Federal Register / Vol. 86, No. 110 / Thursday, June 10, 2021 / Notices 30945 

1 Kluetz, P.G., A. Slagle, E.J. Papadopoulos, et al., 

2016, ‘‘Focusing on Core Patient-Reported 

Outcomes in Cancer Clinical Trials: Symptomatic 

Adverse Events, Physical Function, and DiseaseRelated Symptoms,’’ Clinical Cancer Research, 

22(7):1553–1558. 

both copies to the Dockets Management 

Staff. If you do not wish your name and 

contact information to be made publicly 

available, you can provide this 

information on the cover sheet and not 

in the body of your comments and you 

must identify this information as 

‘‘confidential.’’ Any information marked 

as ‘‘confidential’’ will not be disclosed 

except in accordance with 21 CFR 10.20 

and other applicable disclosure law. For 

more information about FDA’s posting 

of comments to public dockets, see 80 

FR 56469, September 18, 2015, or access 

the information at: https://

www.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, go to https://

www.regulations.gov and insert the 

docket number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Dockets Management 

Staff, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

Submit written requests for single 

copies of the draft guidance to the 

Division of Drug Information, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10001 New 

Hampshire Ave., Hillandale Building, 

4th Floor, Silver Spring, MD 20993– 

0002, or to the Office of 

Communication, Outreach and 

Development, Center for Biologics 

Evaluation and Research (CBER), Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 3128, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

requests. The draft guidance may also be 

obtained by mail by calling CBER at 1– 

800–835–4709 or 240–402–8010. See 

the SUPPLEMENTARY INFORMATION section 

for electronic access to the draft 

guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Vishal Bhatnagar, Oncology Center of 

Excellence, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 22, Rm. 2113, Silver Spring, 

MD 20993–0002, 240–402–3696; or 

Janice Kim, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 22, Rm. 2329, Silver Spring, 

MD 20993–0002, 301–796–9628; or 

Stephen Ripley, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 7301, 

Silver Spring, MD 20993–0002, 240– 

402–7911. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Core Patient-Reported Outcomes in 

Cancer Clinical Trials.’’ This draft 

guidance provides recommendations to 

sponsors regarding the collection of a 

core set of PROs in cancer clinical trials 

and related considerations for 

instrument selection and trial design. 

Although this draft guidance focuses on 

PRO measures, some of the 

recommendations may be relevant to 

other clinical outcome assessments (i.e., 

clinician-reported outcome, observerreported outcome, performance 

outcome) in cancer clinical trials. The 

draft guidance is specific to registration 

trials for anti-cancer therapies intended 

to demonstrate an effect on survival, 

tumor response, or delay in the 

progression of a malignancy. 

Cancer clinical trials typically employ 

standardized efficacy assessment using 

overall survival and tumor measures, 

and safety assessments provided by 

clinician reporting of adverse events. 

FDA acknowledges the potential added 

value of incorporating PRO 

measurement of symptoms and 

functional impacts into the benefit/risk 

assessment in appropriately designed 

trials; however, heterogeneity in PRO 

assessment strategies has lessened the 

regulatory utility of PRO data from 

cancer trials. Systematic assessment of a 

core set of PROs can facilitate high 

quality data on patient-reported 

symptoms and functional impacts. FDA 

has previously described a core set of 

PROs that may be important 

contributors to a patient’s health-related 

quality of life and that may be sensitive 

to the effect of the disease and treatment 

under study.1

FDA is issuing this draft guidance to 

provide FDA’s current thinking on the 

core PROs, considerations for 

instrument selection to measure the core 

PROs, trial design considerations such 

as assessment frequency, and labeling 

considerations. The core PROs 

recommended in the draft guidance are 

disease-related symptoms, symptomatic 

adverse events, overall side effect 

impact summary measure, physical 

function, and role function. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the current thinking of FDA 

on ‘‘Core Patient-Reported Outcomes in 

Cancer Clinical Trials.’’ It does not 

establish any rights for any person and 

is not binding on FDA or the public. 

You can use an alternative approach if 

it satisfies the requirements of the 

applicable statutes and regulations. 

II. Paperwork Reduction Act of 1995 

While this guidance contains no 

collection of information, it does refer to 

previously approved FDA collections of 

information. Therefore, clearance by the 

Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act of 1995 (PRA) (44 U.S.C. 3501– 

3521) is not required for this guidance. 

