbruvica^®/ibrutinib^Citation92	CLL: Imbruvica^® is indicated for the treatment of adult patients with CLL who have received at least one prior therapy, or in first line in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemoimmunotherapy	Janssen-Cilag International N.V., Beerse, Belgium	October 21, 2014
Lynparza^®/olaparib^Citation93	Ovarian cancer: Lynparza^® is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy	AstraZeneca AB, Södertälje, Sweden	December 16, 2014
Cyramza^®/ramucirumab^Citation94	Gastric/gastro-esophageal cancer: Cyramza^® is a single agent or in combination with paclitaxel, it is indicated for the treatment of adult patients with advanced gastric cancer or gastro-esophageal junction adenocarcinoma with disease progression after prior platinum and fluoropyrimidine chemotherapy	Eli Lilly Nederland B.V, Utrecht, the Netherlands	December 19, 2014
Non-orphan oncology
Opdivo^®/nivolumab^Citation95	NSCLC: Opdivo^® is indicated for the treatment of locally advanced or metastatic squamous NSCLC after prior chemotherapy in adults	Bristol-Myers Squibb Pharma EEIG, Uxbridge, UK	June 19, 2015
Yervoy^®/ipilimumab^Citation96	Melanoma: Yervoy^® is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults	Bristol-Myers Squibb Pharma EEIG	July 13, 2011
Perjeta^®/pertuzumab^Citation97	Metastatic breast cancer: Perjeta^® is indicated for use in combination with trastuzumab and docetaxel in adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer, who have not received previous anti-HER2 therapy or chemotherapy for their metastatic disease	Roche Registration Limited	March 4, 2013
Zytiga^®/abiraterone^Citation98	Prostate cancer: Zytiga^® is indicated for the treatment of metastatic castration-resistant prostate cancer in adult men who are asymptomatic or mildly symptomatic, after failure of androgen deprivation therapy, in whom chemotherapy is not yet clinically indicated	Janssen-Cilag International N.V.	September 5, 2011

Note:

a Source: http://www.ema.europa.eu/.

Abbreviations: CLL, chronic lymphocytic leukemia; NSCLC, non-small cell lung cancer; EMA MA, European Medicines Agency Marketing Authorization.

Table 2 Country-specific processes for ODs

	Australia, PBAC	Canada, CADTH	England, NICE	France, HAS/CEPS/CT	Sweden, TLV
HTA criteria specific to ODs?	No Apart from LSDP, which requires drugs to meet strict criteria	Not nationally Five provinces have established processes for DRD reimbursement Ontario’s DRD evaluation framework is the best defined	No However, NICE HST section for appraising ultra-ODs; no explicit remit for ODs	No	No
HTA criteria specific to oncology?	No	HTA is carried out by the pCODR, which sits within the CADTH. The pCODR applies in all provinces except Quebec, which has separate advisory committee that focuses on cancer drugs (INESS)	No	No	No
Specific OD committee?	No	Not nationally	No However, the HST Evaluation Committee exists for ultra-ODs	No	No
Separate budget for ODs?	No There are potential options for OD funding through the LSDP for small number of very rare life-threatening conditions	No	No There is potential funding for oncology ODs through the CDF	No	No
Other notes	The “rule of rescue” may be applied as a supplement to OD submissions; however, the rule does not replace consideration of evidence-based comparative cost-effectiveness. There may be potential to gain access to oncology ODs and oncology drugs under the Highly Specialized Drugs program and the Efficient Funding of Chemotherapy program of Section 100 of National Health Act 1953	Canada is in the process of developing an OD regulatory framework Canadians have been able to access some ODs through Health Canada’s Special Access Programme	In 2014, NHS England published a statement of intent used to inform the development of a 5-year strategy for specialized services for patients with rare diseasesa	France has had a National Plan for Rare Diseases since 2005 with priorities including continuing efforts in favor of ODs	Sweden has greater flexibility in accepting higher ICERs depending upon the level of unmet need and disease severity

Note:

a NHS England. UK Strategy for Rare Diseases NHS England Statement of Intent (2014).⁹⁹

