August 2020 decisions expected from the FDA

At Prime Therapeutics (Prime), we’ve positioned ourselves to best prepare our clients to manage the new drugs that come on the market. Our clinical and trade relations teams keep a keen eye on drugs likely to be approved by the U.S. Food and Drug Administration (FDA).

8/1/2020: belantamab mafodotin

The FDA has granted priority review of GlaxoSmithKline’s belantamab mafodotin for the treatment of relapsed or refractory multiple myeloma in patients, whose prior therapy included an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. Belantamab mafodotin is an antibody-drug conjugate that targets B-cell maturation antigen (BCMA), a cell surface receptor that presents on almost all multiple myeloma cells. If approved, belantamab mafodotin will become the first available anti-BCMA treatment. GSK submitted belantamab mafodotin’s application based on clinical trial DREAMM-2, which demonstrated that belantamab mafodotin 2.5mg/kg achieved an overall response rate (ORR) of 31% and belantamab mafodotin 3.4mg/kg achieved an ORR of 34%. The median duration of response without disease progression was 2.9 months for the lowest dose and 4.9 months for the highest dose.¹ GSK is conducting additional studies to test belantamab mafodotin in combination with standard and new treatments in myeloma patients who have previously failed one or two prior lines of therapy. Similar products are dependent on each individual patient and their prior treatments.

8/1/2020: satralizumab

The FDA is reviewing Roche’s satralizumab for treatment of neuromyelitis optica spectrum disorder (NMOSD). NMOSD is an autoimmune disease of the central nervous system that primarily damages the optic nerves and spinal cord. It is commonly associated with pathogenic antibodies (AQP4-IgG) that target and damage astrocytes. AQP4-IgG antibodies are detectable in about two thirds of NMOSD patients. Roche is seeking approval based on two Phase 3 studies, SAkuraStar and SAkuraSky, which evaluated the safety and efficacy of satralizumab as a monotherapy and in combination with baseline immunosuppressant therapy. SAkuraStar study demonstrated satralizumab monotherapy achieved a 55% reduction in the risk of relapses compared to placebo in the overall study population of aquaporin-4 antibody (AQP4-IgG) seropositive and seronegative patients. The overall satralizumab-treated population also showed 76.1% of patients were relapse-free at 48 weeks, and 72.1% were relapse free at 96 weeks compared to 61.9% and 51.2% with placebo.² SAKuraSky demonstrated a 62% in reduction in the risk of relapses compared to placebo in the overall study population when combined with baseline immunosuppressant therapies. In the satralizumab-treated population, 88.9% were relapse-free at 48 weeks and 77.6% were relapse-free at 96 weeks compared to 66% and 58.7% with placebo.² In May 2020, Roche published its data from the an open label extension data from both studies that  reinforced satralizumab was well-tolerated as a monotherapy or in combination with baseline immunosuppressive therapy in patients with NMOSD.³ Additionally, when treated with the same dose and frequency of satralizumab, adolescent results were consistent with adults. Similar products include Alexion Pharmacetucals’ Soliris® (eculizumab) and Viela Bio’s Uplinza® (inebilizumab-cdon).

8/5/2020: Viaskin Peanut

DBV Technologies’ Viaskin Peanut is requesting approval from the FDA for children ages four to eleven with a peanut allergy. Viaskin Peanut is a non-invasive, once-daily patch that delivers microgram quantities of peanut that activates the immune system. DBV Technologies is seeking approval based on a Phase 3 clinical trial, PEPITES, which demonstrated statistical significance with 35.3% of patients responding to Viaskin Peanut 250 micrograms after 12 months of treatment compared to 13.6% of patients in the placebo arm. The primary endpoint, which evaluates the 95% confidence interval (CI) in the difference in response rate between the active and placebo arms, did not reach the 15% lower bound of the CI that was proposed in the study.⁴ In March 2020, the FDA identified questions regarding efficacy and patch-site adhesion therefore delaying PDUFA date till August 2020. DBV Technologies is currently conducting a Phase 3 trial for patients ages one to three, and Phase 2 trial for adolescents and adults. Additionally, DBV Technologies is using their patch technology for development of two more products; a milk allergy patch, and an egg allergy patch, both which are still in clinical phases. Similar treatments for peanut allergy would include Aimmune therapeutics’ Palforzia^® (peanut (arachia hypogaea) allergen powder-dnfp) and peanut avoidance.