The previously approved collections of 

information are subject to review by 

OMB under the PRA. The collections of 

information in 21 CFR part 312 have 

been approved under OMB control 

number 0910–0014; the collections of 

information in 21 CFR part 314 have 

been approved under OMB control 

number 0910–0001; and the collections 

of information in 21 CFR part 601 have 

been approved under 0910–0338. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at either 

https://www.fda.gov/drugs/guidancecompliance-regulatory-information/ 

guidances-drugs, https://www.fda.gov/ 

vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics/biologics-guidances, or https:// 

www.regulations.gov. 

Dated: June 4, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–12166 Filed 6–9–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2019–E–5832] 

Determination of Regulatory Review 

Period for Purposes of Patent 

Extension; XPOVIO 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or the Agency) has 

determined the regulatory review period 

for XPOVIO and is publishing this 

notice of that determination as required 


khammond on DSKJM1Z7X2PROD with NOTICES
30946 Federal Register / Vol. 86, No. 110 / Thursday, June 10, 2021 / Notices 

by law. FDA has made the 

determination because of the 

submission of an application to the 

Director of the U.S. Patent and 

Trademark Office (USPTO), Department 

of Commerce, for the extension of a 

patent which claims that human drug 

product. 

DATES: Anyone with knowledge that any 

of the dates as published (see the 

SUPPLEMENTARY INFORMATION section) are 

incorrect may submit either electronic 

or written comments and ask for a 

redetermination by August 9, 2021. 

Furthermore, any interested person may 

petition FDA for a determination 

regarding whether the applicant for 

extension acted with due diligence 

during the regulatory review period by 

December 7, 2021. See ‘‘Petitions’’ in 

the SUPPLEMENTARY INFORMATION section 

for more information. 

ADDRESSES: You may submit comments 

as follows. Please note that late, 

untimely filed comments will not be 

considered. Electronic comments must 

be submitted on or before August 9, 

2021. The https://www.regulations.gov 

electronic filing system will accept 

comments until 11:59 p.m. Eastern Time 

at the end of August 9, 2021. Comments 

received by mail/hand delivery/courier 

(for written/paper submissions) will be 

considered timely if they are 

postmarked or the delivery service 

acceptance receipt is on or before that 

date. 

Electronic Submissions 

Submit electronic comments in the 

following way: 

• Federal eRulemaking Portal: 

https://www.regulations.gov. Follow the 

instructions for submitting comments. 

Comments submitted electronically, 

including attachments, to https://

www.regulations.gov will be posted to 

the docket unchanged. Because your 

comment will be made public, you are 

solely responsible for ensuring that your 

comment does not include any 

confidential information that you or a 

third party may not wish to be posted, 

such as medical information, your or 

anyone else’s Social Security number, or 

confidential business information, such 

as a manufacturing process. Please note 

that if you include your name, contact 

information, or other information that 

identifies you in the body of your 

comments, that information will be 

posted on https://www.regulations.gov. 

• If you want to submit a comment 

with confidential information that you 

do not wish to be made available to the 

public, submit the comment as a 

written/paper submission and in the 

manner detailed (see ‘‘Written/Paper 

Submissions’’ and ‘‘Instructions’’). 

Written/Paper Submissions 

Submit written/paper submissions as 

follows: 

• Mail/Hand Delivery/Courier (for 

written/paper submissions): Dockets 

Management Staff (HFA–305), Food and 

Drug Administration, 5630 Fishers 

Lane, Rm. 1061, Rockville, MD 20852. 

• For written/paper comments 

submitted to the Dockets Management 

Staff, FDA will post your comment, as 

well as any attachments, except for 

information submitted, marked and 

identified, as confidential, if submitted 

as detailed in ‘‘Instructions.’’ 

Instructions: All submissions received 

must include the Docket No. FDA– 

2019–E–5832 for ‘‘Determination of 

Regulatory Review Period for Purposes 

of Patent Extension; XPOVIO.’’ Received 

comments, those filed in a timely 

manner (see ADDRESSES), will be placed 

in the docket and, except for those 

submitted as ‘‘Confidential 

Submissions,’’ publicly viewable at 

https://www.regulations.gov or at the 

Dockets Management Staff between 9 

a.m. and 4 p.m., Monday through 

Friday, 240–402–7500. 

