Products

Date: 2018-09-20

Type of information: Positive opinion for the granting of a Market Authorisation in the EU

Product name: Paclical®/Apealea®

Compound: paclitaxel

Therapeutic area: Cancer - Oncology

Action mechanism:

• taxane derivative. Paclical®/Apealea® is a water-soluble formulation of Oasmia's patented non-toxic XR-17 technology and paclitaxel, one of the most widely used anti-cancer substances which is included in the standard treatment of a variety of cancers such as lung cancer, breast cancer and ovarian cancer. Paclical® consists of a freeze-dried powder that is dissolved in conventional solution for infusion and it has orphan drug designation in the EU and the U.S. Oasmia has completed a Phase-III study with Paclical® for ovarian cancer, which included 790 patients. Submission for marketing authorization in Europe will take place later this fall and the U.S. submission is planned for next year, depending on the availability of overall survival data.

Company: Oasmia Pharmaceutical (Sweden)

Disease:

• epithelial ovarian cancer
• primary peritoneal cancer
• fallopian tube cancer

Latest news:

• • On September 20, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Apealea®, intended for the treatment of ovarian cancer. Apealea® will be available as a 60 mg powder for solution for infusion. Apealea® also affects non-cancer cells such as blood and nerve cells, which can cause side effects. The benefit with Apealea® is its ability to improve progression-free survival in combination with carboplatin. The most common side effects are neutropenia, gastrointestinal disorders, peripheral neuropathy, arthralgia/myalgia, and infusion site reactions. The full indication is: "Apealea® in combination with carboplatin is indicated for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer." It is proposed that Apealea® be prescribed by physicians experienced in the use of anticancer therapies.
• The CHMP recommendation is based on clinical trials including the pivotal study OAS 07OVA. This study showed that the risks of disease progression or death after Apealea treatment in combination with carboplatin are similar as after Cremophor EL (CrEL)-formulated paclitaxel in combination with carboplatin.Key efficacy results in the per protocol population from the pivotal randomized clinical trial OAS-07OVA

  	Progression-free survival (PFS) (N=644)		Overall survival (OS) (N=644)
  Hazard ratio, HR1 (95% CI)	0.86 (0.72-1.03)		0.95 (0.78-1.16)
  	Apealea2	CrEL-paclitaxel2	Apealea2	CrEL-paclitaxel2
  Median, months (95% CI)	10.3 (10.1-10.7)	10.1 (9.9-10.2)	25.7 (22.9-28.1)	24.8 (21.7-27.1)