8/7/2020: Olinvo™ (oliceridine) Injection

Trevena’s Olinvo is being reviewed by the FDA for the management of moderate-to-severe acute pain in hospital and similar settings. Trevena hopes to use Olinvo to replace intravenous opioid analgesics, claiming Olinvo was designed to deliver the pain relief of IV opioid, but with fewer adverse effects due to its biased ligand mechanism of action. In November 2018 Olinvo received a complete response letter (CRL) asking for additional safety data. In February 2020, Trevena resubmitted Olinvo to the FDA citing 27mg as a maximum daily dose.⁵ Trevena anticipates Olinvo to be scheduled by the U.S. Drug Enforcement Administration (DEA) as a Schedule II controlled substance. Similar products include morphine and its generic versions.

8/10/2020: KTE-X19

The FDA is reviewing Kite’s second cellular therapy, KTE-X19, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL). Like Kite’s already approved Yescarta^® (axicabtagene ciloleucel), KTE-X19 is an anti-CD19 CAR-T therapy. The difference stems from the manufacturing process; KTE-X19 has T-cell selection and lymphocyte enrichment that Kite believes will be suitable for use in B-cell malignancies with circulating lymphoblasts. Kite is seeking approval based on the Phase 2, ZUMA-2 trial, which showed that 93% of patients responded to a single infusion of KTE-X19, including 67% percent of patients achieving a complete response.⁶ Similar products include BeiGene’s Brukinsa^® (zanubrutinib) and Janssen’s Imbruvica® (ibrutinib).

Fennec Pharmaceuticals’ Pedmark has been granted priority review from the FDA for prevention of ototoxicity induced by cisplatin chemotherapy in pediatric patients one month to <18 years of age with localized, non-metastatic solid tumors. Platinum-induced ototoxicity is permanent and irreversible. Pedmark’s application is based on two Phase 3 clinical trials, SIOPEL 6 and ACCL0431, which evaluated survival and reduction of ototoxicity in patients being treated with cisplatin. SIOPEL concluded that the addition of sodium thiosulfate to cisplatin significantly reduces the incidence of cisplatin-induced hearing loss without any evidence of tumor protection. Hearing loss occurred in 63% of patients with cisplatin and 32% of patients with cisplatin plus sodium thiosulfate.⁷ ACCL0431 drew similar conclusions in pediatric population. Hearing loss occurred in 56.4% taking cisplatin alone compared to 28.6% of patients treated with cisplatin plus sodium thiosulfate. Currently there are no preventive agents for this condition. Previous treatment for ototoxicity induced by cisplatin chemotherapy has been a cochlear (inner ear) implant.

8/21/2020: Roctavian™ (valoctocogene roxaparvovec)

The FDA has granted priority review of BioMarin’s Roctavian, as a gene therapy treatment for severe hemophilia A. Roctavian uses adeno-associated virus (AAV) vectors to deliver a functional copy of factor VIII that patients with hemophilia A are missing. Preliminary results from nine patients were published in 2017. At the end of the first, second and third years, post-infusion, mean Factor VIII activity level of the high dose 6e13 vg/kg cohort was 64.3, 36.4 and 32.7 IU/dL respectively as measured by the CS assay. BioMarin just released results at the four-year mark, in which the mean Factor VIII levels fell to 24.2 IU/dL.⁸ A Phase 3 clinical trial evaluating safety and effectiveness of Roctavian in hemophilia A patients who have factor VIII levels of less than 1IU/dL and who have received prophylactic factor VIII infusions is underway and expected to be completed by September 2023. BioMarin has indicated this single-use therapy will be priced anywhere from $2 million to $3 million for Roctavian. Pfizer/Sangamo Therapeutics has their rival gene therapy agent, SB-525, for treatment of hemophilia A in clinical trials, that if approved, will directly compete with Roctavian. Similar products include Factor VIII products.