• Confidential Submissions—To 

submit a comment with confidential 

information that you do not wish to be 

made publicly available, submit your 

comments only as a written/paper 

submission. You should submit two 

copies total. One copy will include the 

information you claim to be confidential 

with a heading or cover note that states 

‘‘THIS DOCUMENT CONTAINS 

CONFIDENTIAL INFORMATION.’’ The 

Agency will review this copy, including 

the claimed confidential information, in 

its consideration of comments. The 

second copy, which will have the 

claimed confidential information 

redacted/blacked out, will be available 

for public viewing and posted on 

https://www.regulations.gov. Submit 

both copies to the Dockets Management 

Staff. If you do not wish your name and 

contact information to be made publicly 

available, you can provide this 

information on the cover sheet and not 

in the body of your comments and you 

must identify this information as 

‘‘confidential.’’ Any information marked 

as ‘‘confidential’’ will not be disclosed 

except in accordance with § 10.20 (21 

CFR 10.20) and other applicable 

disclosure law. For more information 

about FDA’s posting of comments to 

public dockets, see 80 FR 56469, 

September 18, 2015, or access the 

information at: https://

www.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, go to https://

www.regulations.gov and insert the 

docket number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Dockets Management 

Staff, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

FOR FURTHER INFORMATION CONTACT: 

Beverly Friedman, Office of Regulatory 

Policy, Food and Drug Administration, 

10903 New Hampshire Ave., Bldg. 51, 

Rm. 6250, Silver Spring, MD 20993, 

301–796–3600. 

SUPPLEMENTARY INFORMATION: 

I. Background 

The Drug Price Competition and 

Patent Term Restoration Act of 1984 

(Pub. L. 98–417) and the Generic 

Animal Drug and Patent Term 

Restoration Act (Pub. L. 100–670) 

generally provide that a patent may be 

extended for a period of up to 5 years 

so long as the patented item (human 

drug product, animal drug product, 

medical device, food additive, or color 

additive) was subject to regulatory 

review by FDA before the item was 

marketed. Under these acts, a product’s 

regulatory review period forms the basis 

for determining the amount of extension 

an applicant may receive. 

A regulatory review period consists of 

two periods of time: A testing phase and 

an approval phase. For human drug 

products, the testing phase begins when 

the exemption to permit the clinical 

investigations of the drug becomes 

effective and runs until the approval 

phase begins. The approval phase starts 

with the initial submission of an 

application to market the human drug 

product and continues until FDA grants 

permission to market the drug product. 

Although only a portion of a regulatory 

review period may count toward the 

actual amount of extension that the 

Director of USPTO may award (for 

example, half the testing phase must be 

subtracted as well as any time that may 

have occurred before the patent was 

issued), FDA’s determination of the 

length of a regulatory review period for 

a human drug product will include all 

of the testing phase and approval phase 

as specified in 35 U.S.C. 156(g)(1)(B). 

FDA has approved for marketing the 

human drug product, XPOVIO 

(selinexor) indicated in combination 

with dexamethasone for the treatment of 

adult patients with relapsed or 

refractory multiple myeloma who have 

received at least four prior therapies and 

whose disease is refractory to at least 


khammond on DSKJM1Z7X2PROD with NOTICES
Federal Register / Vol. 86, No. 110 / Thursday, June 10, 2021 / Notices 30947 

two proteasome inhibitors, at least two 

immunomodulatory agents, and an antiCD38 monoclonal antibody. This 

indication is approved under 

accelerated approval based on response 

rate. Continued approval for this 

indication may be contingent upon 

verification and description of clinical 

benefit in a confirmatory trial. 

Subsequent to this approval, the USPTO 

received a patent term restoration 

application for XPOVIO (U.S. Patent No. 

8,999,996) from Karyopharm 

Therapeutics Inc., and the USPTO 

requested FDA’s assistance in 

determining the patent’s eligibility for 

patent term restoration. In a letter dated 

January 21, 2020, FDA advised the 

USPTO that this human drug product 

had undergone a regulatory review 

period and that the approval of XPOVIO 

represented the first permitted 

commercial marketing or use of the 

product. Thereafter, the USPTO 

requested that FDA determine the 

product’s regulatory review period. 

II. Determination of Regulatory Review 

Period 

FDA has determined that the 

applicable regulatory review period for 

XPOVIO is 2,585 days. Of this time, 

2,253 days occurred during the testing 

phase of the regulatory review period, 

while 332 days occurred during the 

approval phase. These periods of time 

were derived from the following dates: 

1. The date an exemption under 

section 505(i) of the Federal Food, Drug, 

and Cosmetic Act (FD&C Act) (21 U.S.C. 

355(i)) became effective: June 6, 2012. 

The applicant claims June 8, 2012, as 

the date the investigational new drug 

application (IND) became effective. 

However, FDA records indicate that the 

IND effective date was June 6, 2012, 

which was the first date after receipt of 

an earlier IND that the investigational 

studies were allowed to proceed. 