Abbreviations: CADTH, Canadian Agency for Drugs and Technologies in Health; CDF, Cancer Drugs Fund; CEPS, Comité Économique des Produits de Santé [Economic Committee for Health Products]; DRD, drugs for rare diseases; HAS, Haute Autorité de Santé [High Authority of Health]; HST, Highly Specialised Technology; HTA, health technology assessment; ICER, incremental cost-effectiveness ratio, INESS, Institut national d’excellence en santé et en services sociaux [National Institute of Excellence in Health and Social Services]; LSDP, Life Saving Drug Programme; NHS, National Health Service; NICE, National Institute for Health and Care Excellence; OD, orphan drug; PBAC, Pharmaceutical Benefits Advisory Committee; pCODR, pan-Canadian Oncology Drug Review; CT, Commission de la Transparence [Transparency Commission]; TLV, Tandvårds-och Läkemedelsförmånsverket [Dental and Pharmaceutical Benefits Agency].

Table 3 Comparative HTA decisions for orphan oncology drugs and non-orphan oncology drugs

		Orphan oncology drugs				Non-orphan oncology drugs
Drug indication		Gazyvaro^®/obinutuzumab CLL	Imbruvica^®/ibrutinib CLL	Lynparza^®/olaparib Ovarian cancer	Cyramza^®/ramucirumab Gastric/gastro-esophageal cancer	Opdivo^®/nivolumab NSCLC	Yervoy^®/ipilimumab Melanoma	Perjeta^®/pertuzumab Metastatic breast cancer	Zytiga^®/abiraterone Prostate cancer
Australia	ICERa	$45,000–$75,000	Deferredc	$45,000–$75,000	Not assessed	$45,000–$75,000	$45,000–$75,000	Deferredc	$45,000–$75,000
	Decision, Date	Negative, July 2014b	March 2016	Negative, July 2016		Negative, March 2016	Subject to risk-share agreement, November 2012b	March 2014	Negative, July 2014
Canada	ICERa	$29,868	$199,368	$197,368	$353,965	$62,673–$159,936	$269,299	Not reported	$128,197
	Decision, Date	Positive, January 2015	Conditional on improved CE, March 2015	Negative, September 2016	Conditional on improved CE, October 2015	Conditional on improved CE, June 2016	Conditional on improved CE, April 2012	Negative (invalid trial endpoint), July 2015	Conditional on improved CE, October 2013
England	ICERa	£20,000–£30,000	<£50,000	£49,826	£118,209	Guidance in development	£28,600–£47,900	£23,467–£42,955	£28,600–£32,800
	Decision, Date	Positive, with PASd, July 2015	Positive, with PASd, January 2017	Positive, with PASd,e, January 2016	Negative, January 2016		Positive, with PAS, July 2014	Positive, with PASd, December 2016	Positive, with PASd, April 2016
France	SMR	Important	Important	Important	Insufficient/moderate	Important	Moderate	Important	Important
	Decision, ASMR, Date	Positive, ASMR III, February 2015	Positive, ASMR III, June 2015	Positive, ASMR IV, June 2015	Negative, ASMR V, June 2015	Positive, ASMR III, February 2016	Negative, ASMR V, November 2014	Positive, ASMR III, July 2013	Positive, ASMR III, June 2015
Swedenf	ICERa	<290,000 SEK	830,000 SEK	964,000 SEK	1,450,000 SEK	1,070,000 SEK	1,080,000 SEK	2,600,000 SEK	<700,000 SEK
	Decision, Date	Positive, September 2014	Positive, June 2015	Positive, February 2015	Negative, October 2015	Positive, December 2016	Positive, March 2014	Positive, June 2013	Positive, subject to risk share agreement, June 2015

Notes:

a ICER per quality-adjusted life year gained.

b Reimbursed by PBAC under Section 100 (Efficient Funding of Chemotherapy).

c Drug has been assessed, but the decision regarding reimbursement recommendation deferred due to uncertainty in efficacy, safety, or CE analysis.

d Previously available through CDF.

e The drug cost of olaparib for people who remain on treatment after 15 months will be covered by the company.

f Swedish Council for Novel Therapeutics (NT Council).

Abbreviations: ASMR, Amélioration du Service Médical Rendu [improvement of medical benefit assessment]; CDF, Cancer Drugs Fund; CE, cost-effectiveness; CLL, chronic lymphocytic leukemia; HTA, health technology assessment; ICER, incremental cost-effectiveness ratio; NSCLC, non-small cell lung cancer; NT, novel therapeutics; PAS, patient access scheme; PBAC, Pharmaceutical Benefits Advisory Committee; SMR, Service Médical Rendu.

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