8/22/2020: veverimer

The FDA is reviewing Tricida’s veverimer for treatment of metabolic acidosis in patients with chronic kidney disease (CKD). Veverimer is administered orally as a counterion-free, non-absorbed polymer that selectively binds hydrochloric acid in the gastrointestinal tract, which results in a rise in serum bicarbonate. This contrasts with alkali supplements that neutralize acid. In a Phase 3 clinical trial veverimer demonstrated improved quality of life and physical function when compared to placebo. At week 52, researchers found 64% of patients taking veverimer had an average of a 4mEq/L increase in serum bicarbonate vs. 38% in placebo patients. Patients taking veverimer had a 12.5-point improvement in physical functioning (measured by walking several blocks or climbing a flight of stairs) when compared with 0.3-point improvement for placebo patients.⁹ If approved, veverimer is expected to be available in late September. Similar products include sodium bicarbonate or sodium citrate.

8/24/2020: risdiplam

The FDA has granted priority review to Genentech’s risdiplam for treatment of spinal muscular atrophy (SMA). Risdiplam is an at home, orally administered liquid that works as a survival motor neuron-2 (SMN-2) splicing modifier for SMA. The FDA granted risdiplam orphan drug and fast track designations.  Genentech’s application is based on data from pivotal trial FIREFISH with supporting trials SUNFISH, JEWELFISH and RAINBOWFISH. The FIREFISH trial evaluated dose-escalation in infants with SMA type 1 and assessed safety.  FIREFISH demonstrated a significant increase in achieved motor milestones in infants with Type 1 spinal muscular atrophy aged one to seven months after 12 months of treatment. It met its primary endpoint with 29% of the infants sitting without support for five seconds by month 12, as assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III).¹⁰ Risdiplam is currently conducting additional studies with patients ranging from newborn to 60 years old including patients previously treated with other SMA therapies. Similar products include AveXis’ Zolgensma^® (onasemnogene abeparvovec-xioi) which is approved for children less than two years old with SMA 1 and Biogen’s Spinraza^® (nusinersen) which is approved to treat all forms of SMA.

8/27/2020: Winlevi™ (clascoterone)

Cassiopea SPA’s Winlevi is being reviewed by the FDA for treatment of acne. Winlevi is a new topical anti-androgen treatment which works on hormones that can lead to skin lesions. According to Cassiopea SPA’s Phase 3 trial, 57% of acne patients had at least a two-step improvement resulting in either clear or almost clear faces after 52 weeks.¹¹ The study also recorded a two-step improvement on the trunk resulting in a zero or one Investigator Global Assessment (IGA) score for 62% of participants at week 52. Similar products include Almirall’s Aczone^® (dapsone) and generics.

8/28/2020: Tlando™ (testosterone undecanoate)

Lipocine’s Tlando is being reviewed by the FDA as an oral, twice-daily, fixed-dose testosterone replacement therapy for men with hypogonadism. On January 10, 2018, the FDA AdCom voted 13-6 against approval of Tlando.¹² On May 9, 2018, the FDA issued a complete response letter (CRL) which included four deficiencies:

• Confirming the reliability of testosterone data
• Obtaining definitive preapproval evidence
• Verifying reliability of Cmax secondary endpoints of Tlando and
• Determining appropriate stopping criteria¹³

Tlando was previously seeking approval in November 2019, however was issued an additional CRL from the FDA. The CRL identified that the efficacy trial did not meet the three secondary endpoints for maximal testosterone concentrations.¹⁴ Similar products include testosterone topicals and Clarus’ oral Jatenzo™ (testosterone undecanoate). Compared with topical testosterone products, oral testosterone products are not required by the FDA to include a boxed warning relating to testosterone transference.¹⁴ On April 3, 2019, Lipocine filed an injunction against Clarus’ Jatenzo for infringement on six of Lipocine’s U.S patents.¹⁵ Sales for male testosterone products in the U.S. were $1.7 billion in 2018 and there were approximately 7.2 million prescriptions in 2018.¹⁶