  ¹A longer PFS or OS for Apealea compared to CrEL-formulated paclitaxel is indicated by a HR less than 1.0. ²In combination with carboplatin.
• The most frequently reported adverse reactions after Apealea treatment in combination with carboplatin (?10%) were neutropenia, anorexia, peripheral sensory neuropathy, neuropathy peripheral, diarrhea, nausea, vomiting, alopecia, arthralgia, myalgia, asthenia, fatigue and infusion site reaction.
• • On December 11, 2017, Oasmia Pharmaceutical announced that it has received marketing approval for Paclical® in Kazakhstan. The drug l will be sold through Hetero Group and is planned to be launched during the first half of 2018.  
• • On 19-21 April 2016, the European Medicines Agency announced that paclitaxel has been subject to a new European marketing authorisation application under the centralised procedure.
• • On February 8, 2016. Oasmia Pharmaceutical announced the submission of a marketing authorization application (MAA) to the European Medicines Agency (EMA) for its lead cancer product Apealea® (also known as Paclical). Apealea is a new formulation of paclitaxel in nanoparticular form based Oasmia's XR-17 technology. The indication sought for Apealea is treatment of epithelial ovarian cancer in combination with carboplatin.
• This marketing authorization application is based on results from a Phase III study with Apealea on epithelial ovarian cancer conducted in 16 countries. The primary objective of the Phase III clinical study, which consisted of an aggregate of 789 patients, was to show non-inferiority of Apealea (250 mg/m2) versus Taxol (175 mg/m2), both in combination with carboplatin. Tumour response and progression was assessed by external readers in a blinded fashion using computed tomography evaluated through RECIST (standardized response evaluation criteria in solid tumours). The product has been approved in the Russian Federation since April 2015 and successfully launched by Oasmia’s partner Pharmasyntez.
• • On October 30, 2015, Oasmia Pharmaceutical announced that it its distribution partner in Russia and the Commonwealth of Independent States, CIS, Pharmasyntez, has placed its second order for Paclical®, for an end user sale value of $7.5 million. The announcement comes on the heels of the first order to the Russia market for $1.5 million in end-user value, totaling an end-user sales value of over $9 million USD in commercial orders within one week.
• • On October 28, 2015, Oasmia Pharmaceutical announced that it its distribution partner, Pharmasyntez, has executed the first order of Paclical® (water-soluble formulation of paclitaxel), Oasmia’s lead cancer product. Paclical was approved in April, 2015 and shipped earlier for commercial sampling purposes. While this announcement will result in the first commercial sales shipment later this quarter, Oasmia expects additional sales announcements. The first order to the Russia market represents an end-user sales value of over $1.5 million. Pharmasyntez, the Company’s Russia-based distribution partner marketing the product in Russia as well as the other Commonwealth of Independent States  countries believes in significant sales growth in the near future for Paclical. According to the Lancet Oncology Commission, the overall risk of dying from cancer in Russia is about 60%, which is higher than the 40% in the United Kingdom and the 33% in the United States. This, coupled with the existing market for cytostatics in Russia that amounts to over $2 billion with an annual growth rate of 36%, creates a significant market opportunity for the Company.
• • On October 5, 2015, Oasmia Pharmaceutical announced that it has shipped Paclical® (paclitaxel) to Pharmasyntez, its distribution partner in Russia which is expected to commence sales efforts promptly. Paclical ®was approved in April 2015 by the Russian agency. Pharmasyntez, the Company’s Russia-based distribution partner, is expected to market the product in Russia, Ukraine and Georgia as well as the Commonwealth of Independent States (“CIS”) countries. The market for cytostatics in Russia amounts to 2.05 billion USD with an annual growth rate of 36% according to DSM, the Russian equivalent of IMS Health.
• • On April 20, 2015. Oasmia Pharmaceutical announced that Paclical® received market authorization in the Russian Federation by the Russian Ministry of Health. Paclical is the first water-soluble cancer drug with paclitaxel to receive a market authorization. Paclical is planned for launch in the second half of 2015. Paclical® was approved for treatment of epithelial ovarian cancer in combination with carboplatin. XR-17 is non-toxic and forms water soluble nanoparticles with paclitaxel. The Russia-based company Pharmasyntez holds the distribution rights to Paclical® in Russia and will be responsible for marketing the product in Russia and the CIS (Commonwealth of Independent States) countries. CIS consists of Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Tajikistan, Georgia, Uzbekistan, Ukraine and Turkmenistan. The market for cytostatics in Russia amounts to 2.05 billion with an annual growth rate of 36 % according to DSM, the Russian equivalent of IMS Health.
• The market authorization is based on results from the Phase III study with Paclical® on epithelial ovarian cancer conducted in 16 countries, but with approximately 45% of the patients being Russian, Paclical is already well-known by Russian oncologists. The primary objective of the Phase III clinical study, which consisted of an aggregate of 789 patients, was to show non-inferiority of Paclical (250 mg/m2) versus Taxol (175 mg/m2), both in combination with carboplatin. Tumour response and progression was assessed using a biomarker, CA 125, evaluated centrally according to GCIG-criteria, (Gynaecological Cancer Intergroup).

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:

UE authorization:

Favourable opinion UE: 2018-09-20

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

• • On October 28, 2015, Oasmia Pharmaceutical announced  that it its distribution partner, Pharmasyntez, has executed the first order of Paclical®, Oasmia’s lead cancer product. While this announcement will result in the first commercial sales shipment later this quarter, Oasmia expects additional sales announcements. The first order to the Russia market represents an end-user sales value of over $1.5 million.

Is general: Yes