2. The date the application was 

initially submitted with respect to the 

human drug product under section 505 

of the FD&C Act: August 6, 2018. The 

applicant claims August 5, 2018, as the 

date the new drug application (NDA) for 

XPOVIO (NDA 212306) was initially 

submitted. However, FDA records 

indicate that NDA 212306 was 

submitted on August 6, 2018. 

3. The date the application was 

approved: July 3, 2019. FDA has verified 

the applicant’s claim that NDA 212306 

was approved on July 3, 2019. 

This determination of the regulatory 

review period establishes the maximum 

potential length of a patent extension. 

However, the USPTO applies several 

statutory limitations in its calculations 

of the actual period for patent extension. 

In its application for patent extension, 

this applicant seeks 291 days of patent 

term extension. 

III. Petitions 

Anyone with knowledge that any of 

the dates as published are incorrect may 

submit either electronic or written 

comments and, under 21 CFR 60.24, ask 

for a redetermination (see DATES). 

Furthermore, as specified in § 60.30 (21 

CFR 60.30), any interested person may 

petition FDA for a determination 

regarding whether the applicant for 

extension acted with due diligence 

during the regulatory review period. To 

meet its burden, the petition must 

comply with all the requirements of 

§ 60.30, including but not limited to: 

must be timely (see DATES), must be 

filed in accordance with § 10.20, must 

contain sufficient facts to merit an FDA 

investigation, and must certify that a 

true and complete copy of the petition 

has been served upon the patent 

applicant. (See H. Rept. 857, part 1, 98th 

Cong., 2d sess., pp. 41–42, 1984.) 

Petitions should be in the format 

specified in 21 CFR 10.30. 

Submit petitions electronically to 

https://www.regulations.gov at Docket 

No. FDA–2013–S–0610. Submit written 

petitions (two copies are required) to the 

Dockets Management Staff (HFA–305), 

Food and Drug Administration, 5630 

Fishers Lane, Rm. 1061, Rockville, MD 

20852. 

Dated: June 3, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–12167 Filed 6–9–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket Nos. FDA–2020–E–1325 and FDA– 

2020–E–1324] 

Determination of Regulatory Review 

Period for Purposes of Patent 

Extension; WAKIX 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) has 

determined the regulatory review period 

for WAKIX and is publishing this notice 

of that determination as required by 

law. FDA has made the determination 

because of the submission of 

applications to the Director of the U.S. 

Patent and Trademark Office (USPTO), 

Department of Commerce, for the 

extension of a patent which claims that 

human drug product. 

DATES: Anyone with knowledge that any 

of the dates as published (see 

SUPPLEMENTARY INFORMATION) are 

incorrect may submit either electronic 

or written comments and ask for a 

redetermination by August 9, 2021. 

Furthermore, any interested person may 

petition FDA for a determination 

regarding whether the applicant for 

extension acted with due diligence 

during the regulatory review period by 

December 7, 2021. See ‘‘Petitions’’ in 

the SUPPLEMENTARY INFORMATION section 

for more information. 

ADDRESSES: You may submit comments 

as follows. Please note that late, 

untimely filed comments will not be 

considered. Electronic comments must 

be submitted on or before August 9, 

2021. The https://www.regulations.gov 

electronic filing system will accept 

comments until 11:59 p.m. Eastern Time 

at the end of August 9, 2021. Comments 

received by mail/hand delivery/courier 

(for written/paper submissions) will be 

considered timely if they are 

postmarked or the delivery service 

acceptance receipt is on or before that 

date. 

Electronic Submissions 

Submit electronic comments in the 

following way: 

• Federal eRulemaking Portal: 

https://www.regulations.gov. Follow the 

instructions for submitting comments. 

Comments submitted electronically, 

including attachments, to https://

www.regulations.gov will be posted to 

the docket unchanged. Because your 

comment will be made public, you are 

solely responsible for ensuring that your 

comment does not include any 

confidential information that you or a 

third party may not wish to be posted, 

such as medical information, your or 

anyone else’s Social Security number, or 

confidential business information, such 

as a manufacturing process. Please note 

that if you include your name, contact 

information, or other information that 

identifies you in the body of your 

comments, that information will be 

posted on https://www.regulations.gov. 

• If you want to submit a comment 

with confidential information that you 

do not wish to be made available to the 

public, submit the comment as a 

written/paper submission and in the 

manner detailed (see ‘‘Written/Paper 

Submissions’’ and ‘‘Instructions’’). 

Written/Paper Submissions 

Submit written/paper submissions as 

follows: 


khammond on DSKJM1Z7X2PROD with NOTICES