8/30/2020: tafasitamab

The FDA has granted priority review of MorphoSys AG’s tafasitamab in combination with Celgene’s Revlimid® (lenalidomide) for treatment of relapsed/refractory diffuse large B cell lymphoma (r/r DLBCL). Tafasitamab is a humanized monoclonal antibody directed against CD19. Similar products included two CAR-T therapies Kite’s Yescarta® (axicabtagene ciloleucel) and Novartis’ Kymriah^® (tisagenlecleucel). Unlike the two CAR-T therapies, which require an elaborate personalized manufacturing process (cells are isolated from the patient, manipulated in the lab by adding chimeric antigen receptors to direct T-cells to find cancer cells and then re-infused into the patient), tafasitamab is looking to be an “off the shelf cell therapy.” The submission of tafasitamab was based on the primary analysis data from the L-MIND trial, which evaluated the efficacy and safety of tafasitamab plus lenalidomide. The overall response rate (ORR) was 58% per independent review committee, including a 33% complete response rate and a 35% partial response rate.17 The progression-free survival (PFS) rate was 16.2 months with tafasitamab. Tafasitamab is currently conducting retrospective cohort study RE-MIND and continuing ongoing L-MIND trials.

The drug pipeline is full of new drugs that may help members feel better and live well. Prime drug pipeline tracking helps keep you on top of drug trends, because it’s easier to manage change when you can see it coming.

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While the information in this newsletter is from sources we believe to be reliable, we do not warrant that the information in this document is free from error. Use it only as a guide. Statements regarding drugs or manufacturers are not intended as promotion; those statements should not be used to make assumptions about formulary status. Each trademarked drug name is the property of its respective owner.

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References

1. https://www.targetedonc.com/view/fda-grants-priority-review-to-belantamab-mafodotin-for-relapsedrefractory-multiple-myeloma
2. https://www.roche.com/media/releases/med-cor-2019-10-30.htm
3. https://www.businesswire.com/news/home/20200521005824/en/New-Longer-Term-Data-Reinforce-Safety-Genentech%E2%80%99s-Satralizumab
4. https://www.dbv-technologies.com/wp-content/uploads/2018/03/pr-pepites-topline-results-final.pdf
5. https://www.trevena.com/investors/press-releases/detail/224/trevena-resubmits-new-drug-application-for-oliceridine
6. https://www.gilead.com/news-and-press/press-room/press-releases/2020/2/us-fda-grants-priority-review-for-kites-ktex19-biologics-license-application-bla-in-relapsed-or-refractory-mantle-cell-lymphoma
7. https://fennecpharma.com/product-candidates/pedmark/clinical-trials/
8. https://endpts.com/biomarin-spells-out-a-troubling-plunge-in-factor-viii-levels-for-its-big-blockbuster-contender/
9. https://www.healio.com/news/nephrology/20200328/veverimer-demonstrates-benefits-in-metabolic-acidosis-for-patients-with-ckd-diabetes
10. https://www.gene.com/media/press-releases/14836/2020-02-06/genentechs-risdiplam-showed-significant-
11. https://www.cosmopharma.com/news-and-media/press-releases-and-company-news/2018/100710
12. https://www.fda.gov/media/111411/download
13. https://www.benzinga.com/general/biotech/18/05/11675456/lipocines-regulatory-hiccups-continue-testosterone-drug-issued-comple?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A%20benzinga%20%28Benzinga%20News%20Feed%29
14. https://www.prnewswire.com/news-releases/lipocine-receives-complete-response-letter-for-tlando-from-us-fda-300955195.html#:~:text=TLANDO%2C%20a%20novel%20oral%20prodrug,Administration%20on%20November%208%2C%202019.https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/testosterone-information
15. https://www.prnewswire.com/news-releases/lipocine-announces-tlando-nda-pdufa-action-date-of-november-9-2019-300849400.html
16. https://www.lipocine.com/pipeline/tlando/
17. https://www.targetedonc.com/view/fda-accepts-bla-and-grants-priority-review-to-tafasitamablenalidomide-in-rr-dlbcl